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PRINCIPLES  OF 
HUMAN  PHYSIOLOGY 


PRINCIPLES  OF 
HUMAN  PHYSIOLOGY 


BY 


ERNEST    H.    STARLING 

M.D.  (Lond.),  F.R.C.P.,  F.R.S.,  Hon.  M.D.  (Breslau) 

Jodrell  Professor  of  Physiology  in  University 
College,  London 


LEA    &    FEBIGER 

PHILADELPHIA   AND    NEW    YORK 

1912 


Printed  in  Great  Britain 


(■  I 


PREFACE 


Physiology,  though  dealing  with  the  phenomena  of  Hving  organisms, 
has  to  use  the  same  tools,  whether  material  or  intellectual,  as  the 
sciences  of  physics  and  chemistry.  Any  advances  which  are  made 
in  these  sciences  not  only  increase  our  powers  of  attack  upon  physio- 
logical problems  but  at  the  same  time  alter  the  intellectual  standpoint 
from  which  we  view  them.  On  the  other  hand,  the  investigation  of  the 
phenomena  of  living  beings  is  continually  attracting  our  attention 
and  that  of  workers  in  the  other  branches  of  science  to  unexplored 
regions  in  physics  and  chemistry.  This  mutual  stimulation  and  co- 
operation among  the  different  sciences  have  as  their  result  a  continual 
modification  of  our  attitude  with  regard  to  the  fundamental  problems 
of  physiology.  The  present  time  has  seemed  to  me,  therefore,  fitting 
for  the  production  of  a  textbook  which,  while  not  neglecting  the  data 
of  physiology,  should  lay  special  stress  on  the  significance  of  these 
data,  and  attempt  to  weave  them  into  a  fabric  representing  the  prin- 
ciples which  are  guiding  physiologists  and  physicians  of  the  present 
day  in  their  endeavours  to  extend  the  bounds  of  the  known  and  to 
increase  their  powers  of  control  over  the  functions  of  living  organisms. 

In  a  science  such  as  physiology,  based  on  so  wide  a  discipline  and 
with  so  diverse  a  technique,  it  is  almost  impossible  for  any  one  man 
to  attain  to  a  personal  acquaintance  with  all  its  branches.  In  the 
present  book  I  have  therefore  not  hesitated  to  avail  myself  of  the 
work  of  masters  of  the  science  in  fields  which  I  had  not  myself  explored. 
Thus,  in  the  physiology  of  the  nervous  system,  which  has  been  trans- 
formed and  built  up  on  a  new  basis  by  the  researches  of  Sherrington,  I 
have  endeavoured  to  follow  this  author  as  closely  as  possible.  I  am 
also  deeply  sensible  of  my  obhgations  to  the  writings  of  Tigerstedt, 
Leathes,  and  Lusk  on  general  metabolism,  of  Abderhalden  and 
Plinamer  on  physiological  chemistry,  of  Bayliss  on  general  physiology, 
as  well  as  to  various  authors  of  articles  in  the  "  Ergebnisse  der 
Physiologie,"  in  Nagel's  ''  Handbuch  der  Physiologie,"  and  in  Dr. 
L.  E.  Hill's  "  Recent  and  Further  Advances  in  Physiology." 

Although  I  have  endeavoured  to  confine  my  demands  on  the 
previous  knowledge  of  the  student  within  the  narrowest  possible 
limits,  I  should  recommend  hinx  in  every  case  to  read  some  primer 
on  physiology  in  order  to  obtain  a  bird's-eye  view  of  the  subject 


vi  PREFACE 

before  beginning  the  study  of  this  work.  He  will  then  be  able  to  vary 
the  order  of  chapters  in  this  book  according  to  the  part  of  physiology 
which  he  is  hearing  about  in  his  lectures  or  working  at  in  his  practical 
classes.  Those  of  my  readers  who  are  entirely  unacquainted  with 
physiology  might  do  well  on  a  first  perusal  to  omit  Book  I.,  deaUng 
with  the  general  concepts  of  the  science. 

I  have  deemed  it  a  hopeless  and  indeed  a  useless  task  to  give  any 
full  account  of  the  multifarious  methods  employed  in  the  experimental 
investigation  of  the  different  organs  of  the  body.  In  most  cases  I 
have  consigned  to  small  type  a  description  of  one  or  two  typical 
methods,  which  would  sufS.ce  to  show  how  the  questions  may  be 
approached  from  the  experimental  side. 

Throughout  the  work  I  have  sought  to  show  that  the  only  founda- 
tion for  rational  therapeutics  is  the  proper  understanding  of  the 
working  of  the  healthy  body.  Until  we  know  more  about  the  physio- 
logy of  nutrition,  quacks  will  thrive  and  food  faddists  abound.  Igno- 
rance of  physiology  tends  to  make  a  medical  man  as  credulous  as  his 
patients  and  aknost  as  easily  beguiled  by  the  specious  puffings  of  the 
advertising  druggist.  I  trust,  therefore,  that  the  following  pages 
will  be  found  of  value  not  only  to  the  candidate  for  a  university 
degree  but  also  to  the  practitioner  of  medicine  in  equipping  him  for 
his  struggle  against  the  factors  of  disease. 

In  the  selection  of  diagrams  for  the  illustration  of  this  book  I 
am  especially  indebted  to  Professor  Schafer  and  to  his  publishers, 
Messrs.  Longmans,  for  the  permission  to  make  use  of  a  large  number 
from  Quain's  "  Anatomy  "  and  from  Schafer's  "  Essentials  of  His- 
tology." I  must  also  express  my  obligation  to  Professor  Wilson  for 
the  use  of  certain  figures  from  his  admirable  work  on  the  cell,  to 
the  publishers  of  Cunningham's  "  Anatomy,"  and  to  many  physio- 
logical friends,  especially  to  Dr.  Mott  and  Dr.  Gordon  Holmes,  for  the 
use  of  original  diagrams.      The  index  was  kindly  made  for  me  by 

Mr.  Lovatt  Evans. 

ERNEST  H.  STARLING 

University  College,  London 
May  1912 


CONTENTS 


CHAPTER  I 
INTRODUCTION  1 

BOOK  I 
GENERAL   PHYSIOLOGY 

CHAPTER  II 
THE  STRUCTURAL  BASIS  OF  THE  BODY  13 

CHAPTER  III 
THE  MATERIAL  BASIS  OF  THE  BODY 

SECTION 

I.  The  Elementary  Constituents  of  Living  Cells  39 

II.  The  Proximate  Constituents  of  the  Anevlal  Body  49 

III.  The  Fats  58 

rV.  The  Carbohydrates  64 

V.  The  Proteins  78 

VI.  The  Mechanism  of  Organic  Synthesis  121 

CHAPTER  IV 

THE  ENERGETIC  BASIS  OF  THE  BODY 

I.  The  Energy  op  Molecules  in  Solution  1 30 

II.  The  Passage  of  Water  and   Dissolved  Substances  across 

Membranes  145 

III.  The  Properties  of  Colloids  154 

rV.  The    Mechanism    of    Chemical   Changes  in    Living    Matter. 

Ferments  170 

V.  Electrical  Changes  in  Living  Tissues  189 

BOOK  IT 

THE  MECHANISMS  OF  MOVEMENT  AND  SENSATION 
« 

CHAPTER  V 

THE  CONTRACTILE  TISSUES 

I.  The  Structure  OF  Voluntary  Muscle  107 

II.  The  Excitation  of  Muscle  -<•«■> 
III.  The  Mechanical  Changes  that  a  Muscle  undkhooks  wmkn  it 

Contracts  215 


X  CONTENTS 

CHAPTER  X  [continued) 
INTESTINAL  DIGESTION 

SECTION  PAGE 

V.  The  Panckeatic  Juice  788 

VI.  The  Bile  803 

VII.  Ftjnctions  of  the  Large  Intestine  813 

VIII.  Movements  of  the  Intestines  817 

IX.  The  Absorption  of  the  Food -stuffs  827 

X.  The  F^ces  851 


CHAPTER  XI 

THE  HISTORY  OF  THE  FOOD-STUFFS 

I.  Protein  Metabolism  854 

11.  NucLEiN  OB  Purine  Metabolism  874 

III.  The  History  of  Fat  est  the  Body  884 

IV.  The  Metabolism  of  Carbohydrates  899 


CHAPTER  XII 

THE  BLOOD 

General  Characters  of  the  Blood  915 

I.  The  White  Blood -Corpuscles  918 

II.  The  Red  Blood -Corpuscles  924 

III.  The  Blood-Platelets  944 

IV.  The  Coagulation  of  the  Blood  947 
V.  The  Quantity  and  Composition  of  the  Blood  in  Man  964 


CHAPTER  XIII 

THE  PHYSIOLOGY  OF  THE  CIRCULATION 

I.  General  Features  of  the  Circulation  979 

II.  The  Blood  Pressure  at  Different  Parts  of  the  Vascular 

Circuit  986 

III.  The  Velocity  of  the  Blood  at  Different  Parts  of  the  Vascular 

System  999 

rv.  The  Mechanism  of  the  Heart  Pump  1004 

V.  The  Flow  of  Blood  through  the  Arteries  1034 

VI.  The  Flow  of  Blood  in  the  Veins  1050 

VII.  The  Pulmonary  Circulation  1053 

VIII.  Th^  Causation  of  the  Heart  Beat  1057 

IX.  The  Nervous  Regulation  of  the  Heart  1087 

X.  The  Effect  of  Muscular  Exercise  on  the  Circulation  1099 

XL  The  Nervous  Control  OF  the  Blood-Vessels  1103 

XII.  The  Influence  on  the  Circulation  of  Variations  in  the  Total 

Quantity  OF  Blood  1129 


CONTENTS  xi 

CHAPTER  XIV 

iCTION  PAOE 

LYMPH  AND  TISSUE  FLUIDS  113:5 

CHAPTER  XV 

THE  DEFENCE  OF  THE  ORGANISM  AGAINST  INFECTION 

I.  The  Cellttlar  IVIechanisms  of  Defence  1143 

II.  The  Chemical  Mechanisms  of  Defence  1152 

CHAPTER  XVI 

RESPIRATION 

I.  The  Mechanics  of  the  Respiratory  Mo\t;ments  1162 

n.  The  Chemistry  of  Respiration  1172 

III.  The  Regulation  of  the  Respiratory  Movements  1200 

The  Chemical  Regulation  of  the  Respiratory  Movements     1204 
The  Reflex  Nervous  Regulation  of  Respiration  1214 

IV.  The  Effects  on  Respiration  of  Changes  in  the  Air  Breathed  1225 
V.  The  Mechanisms  of  Oxidation  in  the  Tissues  1233 

CHAPTER  XVn 

RENAL  EXCRETION 

I.  The  Composition  and  Characters  of  the  Urine  1240 

II.  The  Secretion  of  Urine  1264 

III.  The  Physiology  of  Micturition  1289 

CHAPTER  XVni 
THE  SKIN  AND  THE  SKIN  GLANDS  1299 

CHAFJ'ER  XIX 
THE  TEMPERATURE  OF  THE  BODY  AND  ITS  REGULATION     1305 


CHAPTER  XX 
THE  DUCTLESS  GLANDS  131' 


xii  CONTENTS 

BOOK  IV 
REPRODUCTION 

CHAPTER  XXI 
THE  PHYSIOLOGY  OP  REPRODUCTION 

SECTION  PAGE 

I.  The  Essential  Features  of  the  Sexual  Process  1341 

II.  Development  and  Heredity  1356 

III.  Reproduction  in  IVIan  1361 

IV.  Pregnancy  and  Parturition  1376 
V.  The  Secretion  and  Properties  of  Milk  1384 

INDEX  1395 


CHAPTER  I 

INTRODUCTION 

Physiology  in  its  widest  sense  signifies  the  study  of  the  phenomena 
presented  by  living  organisms,  the  classification  of  these  phenomena, 
and  the  recognition  of  their  sequence  and  relative  significance.  Such 
a  range  would  include  many  studies  which  are  not  generally  grouped 
under  the  term  physiology,  and  would  in  fact  correspond  to  the  com- 
prehensive science  of  biology.  Thus  the  study  of  the  relations  of 
living  beings  to  one  another  and  to  their  surroundings  is  the  special 
object  of  the  science  of  oecology.  The  aims  of  physiology  in  its 
restricted  sense  are  the  description,  analysis,  and  classification  of  the 
phenomena  presented  by  the  isolated  organism,  the  allocation  of  every 
function  to  its  appropriate  organ,  and  the  study  of  the  conditions  and 
mechanisuLS  which  determine  each  function. 

The  fundamental  phenomena  of  life  are  essentially  identical 
throughout  the  whole  series  of  living  organisms.  This  continuity  of 
function  is  the  necessary  correlation  of  the  continuity  of  descent, 
which  brings  into  relation  all  members  of  the  animal  and  vegetable 
kingdoms.  No  living  organism  can  therefore  be  regarded  as  outside 
the  sphere  of  our  investigations.  The  interest  of  mankind  in  this 
subject  was,  however,  naturally  awakened  in  connection  with  his  own 
body,  and  the  science,  growing  up  as  ancillary  and  preliminary  to 
medical  studies,  has  always  taken  man  as  its  chief  type  of  study.  In 
the  present  work  the  elucidation  of  the  functions  of  man  will  also  be 
our  first  concern,  and  this  for  two  reasons.  In  the  first  place,  in 
physiology,  as  in  all  other  sciences,  the  motive  of  man's  activity  is  his 
social  instinct  to  increase  the  power  of  his  race  in  the  struggle  for 
existence,  by  the  acquisition  of  control,  either  over  the  external  forces 
of  nature,  which  may  be  turned  to  his  o\vn  benefit,  or  over  the 
factors,  intrinsic  and  extrinsic,  which  tend  to  his  enfeeblement  or  extir- 
pation by  disease  and  death.  Consciously  or  unconsciously,  all  our 
researches  on  physiology,  whether  on  the  higher  animals  or  on  the 
lowest  protozoa,  have  the  welfare  of  man  as  their  ultimate  object.  In 
the  second  place,  the  choice  of  the  higlier  animals  as  our  chief  objects 
of  study  receives  justification  from  the  fact  that  whereas  morpliology, 
or  the  science  of  structure,  must  proceed  from  the  lowest  to  the 
highest  organisation,  the  science  of  function  presents  its  problems  in 

I 


2  PHYSIOLOGY 

their  simplest  form  in  the  most  highly  differentiated  organisms.  In 
the  unicellular  animal  all  the  essential  functions  which  we  associate 
with  living  beings  are  carried  out,  often  simultaneously,  in  one  little 
speck  of  protoplasm.  An  analysis  of  these  functions,  the  determina- 
tion of  their  conditions  and  mechanism,  is  obviously  impossible  under 
such  circumstances.  It  is  only  when,  as  in  the  higher  animals,  one 
part  of  the  living  body  is  differentiated  into  an  organ  which  has  one 
function  and  one  function  only  as  the  outlet  for  its  activities,  that  it 
becomes  possible  to  peer  into  the  details  of  the  function  with  some 
chance  of  discovering  its  ultimate  mechanism. 

Our  especial  preoccupation  with  the  physiology  of  man  will  not 
prevent  our  employment  of  examples  from  any  part  of  the  animal  or 
vegetable  kingdom,  when  light  can  be  thrown  by  their  study  on 
fundamental  physiological  phenomena  common  to  the  whole  of 
the  living  world.  In  many  cases  such  a  study  wiU  enable  us  to 
separate  the  essential  features  in  a  process  from  those  which  have 
been  added  as  auxiliary,  with  increasing  complexity  of  the  structures 
concerned. 

What  are  the  fundamental  phenomena  which  are  wtapt  up  in  our 
conception  of  living  beings  ?  When  dealing  with  the  higher  animals, 
we  are  inclined  to  lay  greater  stress  on  the  phenomena  involving  a 
discharge  of  energy.  Thus  we  should  say  that  a  man  was  alive  if  his 
body  were  warm  and  if  he  were  presenting  spontaneous  movements, 
such  as  those  of  respiration  or  of  the  heart.  The  life  of  a  man  in  the 
ordinary  sense  of  the  term  is  made  up  of  those  movements  which  place 
him  in  relationship  with  his  environment.  For  the  production  of 
these  movements,  as  for  the  maintenance  of  a  constant  body-tempera- 
ture, a  continual  expenditure  of  energy  is  necessary.  Experience 
teaches  us  that  these  movements  come  to  an  end  in  the  absence  of 
food  or  of  oxygen,  and  that  an  increased  call  on  the  energies  of  the 
body  must  always  be  met  by  a  corresponding  increase  in  the  air  and 
in  the  food  supplied.  Two  further  processes  must  therefore  be 
included  among  those  making  up  our  conception  of  life,  viz.  the 
function  of  assimilation  (the  taking  in  and  digestion  of  food),  and  the 
function  of  respiration,  in  which  oxygen  is  absorbed  and  carbon 
dioxide  is  excreted  into  the  surrounding  atmosphere. 

The  substances  which  make  up  our  food-stuffs  are  all  capable  of 
oxidation.  Composed  chiefly  of  carbon  and  hydrogen,  with  some 
oxygen,  nitrogen,  and  sulphur,  they  yield  on  complete  combustion 
carbon  dioxide,  water  and  small  amounts  of  ammonia  or  alhed  bodies, 
and  sulphates.  In  this  process  of  oxidation  there  is  liberation  of  heat. 
In  the  body  a  similar  oxidation  occurs,  the  products  of  oxidation 
being  discharged  into  the  surrounding  medium.  An  amount  of  energy 
is  thus  set  free  which  is  available  for  the  activities  of  the  living  organism. 


INTRODUCTIOX 


Before  we  can  make  any  accurate  investigations  of  the  conditions 
which  determine  these  activities,  We  must  know  whether  the  two  great 
laws  of  chemistry  and  physics,  viz.  the  conservation  of  mass  and  the 
conservation  of  energy,  hold  good  for  the  processes  within  the  living 
body.  The  many  experiments  which  have  been  made  on  this  point 
have  decided  the  question  in  the  affirmative.  Thousands  of  experi- 
ments have  been  made,  both  on  man  and  on  animals,  in  which  the 
total  income  of  the  body,  viz.  food  and  oxygen,  has  been  weighed, 
and  compared  with  the  total  output,  viz.  carbon  dioxide,  water,  and 
bodies  allied  to  ammonia  (urea,  &c.).  In  every  case  complete  equality 
has  been  obtained,  and  we  can  be  certain  that  any  substance  found  in 
the  body  must  have  been  derived  from  without.  There  is  no  creation 
or  destruction  of  matter  in  the  body. 

The  determination  of  the  equation  in  the  case  of  the  total  energy 
of  the  body  is  rather  more  difficult.  We  have,  in  the  first  place,  to 
measure  the  total  income  and  output  of  the  body,  and  to  determine 
the  total  heat  which  would  be  evolved  by  the  oxidation  of  the  food- 
stuffs taken  in  to  the  carbon  dioxide,  water,  &c.,  that  are  given  out. 
We  must  then  compare  the  figure  so  obtained  with  the  actual  outpi  t 
of  energy  by  the  body.  The  latter  can  be  measured  in  terms  of  heat 
by  placing  the  animal  inside  a  calorimeter.  Many  practical  difficulties 
arise  in  the  performance  of  the  experiment,  in  consequence  of  the 
necessity  of  providing  the  animal  with  a  constant  supply  of  air  to 
breathe,  and  of  allowing  for  the  continual  loss  of  water  by  evaporation 
which  is  going  on  at  the  surface  of  the  animal.  The  first  accurate 
experiments  of  this  nature  were  made  by  Rubner.  This  observer 
determined  by  means  of  the  calorimeter  the  total  heat  loss  of  dogs. 
In  the  same  animals  the  material  income  and  output  of  the  body  were 
measured,  and  a  calculation  was  made  as  to  the  amount  of  energy 
which  would  be  set  free  in  the  body  by  the  processes  of  oxidation 
involved  in  the  change  of  material  observed.  The  following  Table 
represents  a  summary  of  Rubner 's  results  : 


!>'.-. 

Condition  of  dog. 

Calriilatcci 

licat 
production. 

Heat  lo>.-  deter- 
mined calori- 
nietrically. 

Imration 

of 

experiment. 

1. 

2. 

Fasting     . 

Ciil. 

259-3 
545-6 

Cal. 

2610 
528-3 

l>ays. 
5 
2 

3. 

4. 
5. 
6. 

Fed  with  meat  . 
Fed  w-ith  fat      . 
Meat  and  fat 

329-9 
3020 
332- 1 
311-6 

333-9 
299-1 
3300 
331-0 

1 

5 

12 

8 

7. 
8. 

Fed  with  meat  . 

3750 
683-0 

379-5 
681-3 

6 

7 

4  PHYSIOLOGY 

It  will  be  seen  that  the  average  difference  between  the  calculated 
and  observed  results  amounts  only  to  101  per  cent. — an  amazing 
agreement  considering  the  extreme  difficulties  of  the  experimental 
methods  involved.  The  important  deduction  to  be  drawn  from  these 
observations  is  that  the  food -stuffs  which  are  oxidised  in  the  body 
develop  in  this  process  exactly  the  same  amount  of  energy  as  when 
they  are  burnt  up  outside  the  body. 

From  one  aspect,  therefore,  the  animal  body  may  be  looked  upon 
as  a  machine  for  the  transformation  of  the  potential  energy  of  the 
food -stuffs  into  kinetic  energy,  represented  by  the  warmth  and  move- 
ments of  the  body  as  well  as  by  other  physical  changes  involved  in 
vital  processes.  In  the  living  organism  we  cannot,  however,  distinguish 
between  the  source  of  energy  and  the  machinery,  as  we  can  in  the  case 
of  our  engines.  When  we  endeavour  to  trace  the  food-stuffs  after  their 
entry  into  the  body,  we  lose  sight  of  them  at  the  point  where  they  are 
built  up  to  form  ajiparently  an  integral  part  of  the  living  framework. 
During  activity  there  is  a  discharge  of  the  products  of  oxidation  of  the 
food-stuffs  from  this  living  matter,  which  therefore  becomes  reduced 
in  mass.  This  reduction,  or  disintegration  of  the  living  matter, 
associated  with  activity,  is  always  followed  by  a  period  of  increased 
integration,  during  which  the  organism  grows  by  the  assimilation  of 
more  food.  Our  conception  of  life  must  therefore  involve  the  idea  of 
a  constantly  recurring  cycle  of  processes,  one  of  building  up,  repair,  or 
integration,  and  the  other,  associated  with  activity,  of  destruction  or 
disintegration.  If  the  former  process  predominates,  we  obtain  a 
steady  increase  in  the  mass  of  the  organism,  an  increase  which  we 
speak  of  as  growth,  and  in  many  cases,  as  in  that  of  plants,  it  is  this 
power  of  growth  which  we  take  as  our  criterion  of  the  existence  of  life. 
In  fact,  the  possession  by  the  green  parts  of  plants  of  the  power  of 
utilising  the  energies  of  the  sun's  rays  for  the  integration  of  food -stuffs, 
such  as  starch,  with  a  high  potential  energy,  is  the  necessary  condition 
for  the  existence  of  all  higher  forms  of  life  on  this  earth. 

Closely  associated  with  the  property  of  growth  is  the  power 
possessed  by  all  living  organisms  of  repair,  i.e.  the  replacement  by 
newly  formed  healthy  living  material  of  parts  which  have  been 
damaged  by  external  events. 

The  process  of  growth  does  not,  in  the  individual,  proceed  indefi- 
nitely. At  a  certain  stage  in  its  life  every  organism  divides,  and  a 
part  or  parts  of  its  substance  are  thrown  off  to  form  new  individuals, 
each  of  them  endowed  with  the  same  properties  as  the  parent  organism, 
and  destined  to  grow  until  they  are  indistinguishable  from  the  organism 
whence  they  were  derived.  In  the  lowest  forms  of  life,  the  unicellular 
organisms,  these  processes  of  growth  and  division  may  go  on  until 
brought  to  an  end  by  some  change  in  the  environment  which  will  not 


INTRODTTTIOX  5 

allow  the  necessary  conditions  of  life,  viz.  assimilation  and  disintegra- 
tion, to  proceed.  In  all  the  higher  forms,  however,  after  the  process 
of  reproduction  has  been  completed,  the  parent  organism  begins  to 
undergo  decay,  and  the  processes  of  assimilation  and  repair  no  longer 
keep  pace  with  those  of  destruction,  however  favourable  the  environ- 
ment, until  finally  death  of  the  organism  takes  place. 

All  these  phenomena,  viz.  assimilation,  respiration,  activity  asso- 
ciated with  the  discharge  of  energy,  growth,  reproduction,  and  death 
itself,  are  bound  up  in  our  conception  of  life.  All  have  one  feature  in 
common,  viz.  they  are  subject  to  the  statement  that  every  living 
organism  is  endowed  with  the  power  of  adaptation.  Adaptation 
may  indeed  receive  the  definition  which  Herbert  Spencer  has  applied 
to  life  — "  the  continuous  adjustment  of  internal  relations  to 
external  relations."  A  living  organism  may  be  regarded  as  a  highly 
unstable  chemical  system  which  tends  to  increase  itself  continuously 
under  the  average  of  the  conditions  to  which  it  is  subject,  but  under- 
goes disintegration  as  a  result  of  any  variation  from  this  average. 
It  is  evident  that  the  sole  condition  for  the  survival  of  the  organism 
is  that  any  such  act  of  disintegration  shall  result  in  so  modifying 
the  relation  of  the  system  to  the  environment  that  it  is  once  more 
restored  to  the  average  in  which  assimilation  can  be  resumed.  Every 
phase  of  activity  in  a  living  being  must  be  not  only  a  necessary  sequence 
of  some  antecedent  change  in  its  environment,  but  must  be  so  adapted 
to  this  change  as  to  tend  to  its  neutrahsation,  and  so  to  the  survival 
of  the  organism.  This  is  what  is  meant  by  '  adaptation.'  Not 
only  does  it  involve  the  teleological  conception  that  every  normal 
activity  must  be  for  the  good  of  the  organism,  but  it  must  also  apply 
to  all  the  relations  of  living  beings.  It  must  therefore  be  the  guiding 
principle,  not  only  in  physiology  with  its  special  preoccupation  with 
the  internal  relations  of  the  parts  of  the  organism,  but  also  in  the  other 
branches  of  biology,  which  treat  of  the  relations  of  the  living  animal 
to  its  environment,  and  of  the  factors  which  determine  its  survival  in 
the  struggle  for  existence.  The  origin  of  new  species  and  the  succession 
of  the  different  forms  of  life  upon  this  earth  depend  on  the  varying 
perfection  of  the  mechanisms  of  adaptation. 

We  may  imagine  that  the  first  step  in  the  evolution  of  life  was  taken 
during  the  chaotic  chemical  interchanges  which  accompanied  the 
cooling  down  of  the  molten  mass  forming  the  earth,  when  some  com- 
pound was  formed,  probably  with  absorption  of  heat,  endowed  with 
the  property  of  continuous  polymerisation  and  growth  at  the  expense 
of  surrounding  material.  Such  a  substance  could  continue  to  exist 
only  at  the  expense  of  the  energy  derived  from  the  surrounding  medium, 
and  would  undergo  destruction  with  any  stormy  change  in  its  environ- 
ment.    Out  of  the  many  such  compounds  which  mifjht  have  come  into 


6  PHYSIOLOGY 

being,  only  such  would  survive  in  which  the  process  of  exothermic 
disintegration  tended  towards  a  condition  of  greater  stability,  so  that 
the  process  might  come  to  an  end,  and  the  organism  or  compound  be 
enabled  to  await  the  more  favourable  conditions  necessary  for  the 
continuance  of  its  growth.     With  the  continued  cooling  of  the  earth, 
the  new  production  of  endothermic  compounds  would  become  rarer 
and  rarer ;  and  in  all  probability  the  beginning  of  life,  as  we  know  it, 
was  the  formation  of  some  complex  substance,  analogous  to  the  present 
chlorophyll  corpuscles,  with  the  power  of  absorbing  the  newly  pene- 
trating sun's  rays  and  utilising  them  for  the  endothermic  formation  of 
further  unstable  compounds.     Once  given  an  unstable  system,  such  as 
we  have    imagined,  the  great  jjrinciple  laid  down  by  Darwin,  viz. 
survival  of  the  fittest,  will  sufE.ce  to  account  for  the  production  from 
it  by  evolution  of  the  ever-increasing  variety  of  living  beings  which 
have  appeared  in  the  later  history  of  this  globe.     The  '  adaptation,' 
i.e.  the  reactions  of  the  primitive  Hving  material  to  changes  in  its 
environment,  must  become  ever  more  and  more  complex,  since  only 
by  means  of  increasing  variety  of  reaction  is  it  possible  to  provide  for 
the  stability  of  the  system  within  greater  and  greater  range  of  external 
conditions.     The  difference  between  higher  and  lower  forms  is  there- 
fore one  of  complexity  of  reaction,  or  of  range  of  adaptation. 
ly'  In  all  the  physiological  processes  which  we  shall  study  in  the  course 
of  this  work,  adaptation  will  be  found  the  constant  and  guiding 
quality.    The  naked  protoplasm  of  the  plasmodium  of  Myxomycetes,  if 
placed  on  a  piece  of  wet  blotting-paper,  will  crawl  towards  an  infusion 
of  dead  leaves,  or  away  from  a  solution  of  quinine.     It  is  the  same 
property  of  adaptation,  the  deciding  factor  in  the  struggle  for  existence, 
which  impels  the  greatest  thinkers  of  our  time  to  spend  long  years  of 
toil  in  the  invention  of  the  means  for  the  offence  and  defence  of  their 
community,  or  for  the  protection  of  mankind  against  disease  and 
death.     The  same  law  which  determines  the  downward  growth  of  the 
root  in  plants  is  responsible  for  the  existence  to-day  of  all  the  sciences 
of  which  mankind  is  proud. 

This  "  adjustment  of  internal  to  external  relations  "  is  possible, 
however,  only  within  strictly  defined  limits,  limits  which  increase  in 
extent  with  rise  in  the  type  of  organism,  and  in  the  complexity  of  its 
powers  of  reaction.  Some  of  these  limiting  conditions  we  shall  have 
to  study  in  the  next  chapter.  Among  the  chief  of  them  are  tempera- 
ture, and  the  presence  of  food  material  and  of  oxygen.  At  the  present 
time  the  limits  of  temperature  may  be  placed  between  0°  and  50°  C. 
Many  organisms,  however,  are  killed  by  the  alteration  of  only  a  few 
degrees  in  the  temperature  of  their  environment.  Every  shifting  of  a 
cold  or  warm  current  in  the  Atlantic,  in  consequence  of  storms  on  the 
surface,  leads  to  the  destruction  of  myriads  of  fish  and  other  denizens 


INTRODUCTION  7 

of  the  sea.  In  the  higher  animals  a  greater  stability  in  face  of  such 
changes  has  been  accomplished  by  the  development  of  a  heat-regulating 
mechanism,  so  that,  provided  sufficient  food  is  available,  the  tempera- 
ture of  the  body  is  maintained  at  a  constant  level,  which  represents 
the  optimum  for  the  discharge  of  the  normal  functions  of  the  consti- 
tuent parts  of  the  body.  The  presence  of  food  material  in  the  environ- 
ment of  the  living  organism  is  a  necessary  condition  for  its  continued 
existence.  In  some  cases,  and  this  we  must  assume  to  be  the  primitive 
condition,  the  food  material  must  be  of  a  given  character  and  form  a 
constant  constituent  of  the  surrounding  medium.  In  the  higher  forms 
however,  the  development  of  the  complex  digestive  system  has  enabled 
the  organism  to  utilise  many  different  kinds  of  food,  while  the  storage 
of  any  excess  of  food  as  reserve  material  in  the  organism,  either  in 
the  form  of  fats  or  carbohydrates,  provides  for  a  constant  supply  of 
food  to  the  constituent  cells  of  the  body,  even  when  it  is  quite  wanting 
in  the  environment.  Since  plants  depend  for  their  food  in  the  first 
place  on  the  carbohydrates  produced  within  the  chlorophyll  corpuscles 
out  of  the  atmospheric  carbon  dioxide  by  the  energy  of  the  sun's  rays, 
necessary  conditions  for  their  existence  will  be  sunlight  and  the  presence 
of  this  gas  in  the  surrounding  atmosphere. 

One  other  necessary  condition  for  the  existence  of  life  is  the  presence 
of  water.  Although  this  substance  cannot  furnish  any  energy  to  the 
complex  molecules  of  which  the  livmg  matter  is  composed,  it  is  an 
essential  constituent  of  all  living  matter,  and  takes  part  in  all  the 
changes  which  determine  the  transformations  of  matter  and  energy  in 
the  organism. 

This  short  summary  of  the  chief  characteristics  of  living  beings 
would  be  incomplete  without  the  mention  of  what  is  perhaps  their 
distinctive  feature,  namely,  organisation.  Although  little  marked  in 
the  lowest  members  of  the  living  kingdom,  where  we  can  detect  only 
a  speck  of  structureless  material  containing  a  few  granules,  of  which 
one  or  more,  in  consequence  of  their  reaction  to  stains,  are  distinguished 
by  the  name  of  a  nucleus,  in  the  higher  members  this  organisation 
becomes  more  and  more  marked.  The  increased  complexity  of 
organisation,  which  we  often  speak  of  as  histological  differentiation, 
runs  parallel  with-  increasing  range  of  power  of  adaptation,  and 
with  increasing  efficiency  of  adaptive  reactions  attained  by  the  setting 
apart  of  special  structures  (organs)  for  the  performance  of  definite 
functions.  This  parallelism  between  the  development  of  function  and 
structure  justifies  us  in  the  assumption  generally,  though  often  only 
tacitly,  accepted  by  physiologists,  that  the  structure  is  the  deter- 
mining factor  for  the  function.  "We  might  regard  the  histological 
differentiation  as  representing  merely  a  continuation  of  the  increasing 
molecular    complexity,    which    we    assumed    must    accompany    and 


8  PHYSIOLOGY 

determine  every  widening  in  the  range  of  the  adaptive  power  of  the 
organism. 

To  sum  up  : — our  objects  in  the  study  of  physiology  inchide  the 
description  of  the  chief  reactions  of  the  body  to  changes  in  itS  environ- 
ment, the  analysis  of  these  reactions  into  the  simpler  reactions  of 
which  they  are  made  up,  and  the  assignment  to  each  differentiated 
structure  of  the  organism  its  part  in  every  reaction.  We  must  deter- 
mine the  conditions  under  which  each  reaction  takes  place,  so  that  we 
may  learn  to  evoke  any  part  of  it  at  will  by  application  of  the 
appropriate  stimulus,  i.e.  by  effective  change  of  environment.  A 
reaction  involves  expenditure  of  energy,  and  this  can  be  derived  only 
from  chemical  change  in  the  reacting  organ,  and  ultimately  from  the 
disintegration  or  oxidation  of  the  food-stuffs. 

Our  next  task  must  be,  therefore,  the  analysis  of  the  energetic  and 
material  changes,  with  a  view  to  determining  the  whole  sequence  of 
events,  from  the  occurrence  of  the  external  exciting  change  to  the 
finished  reaction,  which  will  alter  in  the  direction  of  protection  the 
relation  of  the  organism  to  its  environment.  In  short,  it  is  the  office 
of  physiology  to  discover  the  routine  sequence  of  events  in  the  living 
organism  under  all  manner  of  conditions.  In  attacking  this  problem 
our  methods  cannot  differ  fundamentally  from  those  of  the  physicist 
and  chemist.  In  every  case  our  experiments  will  consist  in  the 
observation  and  measurement  of  movements  of  one  kind  or  another 
which  we  shall,  interpret  in  terms  of  mass  or'^ergy.  Physiology,  if  it 
could  be  completed,  would  therefore  describe  the  how  of  every  process 
in  the  body.  It  would  state  the  sequence  of  events  and  would 
summarise  these  as  so-called  '  laws.'  These  laws  would,  however,  no 
more  explain  the  phenomena  of  life  than  does  the  '  law  of  gravita- 
tion '  explain  the  fact  that  two  masses  tend  to  move  towards  one 
another  wdth  uniform  acceleration.  Nor  can  we  hope  to  explain 
physiological  phenomena  by  reference  to  the  laws  of  physics  and 
chemistry,  since  these  themselves  are  only  expressions  of  sequences, 
and  not  explanations.  With  every  growth  in  science,  however,  its 
generaUsations  become  wider  and  its  laws  summarise  ever  more 
extensive  groups  of  phenomena.  We  have  no  reason  for  asserting 
that,  in  the  course  of  research,  we  may  not  finally  succeed  in  describing 
vital  phenomena  in  the  "  conceptual  shorthand  "  *  used  by  the 
physicist,  involving  his  ideal  world  of  ether,  atom,  and  molecule.  At 
present  we  are  far  from  such  a  consummation.  The  princij)le  of 
adaptation  is  the  only  formula  which  will  include  all  the  phenomena 
of  living  beings,  and  it  is  difficult  to  see  how  this  principle  can  be 
expressed  by  means  of  the  concepts  of  the  physicist. 

This  difficulty,  which  must  be  felt  with  greater  force  the  more 
*  Karl  Pearson,  "Grammar  of  Science,"  p.  328  et  seg.  (2nd  ed.) 


INTRODUCTION  9 

deeply  the  physiologist  endeavours  to  peer  into  the  processes  within 
the  living  cells,  has  led  some,  even  at  the  present  day,  to  the  assump- 
tion of  some  special  quality  in  living  organisms  which  is  designated  as 
'  vital  force  '  or  '  vital  activity/  Such  views  are  classified  together 
under  the  term  vitalism.  From  his  beginning  man  has  been  accustomed 
to  draw  a  sharp  line  of  distinction  between  those  phenomena  which 
by  their  constant  occurrence  seemed  to  him  natural,  and  therefore 
explicable,  and  those  phenomena  of  which  he  could  not  see  the  deter- 
mining antecedent,  and  which  were  to  him,  therefore,  anomic  and 
capricious.  To  the  latter  he  set  up  graven  images,  and  not  perceiving 
his  own  springs  of  action,  endowed  them  with  a  self-determining 
personality  such  as  he  imagined  himself  to  possess.  This  procedure, 
though  possessing  certain  advantages  in  allowing  him  to  perform  his 
common  duties  free  from  the  ever-lurking  fear  of  supernatural  inter- 
ference, suffered  from  the  great  drawback  that  it  fenced  off  unknown 
phenomena  as  unknowable  and  not  to  be  known.  It  has  therefore 
acted  as  a  continual  check  on  the  growth  of  man's  knowledge  and 
control  of  his  environment.  Such  a  graven  image  is  vitalism.  As  a 
working  hypothesis  it  must  be  sterile.  Just  as  the  hypothesis  of  special 
creation  would  impede  all  research  into  the  relationships  of  animals 
and  plants,  so  vitalism  would  stay  the  hand  of  the  physiologist  in  his 
endeavours  to  determine  the  changes  which  occur  within  the  living 
organism.  In  many  cases,  however,  the  terms  '  vitalism  '  and  its 
antithesis  '  mechanism  '  are  used  unjustifiably.  The  production  of 
energy  within  the  body  is  due  to  the  oxidation  of  the  food-stuffs.  In 
certain  functions  it  is  not  yet  fully  established  whether  the  changes 
involved  take  place  at  the  expense  of  the  energy,  hydrostatic  pressure 
or  otherwise,  of  the  fluids  outside  the  cells,  or  whether  energy  is 
supplied  to  the  process  by  the  cells  themselves  at  the  expense  of 
oxidative  changes  occurring  in  their  living  substance.  Both  views  are 
possible,  but  the  adoption  of  either  by  a  physiologist  does  not  justify 
the  statement  that  he  is  a  '  vitalist,'  '  neo-vitalist,'  or  '  mechanist.' 
The  office  of  the  physiologist  is  the  determination  of  the  changes  which 
occur  in  the  living  body  and  the  establishment  of  the  causal  nexus 
{i.e.  the  routine  of  sequences)  between  them.  For  such  a  man  to 
describe  himself  as  a  vitalist  or  mechanist  is  as  germane  to  the  subject 
as  if  he  were  to  call  himself  a  Trinitarian  or  a  Plymouth  Brother. 

Throughout  this  chapter  we  have  assumed  no  necessary  dividing 
line  between  the  different  classes  of  phenomena  in  the  conceptual 
universe,  although  in  the  present  state  of  our  knowledge  we  are  far 
from  being  able  to  include  the  whole  of  them  under  the  same  general 
laws.  It  might  be  objected  that  in  taking  up  this  attitude  we  had 
left  out  of  account  one  supreme  fact,  viz.  the  existence  of  conscious- 
ness in  ourselves.     As  a  comparative  and  objective  study,  however, 


10  PHYSIOLOGY 

physiology  is  concerned,  not  with  the  study  of  consciousness,  but  with 
the  conceptions  in  consciousness  of  the  'phenomena  presented  by  living 
beings.  Consciousness,  in  fact,  we  know  only  in  ourselves.  From  the 
actions  of  other  living  beings  similarly  organised,  we  infer  in  them 
the  existence  of  a  similar  consciousness.  Again,  from  the  fact  that  the 
reactions  of  the  higher  mammals  are  evidently  determined,  not  by 
immediate  impressions,  but  largely  by  stored-up  impressions  of  past 
stimuli,  we  credit  them  also  with  a  certain  but  lower  degree  of  con- 
sciousness. As  we  descend  the  scale  of  animal  hfe,  evidence  of  the 
existence  of  consciousness,  as  we  know  it,  rapidly  diminishes  and 
finally  disappears,  though  it  is  impossible  to  draw  a  sharp  line  between 
those  animals  which  possess  consciousness  and  those  in  which  it  is 
absent.  That  it  is  a  necessary  accompaniment  of  life  is  certainly  not 
the  case.  A  man  is  living  though  he  is  asleep,  anaesthetised,  or  stunned, 
and  it  would  be  absurd  to  speak  of  the  consciousness  of  a  cabbage. 
Consciousness  is,  in  fact,  connected  with  the  possession  of  a  highly 
developed  central  nervous  system,  and  its  activity  is  in  proportion  to 
the  complexity  of  this  system.  Since  the  brain  with  all  the  other 
organs  of  the  body  is  derived  from  a  simple  cell,  the  fertilised  ovum, 
similar  in  its  absence  of  differentiation  to  the  lowest  organisms,  it 
might  be  argued  that  all  types  of  life  are  endowed  with  something 
which  is  not  consciousness,  but  which  has  the  potentiality  of  developing 
into  consciousness.  To  such  a  hypothetical  property  Lloyd  Morgan 
has  given  the  name  '  metakinesis.'  We  have,  however,  no  means  of 
judging  of  the  presence  or  absence  of  this  hypothetical  quality  and 
s'ill  less  of  determining  whether  it  is  a  property  only  of  living  substance, 
or  is  shared  also  by  the  atoms  of  so-called  dead  material.  Moreover, 
since  this  hypothetical  quality  does  not  claim  to  be  a  form  of  energy, 
it  need  not  trouble  us  in  our  study  of  the  energy-changes  in  the  body 
and  the  conditions  which  determine  them. 


BOOK  I 
GENERAL  PHYSIOLOCi^ 


CHAPTER  II 
THE   STRUCTURAL   BASIS   OF  THE   BODY 

THE   CELL 

All  the  higher  animals  and  plants,  when  submitted  to  microscopic 
examination,  are  seen  to  consist  of  structural  units  which  are  spoken  of 
as  cells.  In  each  organ  we  find  a  mass  of  these  cells  closely  resembling 
one  another  in  all  respects,  and  we  may  therefore  regard  the  function 
of  any  organ  as  the  sum  of  the  functions  of  its  constituent  cells.  Indeed, 
any  given  reaction  of  the  whole  body  is  the  resultant  of  the  reactions 
of  the  unlike  cells  of  which  the  body  is  composed.  The  cell  is  therefore 
the  physiological  as  well  as  the  structural  unit,  and  it  is  necessary  to 
commence  our  study  of  the  functions  of  the  animal  body  with  some 
consideration  of  the  functions  and  reactions  which  are  common  to  all 
the  structural  units. 

This  composite  structure  is  peculiar  to  the  higher  forms  of  life. 
Amongst  the  lower  forms,  both  animal  and  vegetable,  an  immense 
number  of  organisms  consist  only  of  a  single  cell.  In  this  cell  are 
represented  all  the  phenomena  of  life,  all  the  adapted  reactions  which 
we  associate  with  the  life  of  the  higher  organisms.  That  the  uni- 
cellular condition  represents  the  more  primitive  stage  from  which 
the  higher  organisms  have  been  evolved  in  the  course  of  ages  is  indi- 
cated by  the  fact  that  every  one  of  these  higher  organisms  in  the 
course  of  its  development  passes  through  a  unicellular  stage,  namely, 
the  fertilised  ovum.  We  may  assume  that  the  series  of  changes 
attending  the  development  of  the  higher  organism  from  the  egg  is  a 
repetition  in  summary  of  the  changes  which  have  determined  the 
evolution  of  the  species  from  the  primitive  unicellular  type,* 

The  general  characteristics  of  the  cell  present  important  simi- 
larities, whether  we  are  considering  a  cell  which  forms  the  whole  of  an 
organism  or  a  cell  which  is  but  an  infinitesimal  part  of  a  highly  developed 
animal. 

The  name  '  cell '  was  first  applied  by  botanists  to  the  structural 
units  found  by  them  in  plant  tissues,  and  involved  therefore  the  idea 
of  certain  qualities  which  do  not  enter  into  our  present  conception  of 
the  term.  A  section  through  the  stem  of  a  growing  plant  shows  it  to 
be  made  up  of  an  aggregation  of  cells  in  the  etymological  sense  of  the 

*  This  assumption  is  often  spoken  of  as  the  'law  of  recapitulation.' 

13 


14 


PHYSIOLOGY 


word,  i.e.  small  sacs  bounded  by  a  wall  of  cellulose  and  containing 
cell  sap.  Immediately  inside  the  cellulose  wall  is  a  thin  layer,  the 
primordial  utricle,  which  encloses  at  one  point  a  spherical  or  oval 
structure  known  as  the  nucleus.  If  the  section  be  taken  from  the 
growing  tip  of  a  plant  (Fig.  1),  the  cell  sap  is  found  to  be  wanting  and 
the  cells  consist  only  of  the  substance  known  as  protoplasm,  which 
later  on  will  form  the  primordial  utricle.     This  with  a  nucleus  is 


Fig.  1.     General  view  of  cells  in  the  growing  root-tip  of  the  onion,  from  a  longitudinal 
section,  enlarged  800  diameters.     (Wilson.) 
a,  non-dividing  cells,  with  chromatin-network  and  deeply  stained  nucleoli  ; 
h,  nuclei  preparing  for  division  (spireme-stage)  ;   c,  dividing  cells  showing  mitotic 
figures  ;   e,  pair  of  daughter-cells  shortly  after  division. 

enclosed  in  a  delicate  cellulose  wall.  The  wall  is  not  an  essential 
constituent,  since  it  is  absent  from  many  vegetable  cells  at  some  period 
of  their  life  and  from  animal  cells  generally. 

A  better  conception  of  the  essentials  of  a  cell  can  be  obtained  by 
the  study  of  a  unicellular  animal  such  as  an  amoeba  (Fig.  2).  This  is 
an  organism  frequenting  stagnant  pools,  of  varying  size  (from  O'l  to 
0'3  mm.  in  diameter),  apparently  of  a  semi-fluid  consistence,  "When 
first  examined  it  is  generally  spherical,  but  in  a  short  time  begins  to 
change  its  form,  putting  out  processes  known  as  pseudopodia.  By 
shifting  the  distribution  of  its  material  among  these  processes,  it  is  able 
to  move  about  and  also  to  ingest  particles  of  food  or  pigment  with 
which  it  may  come  in  contact.  Near  its  centre  a  differentiated  portion 
can  be  distinguished  which  is  known  as  the  Ciucleus.    The  rest  of  the 


THE  .STRUCTURAL  BASIS  OF  THE  BODY 


15 


amoeba,  the  protoplasm  or  cytoplasm,  often  presents  further  differen- 
tiation into  an  outer  clear  layer  and  an  inner  finely  granular  substanr  e. 
The  latter  may  contain  coarser  granules,  some  of  food  material,  others 
apparently  formed  in  situ  by  the  surrounding  protoplasm,  and  often 
small  vacuoles  ('  contractile  vacuoles  ')  which  are  continually  altering 
their  size  and  serve  to  keep  up  a  circulation  of  fluid  in  the  interstices 
of  the  cytoplasm.     In  all  cells,  whether  animal  or  vegetable,  with 


w  V 


-/' 


cv 


^m 


Fig.  2.     Amoeba  p-oleus,  an  animal  consisting  of  a  single  naked  cell,  x  280.     (From 
Sedgwick  and  Wilson's  Biology.) 
n,    the    nucleus ;    wv,    water- vacuoles ;    cv,    contractile    vacuole ;    fv,    food- 
vacuole. 


which  we  are  acquainted,  this  twofold  structure  is  also  found.  So 
that  we  may  define  a  cell  as  a  small  mass  of  protoplasm  containing  a 
nucleus. 

Doubt  has  often  been  expressed  whether  a  nucleus  is  to  be  regarded  as 
essential  to  our  conception  of  a  cell.  In  many  of  the  lowest  forms  of  animals 
and  plants,  such  as  the  Flagellata  among  the  former  and  the  Cj'anophyceje 
and  Bacteria  among  the  latter,  no  distinct  nucleus  can  be  demonstrated.  In 
many  of  these  forms  the  dimensions  of  the  whole  organism  are  too  minute  to 
allow  of  any  definite  statement  being  made  as  to  the  presence  or  absence  of 
nuclear  material.  In  the  larger  of  them,  however,  the  cji;oplasm  of  the  cell 
contains  numerous  scattered  granules  which  stain  with  dyes  in  exactly  the 
same  way  as  do  the  nuclei  of  the  cells  of  higher  animals,  and  these  granules 
po.ssess  the  resistance  to  the  action  of  certain  digestive  fluids  which  is  typical 
of  nuclei.  They  may  therefore  be  taken  as  representing  the  nucleus  in  tlie  higher 
forms.  Even  in  the  latter,  at  certain  stages,  namely,  diu-ing  the  division  of 
the  cell,  the  nucleus  breaks  up  into  discrete  parts,  and  there  is  no  reason  for 
believing  that  such  a  scattered  condition  of  the  nuclear  material  raa,j  not  last 
throughout  the  whole  life  of  the  coll, 


16  PHYSIOLOGY 

We  have  defined  a  cell  as  a  small  mass  of  protoplasm  containing  a 
nucleus.  Since  we  shall  have  to  use  the  term  '  protoplasm  '  on  r^.rof 
occasions  in  the  course  of  this  work,  we  must  have  a  definite  concept 
tion  of  what  we  mean  by  it.  The  term  is  often  used  by  histologists  as 
implying  a  substance  of  certain  definite  chemical  and  staining  characters. 
When  employed  by  physiologists  it  generally  implies  any  material 
which  we  can,  on  a  study  of  its  behaviour  to  changes  in  its  environ- 
ment, regard  as  endowed  with  life.  Huxley  has  defined  it  as  "  the 
physical  basis  of  life."  Though  it  may  be  convenient  to  have  a  word 
such  as  protoplasm  signifying  simply  '  living  material,'  it  is  important 
to  remember  that  there  is  no  such  thing  as  a  single  substance' — ^proto- 
plasm. The  reactions  of  every  cell  as  well  as  its  organisation  are  the 
resultant  of  the  molecular  structure  of  the  matter  of  which  it  is  built 
up.  The  gross  methods  of  the  chemist  show  him  that  the  composition 
of  the  '  protoplasm  '  of  the  muscle  cell  is  entirely  different  from  that 
of  a  leucocyte  or  white  blood  corpuscle.  The  finer  methods  of  the 
physiologist  show  him  that  every  sort  of  cell  in  the  body  has  its  own 
manner  of  life,  its  own  peculiarities  of  reaction  to  uniform  changes  in 
its  surroundings.  No  individual  will  react  in  exactly  the  same  manner 
as  another  individual,  even  of  the  same  species,  and  the  reactions  of 
the  whole  organism  are  but  the  sum  of  the  reactions  of  its  constituent 
cells.  There  is  not  one  protoplasm  therefore,  but  an  infinity  of  proto- 
plasms, and  the  use  of  the  term  can  be  justified  only  if  we  keep  this 
fact  in  mind  and  use  the  word  merely  as  a  convenient  abbreviation 
for  any  material  endowed  with  life.  Even  in  a  single  cell  there  is  more 
than  one  kind  of  protoplasm.  In  its  chemical  characters,  in  its  mode 
of  life,  and  in  its  reactions,  the  nucleus  differs  widely  from  the  cyto- 
plasm. Both  are  necessary  for  the  life  of  the  cell  and  both  must  be 
regarded,  according  to  our  present  ideas,  as  '  living.'  In  the  cytoplasm 
itself  we  find  structures  or  substances  which  we  must  regard  as  on 
their  way  to  protoplasm  or  as  products  of  the  breakdown  of  proto- 
plasm ;  but  in  many  cases  it  is  impossible  to  say  whether  a  given 
material  is  to  be  regarded  as  lifeless  or  as  reactive  living  matter. 
Even  in  a  single  cell  we  may  have  differentiation  among  its  different 
parts,  one  part  serving  for  the  process  of  digestion  while  other  parts 
are  employed  for  the  purpose  of  locomotion.  Here  again  there  must 
be  chemical  differences,  and  therefore  different  protoplasms.  In 
this  work,  therefore,  protoplasm  will  be  used  in  its  broadest  sense, 
namely,  as  the  physical  basis  of  living  organisms. 

STRUCTURE  OF  THE  CELL.  In  every  cell  can  be  distinguished 
the  two  parts — ^nucleus  and  cytoplasm.  The  nucleus  is  generally  an 
oval  or  spherical  body  lying  near  the  centre  of  the  cell  and  bounded 
by  a  definite  contour  or  nuclear  membrane.  In  its  interior  it  contains 
masses  or  filaments  of  a  materia)  knoA\Ti  as  chromatin,  which  are 


THE  STRUCTURAL  BASIS  OF  THE  BODY 


17 


strung,  so  to  speak,  on  a  fine  network  of  material  known  as  linin. 
Besides  the  granules  of  chromatin,  other  masses  are  sometimes 
Ld  which  stain  in  a  different  manner  and  are  called  nucleoli.  The 
material  filling  up  the  meshes  of  the  network  is  the  nuclear  sap  or 
nucleoplasm.  The  cytoplasm,  which  varies  greatly  in  extent  in  different 
cells,  varies  also  in  its  appearance,  being  sometimes  homogeneous, 
sometimes  alveolar,  sometimes  granular  in  structure.     In  it  can  be 

Attraction-sphere  enclosing  two  centrosomes 


Nucleus 


(  Plasmosome 
or  true 
nucleolus 

Chromatin- 

network 

Linin-network 

Karyosome, 
net-knot,  or 
chromatin- 
nucleolus 


Plastids  lying  in  the 
cytoplasm 


Vacuole 


Passive  bodies  (meta- 
plasm  or  paraplasm) 
suspended  in  the  cy- 
toplasmic meshwork 


Fia.  3.  Diagram  of  a  cell.  Its  basis  consists  of  a  meshwork  containing  numerous 
minute  granules  (microsomes)  and  traversing  a  transparent  ground-substance. 
(Wilson.) 


often  distinguished  differentiated  parts  which  may  be  regarded  as 
organs  of  the  cell.  Thus  in  the  amoeba  we  have  the  contractile 
vacuoles  already  mentioned.  In  the  green  parts  of  plants  the  cyto- 
plasm contains  green  granules,  the  chloroplasts,  whose  special  function 
it  is  to  assimilate  carbon  dioxide  from  the  atmosphere,  and  by  means 
of  the  energ)^  of  the  sun's  rays  to  convert  this  into  starch  with  the 
evolution  of  oxygen.  Other  parts  of  the  plant  have  similar  granules, 
the  leucoplasts,  whose  office  it  is  to  build  up  sugar  into  starch,  and  it 
is  possible  that  other  kinds  of  these  '  plastids  '  with  special  chemical 
functions  are  present  in  the  cytoplasm  of  many  cells.  In  addition  to 
these  cell  organs,  the  cytoplasm  may  contain  granules  which  represent 
stages  in  the  metabolism  of  the  cell  and  are  either  food  material  which 
is  being  assimilated  or  produces  of  the  disintegration  of  the  protoplasm, 
formed  either  for  the  service  of  the  cell  itself  or,  in  the  case  of  the  multi- 

2 


18  PHYSIOLOGY 

cellular  animals,  for  the  service  of  the  other  cells  of  the  organism. 
Others  of  these  granules  may  represent  reserve  material,  i.e.  excess 
of  nourishment  which  has  been  put  aside  by  the  cell  in  an  insoluble 
form,  to  serve  for  its  subsequent  needs  in  times  of  scarcity. 

THE  PHYSICAL  STRUCTURE  OF  PROTOPLASM..  Owing  to  the 
close  similarities  which  exist  between  the  fundamental  properties  of 
all  living  organisms,  histologists  have  sought  to  discover  some  corre- 
sponding uniform  morphological  organisation  of  the  physical  basis  of 
these  phenomena,  namely,  protoplasm. 

It  is  often  impossible,  even  under  the  highest  powers  of  the  micro- 
scope, to  make  out  any  structure  whatsoever  in  the  cytoplasm,  which 
is  spoken  of  then  as  hyaline.  In  most  cases  examination  of  a  cell, 
even  unstained,  shows  some  differentiation  between  a  more  or  less 
regular  framework  or  meshwork  and  a  more  fluid  portion  filling  up  its 
interstices,  and  these  appearances  are  still  more  manifest  when  the 
cells  have  been  fixed  by  various  hardening  fluids.  All  the  results 
obtained  in  this  manner  must  be  regarded  with  some  suspicion,  since, 
as  has  been  shown  by  Fischer  and  by  Hardy,  it  is  possible  to  imitate 
artificially  the  various  structures,  which  have  been  assigned  as 
characteristic  of  protoplasm,  by  hardening  a  homogeneous  colloidal 
solution  such  as  egg-white  by  different  methods  and  with  difierent 
agents.  The  theories  of  protoplasmic  structure  can  be  classified  under 
three  heads  : 

1.  The  Granular  Theory  of  Altmann.  By  the  use  of  certain 
hardening  reagents,  a  dense  mass  of  spherical  or  rod-shaped  granules 
may  be  demonstrated  in  almost  all  cells  of  the  body  (Fig.  4).  These 
granules  have  been  regarded  by  Altmann  as  the  elementary  particles 
of  life,  and  he  locates  in  them  the  various  vital  functions,  the  sum  of 
which  make  up  the  life  of  the  cell.  According  to  Altmann  these  gxanules 
can  only  arise  from  the  division  of  pre-existing  granules,  and  he  has 
formulated  the  phrase  omne  granulum  e  yranulo,  which  is  a  further 
extension  of  Virchow's  sentence  omnis  cellula  e  cellula.  It  is  probable 
that  a  number  of  different  kinds  of  structures  of  varying  importance 
are  included  among  Altmann's  granules.  In  some  cases  they  are  the 
products  of  the  activity  of  the  cytoplasm  and,  as  in  secreting  cells, 
will  be  later  on  cast  out  with  water  and  salts  as  the  specific  secretion. 
In  other  cases  they  may  be  cell  organs  or  plastids  with  the  special 
metabolic  functions  assigned  to  all  granules  by  Altmann.  In  many 
cases  no  treatment  whatever  will  display  the  existence  of  granules. 

2.  The  Fibrillar  Theory.  By  the  employment  of  appropriate 
methods  of  hardening,  it  is  easy  in  most  cells  to  demonstrate  a  network 
or  clusters  of  fibrils  which  form,  so  to  speak,  a  denser  part  of  the  cell. 
This  fibrillar  network  has  been  named  the  '  spongioplasm  '  in  contra- 
distinction to  the  structureless  material  filling  its  meshes  known  as 


THE  STRUCTURAL  BA8I8  OF  THE  BODY 


19 


'  hyaloplasm.'  A  network  is,  however,  one  of  the  commonest  pseudo- 
structures  produced  in  the  coagulation  of  an  albuminous  fluid  by 
any  means  whatever,  and  it  is  probable  that  in  most  cases  the 
network  which  is  seen  in  hardened  cells  is  simply  an  artefact.  Some- 
times a  large  portion  of  the  protoplasm  may  take  a  fibrillar  form  which 
can  be  detected  even  in  the  unstained   and   unfixed  cell,  and  there 


Fig.  4.     Section  of  liver  stained  to  show  granules,     (Altmann.) 


is  no  doubt  that,  in  certain  phases  at  any  rate,  the  fibrillar  structure 
of  the  protoplasm  is  really  present. 

3.  The  Alveolar  Theory  op  Butschli.  This  theory  may 
be  looked  upon  as  corresponding  morphologically  to  the  granular 
theory  of  Altmann.  H  we  imagine  a  hyahne  protoplasm  which  is 
continually  manufacturing  metaplasmic  products  and  storing  them 
up  in  its  protoplasm,  these  products  will  be  deposited  as  spherules 
gradually  increasing  in  size,  so  that  the  protoplasm  between  them 
will  be  converted  into  alveolar  partitions  between  the  droplets.  In 
many  an  egg  cell,  where  there  is  a  growth  of  protoplasm  from  this 
building  up  of  food  into  reserve  materials,  the  development  of  such 
an  alveolar  structure  can  be  followed  in  the  living  protoplasm,  and 
such  cells  when  mature  show  a  marked  alveolar  structure  whether 
examined  fresh  or  in  the  hardened  and  stained  condition.  Such  a 
protoplasm  would  be  practically  an  emulsion  of  one  fluid  in  another, 
and  according  to  Butschli  artificial  emulsions,  made  by  mixing  rancid 
oil  with  sodium  carbonate  solutions,  may  show  under  the  microscope 
a  very  close  resemblance  to  cell  protoplasm  (Fig.  6),  and  may  even 
exhibit  amoeboid  changes  of  form  in  consequence  of  the  diffusion 
currents  set  up  at  the  surface  of  the  drop  between  its  contents  and  the 
surrounding  water.    Most  histologists  are  in  accord  that  none  of  the 


20 


PHYSIOLOGY 


Fig.  5.  Diagram  of  a  cell, 
highly  magnified.  (Schafer.) 
p,  protoplasm,  consisting  of 
hyaloplasm  and  a  network  of 
spongioplasm  ;  ex,  exoplasm ; 
end,  endoplasm,  with  distinct 
granules  and  vacuoles; 
c,  double  centrosorae ;  n,  nu- 
cleus; n',  nucleolus. 


above  theories  can  be  regarded  as  applicable  to  all  forms  of  protoplasm, 
but  that  during  the  life  of  a  cell  its  protoplasm,  as  observed  under  the 

microscope,  may  be  either  hyaline  and 
structureless  or  may  present  any  of  the 
structural  modifications  described  above, 
according  to  its  state  of  nutrition  and  the 
form  in  which  its  metabolic  products  are 
laid  dowTi  in  the  cell.  Of  course  it  is 
possible  that,  even  in  the  apparently 
hyaline  protoplasm,  a  structural  differen- 
tiation is  still  present,  but  is  invisible 
owing  to  the  minute  size  of  its  constituent 
parts  or  an  identity  of  refractive  index 
between  the  alveolar  walls  and  their  con- 
tents. The  fact  that  every  chemical  differ- 
entiation occurring  within  the  colloidal  mass 
will  tend  to  cause  differences  of  surface 
tension,  and  therefore  formation  of  droplets,  shows  that  an  alveolar 
structure,  i.e.  one  in  which  there  is  a  large  number  of  surfaces  sepa- 
rating heterogeneous  mixtures 
inside  the  cells,  must  be  of 
very  common  occurrence,  even 
in  cases  where  it  is  not  detect- 
able under  the  microscope. 
Such  a  structure  inust  be 
present,  at  any  rate,  in  those 
cases  where,  apart  from  the 
existence  of  a  solid  cell  wall, 
the  cell  presents  a  certain 
degree  of  rigidity  and  resist- 
ance to  deforming  stress. 

ULTRAMICROSCOPIC  STRUC- 
TURE OF  PROTOPLASM.  Since 
the  study  of  the  behaAaour  of  the 
cell  shows  that  it  must  possess  a 
much  more  complex  structure  or 
organisation  than  that  which  is 
revealed  by  the  microscope,  one, 
that  is  to  saj',  which  permits  of 
the  spatial  differentiation  of  the 
different  chemical  processes  that 
may  occur  at  one  and  the  same 
time  in  the  protoplasm,  many 
theories  have  been  put  forward  of 
an  ultramicroscopic  cell  structure.  Tliough  Spencer  in  1864  spoke  of  physiological 
units  out  of  which  protoplasm  could  be  regarded  as  made  up,  and  Darwin  (1868) 


Fig.  6.  a,  protoplasm  of  an  epidermal  cell  of 
the  crayfish ;  b,  foam-like  appearance 
of  an  emulsion  of  olive  oil.    (Butschli.) 


THE  STRLXTURAL  BASIS  OF  THE  BODY  21 

conceived  ultramicroscopic  particles — gemmules — which  might  be  discharged 
from  every  cell  in  the  body  and,  passing  into  the  reproductive  organs,  serve  as  the 
material  basis  of  heredity,  the  first  elaborate  conception  of  such  a  structure  was 
worked  out  b^  Xageli  (1884).  According  to  Nageli  all  organised  structures  are 
made  up  of  ftiicellae,  minute  particles  arranged  in  definite  order  and  siurounded 
with  water.  ,  For  growth  to  take  place  it  was  necessary  that  the  system  should 
be  in  a  condition  of  '  turgor,'  which  was  determined  by  the  amount  of  water 
between  the  micellae.  These  micellae  arose  in  every  case  from  the  di\ision 
of  pre-existing  micellae,  and  the  vital  properties  of  the  protoplasm  were  to  be 
regarded  as  the  sum  of  the  changes  taking  place  in  the  individual  micellae. 
Similar  conceptions  have  been  put  forward  by  numerous  other  observers, 
each  of  whom  has  applied  a  different  name  to  the  elementary  living  particle, 
such  as  'pangene,'  'plasome,'  'biophor,'  '  biogen-molecule,'  and  many  others. 
The  resemblance  of  these  theories  to  that  of  Altmann  is  ob\-ious,  though 
the  latter  regarded  the  elementary  particle  as  in  many  cases  of  microscopic 
size  and  capable  of  demonstration  by  appropriate  methods  of  staining.  That 
the  cell  possesses  organs  of  smaller  dimensions  than  itself,  which  may  give 
rise  to  like  organs  by  division,  is  shown  by  Schimper's  observations  on  the 
plastids  of  plant  cells.  These  apparently  are  not  formed  by  a  process  of  differen- 
tiation of  the  protoplasm,  but  are  continuous  from  one  generation  to  another 
and  are  reproduced  by  division.  There  is  no  doubt,  however,  that  most  of  the 
granules  to  be  observed  in  the  cytoplasm  are  not  of  this  character,  but  are 
elaborated  by  the  general  cj-toplasm  out  of  the  foodstuffs  which  are  supplied 
to  it ;  and  though  conceptions  such  as  those  of  De  Vries  and  Verworn  are 
often  of  value  as  a  means  of  describing  certain  phenomena  in  the  life  of  the 
cell  and  have  played  a  great  part  in  the  description  of  the  phenomena  of  heredity, 
they  cannot  be  regarded  as  having  any  serious  justification  in  fact.  At  the 
present  time  our  knowledge  of  the  properties  of  the  colloidal  and  capillary 
systems,  which  must  play  so  great  a  part  in  the  organisation  and  reactions  of 
living  protoplasm,  is  much  too  meagre  to  justifj'  weight  being  laid  on  any  theory 
of  the  ultramicroscopic  structmre  of  protoplasm  that  can  at  present  be  put 
forward. 

One  question  which  has  been  much  discussed  relates  to  the  physical 
condition  of  protoplasm.  Is  it  to  be  regarded  as  a  viscous  fluid  or  as  a 
soft  solid  ?  The  perfect  potential  mobility  of  the  protoplasm  of  many 
cells,  as  instanced  by  the  flow  of  a  substance  of  an  amoeba  into  its 
pseudopodia,  or  the  occurrence  of  rapid  streaming  movements  in  the 
threads  of  protoplasm  found  in  many  plants,  e.fj.  the  root  hairs  of 
tradescantia,  indicates  a  fluid  character  for  the  protoplasm.  Against 
such  a  character  has  been  urged  the  fact  that  in  protoplasm  we  may 
have  shape,  organisation,  and  power  of  resistance  to  deformation — 
qualities  which  are  generally  associated  with  the  possession  of  solidity. 
It  must  be  remembered,  however,  that  the  absence  of  resistance  to 
deformation,  which  is  characteristic  of  a  liquid,  applies  only  to  the 
internal  molecules,  and  that  the  surface  of  any  licjuid  is  in  a  condition 
of  tension  which  not  only  limits  deformation,  but  presents  considerable 
resistance  to  any  enlargement  of  the  surface.  Small  water  animals 
take  advantage  of  this  resistance  to  run  freely  oyer  the  surface  of 
water,  although  their  specific  gravity  may  be  greater  than  that  of 


22  PHYSIOLOGY 

water.  The  continued  existence  of  protoplasm  in  a  watery  environ- 
ment shows  that  not  only  must  its  composition  be  different  from  that 
of  its  environment,  but  that  there  must  be  a  distinct  surface  separating 
the  two.  The  superficial  layers  of  the  protoplasm  must  therefore 
be  in  a  condition  of  tension  and  exercise  pressure  on  the  internal 
portions  of  the  cell,  which  will  tend  to  diminish  the  surface  of  the  cell 
to  the  smallest  possible  extent,  i.e.  to  bring  it  into  the  spherical  form. 

This  form  is  characteristic  of  free  cells  in  their  conditions  of  in- 
activity, and  the  smaller  the  mass  of  protoplasm,  supposing  it  to  be 
homogeneous,  the  greater  wnll  be  the  pressure  exerted  by  its  surface 
layer  on  its  contents  and  the  greater  resistance  will  it  present  to 
deformation  of  the  spherical  form.  A  fluid  drop,  if  suspended  in  a  fluid 
with  which  it  is  immiscible,  will  present  greater  rigidity  the  smaller 
its  dimensions.  Almost  any  degree  of  rigidity  can  also  be  imparted  to 
larger  masses  of  fluid  protoplasm  if  their  interior  has  undergone 
chemical  differentiation  so  as  to  be  made  up  of  two  or  more  immiscible 
fluids  arranged  as  droplets  within  alveoli,  as  in  Biitschli's  theory.  In 
such  a  case  every  droplet  will  present  resistance  to  deformation  and 
every  surface  will  resist  penetration  or  extension.  The  resistance  of 
the  surface  in  colloidal  fluids  is  still  further  increased  by  a  property 
common  to  all  these  fluids,  namely,  the  aggregation  in  the  surface  of  a 
greater  concentration  of  the  dissolved  substance  than  is  present  in 
the  underlying  fluid.  If,  for  instance,  we  take  a  beaker  containing  egg- 
white  diluted  100  times,  and  drop  a  steel  magnetised  needle  on  to 
the  surface,  it  will  float  although  it  is  much  heavier  than  the  fluid, 
in  consequence  of  the  resistance  of  the  surface.  If  the  needle  be 
greasy  the  same  thing  will  occur  on  a  glass  of  water.  In  this  case 
the  needle  will  lie  N.  and  S.  On  the  albumen  solution,  however,  the 
needle  will  lie  in  the  position  in  which  it  has  been  dropped.  The 
aggregation  of  the  albumen  molecules  on  the  surface  of  the  fluid  is 
such  that  it  is  practically  solid  and  resists  any  turning  of  the  needle. 
In  consequence  of  the  surface  aggregation  and  solidification  of  the 
colloidal  molecules,  it  is  possible  to  throw  out  the  greater  part  of  the 
albumen  in  a  solid  form  from  a  solution  of  this  substance,  if  it  be  shaken 
up  in  a  bottle  with  a  little  air  so  as  to  make  a  surface.  As  the  fluid 
is  shaken  fresh  surfaces  are  always  being  formed,  and  the  albimien 
aggregating  in  each  of  these  surfaces  has  not  time  to  redissolve  before 
a  fresh  aggregation  occurs  on  a  new  surface,  and  the  films  thus 
produced  gradually  collect  to  form  a  sohd  mass  of  insoluble  protein. 
Protoplasm  may  be  regarded  as  essentially  fluid  in  character,  the  form 
and  rigidity  which  are  acquired  by  most  cells  being  due  to  chemical  and 
physical  differentiation  occurring  in  the  fluid. 

THE  SURFACE  LAYER  OF  CELLS.  Since  it  is  by  means  of  its 
surface  layer  that  the  organism  enters  into  relation  with  its  environ- 


THE  STRUCTURAL  BASIS  OF  THE  BODY  23 

ment,  this  layer  acquires  a  prime  importance  for  the  life  of  the  cell, 
and  we  may  therefore  consider  here  at  greater  length  some  of  the 
properties  of  this  layer,  the  Plastnahaut,  as  it  has  been  called. 

The  superficial  layer  of  the  protoplasm  is  not  to  be  confounded 
with  the  cell  wall.  The  latter,  which  plays  a  great  part  in  the  building 
up  of  vegetable  tis.sues,  is  formed  by  a  process  of  secretion  from  the 
living  protoplasm  and  is  situated  altogether  outside  the  superficial 
Plasmahaut.  The  cell  wall  differs  considerably  in  its  chemical  com- 
position from  the  protoplasm  out  of  which  it  has  been  formed.  In 
most  plants  it  consists  of  cellulose,  a  substance  belonging  to  the 
carbohydrate  group,  and  with  a  composition  represented  by  some 
multiple  of  the  formula  CgHj^Os.  In  other  cells  the  wall  may  be  built 
up  from  calcium  carbonate  or  other  lime  salts,  from  silica,  from  chitin. 
In  many  cases  it  is  perforated  to  allow  the  passage  of  communicating 
strands  of  protoplasm  between  adjacent  cells.  It  is  generally  freely 
permeable  to  all  kinds  of  solutions,  and  in  this  case  plays  no  part  in 
regulating  the  interchanges  of  the  cell  with  the  environment. 

The  superficial  layer  of  protoplasm  represents  that  part  of  the  living 
substance  which  stands  in  immediate  relationship  to  the  environment. 
Every  change  in  the  latter  can  only  influence  the  living  cell  through 
this  layer,  and  it  is  through  this  layer  that  substances  must  pass  on 
their  way  into  the  cell  for  assimilation,  or  out  of  the  cell  for  excre- 
tion. The  retention  of  an  individuality  by  the  cell  must  be  determined 
by  chemical  and  physical  differences  between  this  layer  and  the 
surrounding  fluid.  Since  it  differs  from  the  rest  of  the  protoplasm  in 
the  changes  to  which  it  is  subject,  it  must  also  differ  in  its  chemical 
composition,  apart  altogether  from  the  factors  which,  as  we  saw  above, 
determine  molecular  differences  between  the  surface  and  the  interior 
of  any  colloidal  solution.  On  this  account  one  must  assume  the  exist- 
ence of  a  definite  boundary  layer  of  the  protoplasm,  even  where  it  is 
impossible  to  see  any  differentiation  between  this  layer  and  the  deeper 
parts  under  the  highest  powers  of  the  microscope. 

A  (living)  cell,  which  leads  its  life  in  a  liquid  environment,  must 
take  up  the  greater  part  of  its  food  material  in  the  form  of  solution, 
and  it  is  the  permeability  of  the  superficial  protoplasm  which  will 
determine  the  passage  of  food  substances  from  the  surrounding  medium 
into  the  body  of  the  cell.  The  immiscibility  of  the  protoplasm  with 
the  surrounding  fluid  shows  that  the  permeability  of  the  membrane 
must  be  a  limited  one.  The  qualitative  permeability  can  be  easily 
studied  in  vegetable  cells.  These  present  within  a  cellulose  wall  a 
thin  layer  of  protoplasm  (the  primordial  utricle),  enclosing  a  cell  sap. 
If  the  root  hairs  of  tradescantia  be  immersed  in  a  10  per  cent,  solution 
of  glucose  or  in  a  2  to  3  per  cent,  solution  of  salt,  a  process  of  phsmolysis 
takes  place.     The  cell  sap  diminishes  in  amount  by  the  diffusion  of 


24 


PHYSIOLOGY 


water  outwards  so  that  the  primordial  utricle  shrinks  (Fig.  7).  On 
immersing  the  cells  in  distilled  water,  water  passes  into  the  cell  sap 
until  the  further  expansion  of  the  protoplasmic  layer  is  prevented  by 
the  tension  of  the  surrounding  cell  walls.  This  behaviour  can  be 
explained  only  on  the  assumption  that  the  protoplasm  is  impermeable 
both  to  sugar  and  to  salt,  but  is  freely  permeable  to  molecules  of  water, 
i.e.  it  behaves  as  a  semi-permeable  membrane.  Similar  experiments 
can  be  made  on  animal  cells.  The  most  convenient  for  this  purpose 
are  the  red  blood  corpuscles.  These  also  shrink  when  immersed  in 
salt  solutions  with  a  greater  molecular  concentration  than  would 


12  3  4 

Fig.  7.     Vegetable  cells,  showing  varying  degrees  of  plasmolysis.     (De  Vries.) 

correspond  to  the  plasma  of  the  blood  from  which  the  corpuscles  were 
derived,  whereas  if  placed  in  weak  salt  solutions  or  distilled  water  they 
swell  up  and  burst,  discharging  their  haemoglobin  in  solution  into  the 
surrounding  fluid.  By  comparison  of  various  salts  it  is  found  that 
the  strength  of  each  salt  solution  which  is  just  necessary  to  cause 
plasmolysis  or  haemolysis,  as  the  case  may  be,  is  determined  entirely 
by  its  molecular  concentration,  i.e.  a  decinormal  solution  of  sodium 
chloride  will  be  equivalent  in  its  effects  on  the  cells  to  a  decinormal 
solution  of  potassium  nitrate  or  of  potassium  chloride.  The  imper- 
meability of  the  plasma  skin  does  not  apply  to  all  dissolved  substances. 
Overton  has  found  that,  whereas  this  layer  is  practically  impermeable 
to  salts,  sugars,  and  amino-acids,  it  permits  the  easy  passage  of  mon- 
atomic  alcohols,  aldehydes,  alkaloids,  &c.  All  these  substances  are 
more  soluble  in  ether,  oil,  and  similar  media  than  they  are  in  water. 
The  passage  of  dissolved  substances  through  a  membrane  wetted  by 
the  solvent  depends  on  the  solubility  of  these  substances  in  the  mem- 
brane, and  Overton  therefore  concludes  that  the  superficial  layer  of 
protoplasmic  cells  must  itself  partake  of  a  '  lipoid  '  character,  and  that 
cholesterin  and  lecithin  probably  enter  largely  into  its  composition. 
Thus^only  those  aniline  dyes  which  are  soluble  in  a  mixture  of  melted 
lecithin  and  cholesterin  have  the  property  of  penetrating  the  living 


THE  STRL'CTURAL  BASIS  OF  THE  BODY  25 

cell,  and  only  these  dyes,  such  as  methylene  blue,  neutral  red,  can  be 
used  for  intra  vitam  staining.  For  the  same  reason  substances  which 
have  the  power  of  dissolving  lecithin  and  cholesterin,  such  as  ether  or 
bile  salts,  also  act  as  hsemolytic  agents,  i.e.  they  cause  a  destruction 
of  the  red  blood  cells  by  dissolving  the  superficial  layer  which  is  neces- 
sary for  their  preservation  from  the  solvent  effects  of  the  surrounding 
fluid. 

The  semi-permeability  of  the  plasma  skin  can  be  altered  by  changes 
in  the  saline  concentration  or  other  factors  of  the  surrounding  medium. 
Overton  has  shown  that,  whereas  a  7  per  cent,  solution  of  saccharose 
produces  plasmolysis  in  living  cells,  no  plasmolysis  is  observed  if  they 
are  treated  with  a  solution  containing  3  per  cent,  methyl  alcohol 
flus  7  per  cent,  cane  sugar.  The  superficial  layer,  therefore,  is  able 
to  dissolve  a  mixture  of  methyl  alcohol  and  cane  sugar,  although  it 
has  no  solvent  power  on  cane  sugar  in  pure  watery  solutions.  It  is 
possible  that,  in  order  to  serve  the  nutrient  needs  of  the  cells,  more 
extensive  changes  may  take  place  in  the  permeability  of  the  surface 
layer  under  limited  conditions  of  time  and  space.  There  is  no  doubt, 
for  instance,  that  dextrose,  to  which  the  surface  layer  is  apparentlv 
impermeable,  can  yet  serve  as  a  very  efficient  food  for  the  cell,  and 
one  might  ascribe  the  fact  that  the  cell  assimilates  only  the  food  which 
it  requires  and  no  more,  to  such  limited  changes  in  permeability.  An 
important  factor  in  the  process  of  assimilation,  at  any  rate  by  lowlv 
organised  cells,  must  be  the  relative  solubihty  of  the  absorbed  sub- 
stances in  the  cell  and  its  surrounding  medium  respectively.  When  a 
watery  solution  of  iodine  is  shaken  up  with  chloroform,  the  latter 
sinks  to  the  bottom,  carrying  with  it  the  greater  part  of  the  iodine. 
If  a  watery  solution  of  organic  acid  be  shaken  with  ether,  the  latter 
fluid  will  extract  the  greater  quantity  of  the  acid.  In  no  case  will  the 
extraction  be  complete,  but  there  will  be  a  definite  ratio  between  the 
amount  dissolved  by  the  ether  and  the  amount  dissolved  by  the  water, 
the  so-called  '  coefficient  of  partage,'  depending  on  the  variable 
solubilities  of  the  dissolved  substance  in  the  two  menstrua.  In  the 
same  way  a  mass  of  protoplasm  will  tend  to  absorb  from  the  sur- 
rounding medium  and  to  concentrate  in  itself  all  those  substances 
which  are  more  soluble  in  the  colloidal  system  of  the  protoplasm  than 
in  the  surrounding  fluid,  and  this  process  of  absorption  mav  be  carried 
to  a  very  large  extent,  if  the  dissolved  substances  meet  in  the  cell 
with  any  products  of  protoplasmic  activity  with  which  they  form 
insoluble  compounds  so  that  they  are  removed  from  the  sphere  of 
action.  It  is  probably  by  such  a  process  as  this  that  we  may  account 
for  the  accumulation  of  calcium  or  silicon  in  such  large  quantities  in 
connection  with  the  bodies  of  various  minute  oru^anisms. 

Whereas  assimilation  bv  a  livinjz  cell  is  ultimatelv  conditioned  bv 


26  PHYSIOLOGY 

the  permeability  of  the  surface  protoplasm,  its  form  is  determined  by 
the  tension  of  this  layer.  If  the  tension  is  uniform  at  all  parts  of  the 
surface  the  form  of  the  cell  will  be  spherical.  Any  diminution  of  the 
surface  tension  at  one  point  must  tend  to  cause  a  bulging  of  the  fluid 
contents  at  this  point,  just  as  on  distending  a  rubber  tube  with  one 
weak  spot  in  its  wall  this  suddenly  gives  way  with  the  production  of 
a  large  balloon,  which  rapidly  extends  in  size  and  ruptures  unless  the 
pressure  be  diminished.  Diminution  of  the  surface  tension  at  one  point 
of  the  cell  will  be  attended  by  a  contraction  of  all  the  rest  of  the  surface 
and  a  driving  out  of  the  contents  through  the  weak  part.  This  process 
will  not  as  a  rule  result  in  destruction  of  the  cell ;  the  resulting  pro- 
trusion will  be  limited  by  the  distortion  of  the  internal  alveolar  structure 
of  the  protoplasm  caused  by  any  alteration  of  the  spherical  form  of 
the  cell.  Change  of  form  in  living  structures  thus  depends  ultimately 
on  alterations  in  surface  tension,  return  to  normal  being  effected  by 
the  elastic  reaction  of  the  structural  arrangement  of  the  protoplasm. 
This  point  we  shall  have  to  consider  more  fully  when  dealing  with 
muscular  contraction.  At  present  it  is  sufficient  to  see  how  any  slight 
alteration  in  the  chemical  environment,  such  as  might  be  due  to  the 
presence  of  a  particle  of  food-stuff,  may  cause  local  variations  in  the 
surface  tension  of  the  plasma  skin  and  thus  result  in  the  protrusion  of 
pseudopodia  and  the  ingestion  of  the  food  particle. 

VITAL  PHENOMENA  OF  CELLS.  A.  Assimilation.  The  activity 
of  every  living  beings  whether  uni-  or  multicellular,  can  be  regarded 
as  compounded  of  two  phases,  assimilation  and  dissimilation.  By 
assimilation  we  mean  the  building  up  of  the  living  substance  at  the 
expense  of  material  obtained  from  the  external  world.  In  this  process 
substances  are  formed  of  high  potential  energy,  and  this  energy  can 
be  obtained  only  at  the  expense  either  of  energy  imparted  to  the 
system  at  the  moment  of  assimilation,  as,  e.g.  in  the  assimilation  of 
carbon  from  carbon  dioxide  under  the  influence  of  the  sun's  rays,  or 
of  energy  contained  in  the  food-stuffs  themselves.  In  all  living  orga- 
nisms, except  those  provided  with  chlorophyll  corpuscles,  it  is  the 
latter  method  which  is  adopted,  and  a  food-stuff  therefore  connotes 
some  substance  which  can  be  taken  in  by  the  cell  and  can  serve  to  it 
as  a  source  of  chemical  energy.  The  evolution  of  energy,  which  ia 
required  for  the  movements  and  other  vital  activities  of  the  cell,  is 
derived  from  a  disintegration  or  dissimilation  of  the  protoplasm  and 
is  generally  associated  with  the  process  of  oxidation.  In  assimilation, 
besides  the  building  up  of  living  protoplasm,  there  may  also  be  a 
synthesis  of  more  complex  from  less  complex  compounds,  without 
their  necessary  entry  into  the  structure  of  the  living  molecule.  In  the 
absence  of  any  definite  criteria  by  which  we  may  judge  as  to  the  living 
or  non-living  condition  of  parts  of  the  cell,  it  is  a  little  dangerous  to 


THE  STRUCTURAL  BASIS  OF  THE  BODY  27 

draw  any  hard-and-fast  distinction  between  these  two  sets  of  processes. 
Assimilation  requires  the  ingestion  of  food  into  the  organism,  and  in 
the  second  place  its  digestion,  i.e.  its  solution  in  the  juices  of  the  cells. 
These  two  processes  are  succeeded,  through  stages  which  we  cannot 
trace,  by  an  actual  growth  in  the  living  material.  In  naked  cells 
ingestion  may  occur  either  at  any  part  of  the  surface,  as  in  the  amoeba, 
or  at  a  specialised  portion,  so-called  '  mouth,'  as  in  many  of  the 
infusoria.  Digestion  is  apparently  effected  in  most  cases  by  the  produc- 
tion and  secretion  around  the  ingested  food  particle  of  solutions  con- 
taining ferments,  i.e.  agents  which  have  the  power  of  hydrolysing  the 
different  food-stulis  and  rendering  them  soluble. 

In  the  vast  majority  of  living  organisms  the  energy  for  their 
activities  is  derived  from  the  oxidation,  ultimately  of  the  food-stuffs, 
but  immediately  of  molecules  attached  to  the  living  protoplasm.  A 
necessary  condition,  therefore,  for  the  life  of  these  cells  is  the  presence 
of  oxygen  in  the  surrounding  medium,  from  which  it  is  taken  up  in 
the  molecular  form.  We  may  therefore  speak  of  an  assimilation  of 
oxygen  ;  but  it  is  still  a  matter  of  dispute  whether  the  oxygen  is  built 
up  as  such  in  the  living  molecule  (so-called  intramolecular  oxygen) 
to  be  utilised  for  the  formation  of  carbon  dioxide  when  a  discharge 
of  energy  is  necessary,  or  whether  it  is  only  taken  in  at  the  moment 
when  the  combustion  of  the  carbon  and  hydrogen  constituents  of  the 
food  or  protoplasm  is  necessary  for  the  supply  of  energy.  However 
this  may  be,  products  are  formed  as  a  result  of  this  oxidation  which 
are  of  no  further  value  to  the  cell  and  are  therefore  excreted,  i.e. 
turned  out  of  the  cell.  The  chief  of  these  are  the  jjroducts  of  oxidation 
of  carbon  and  hydrogen,  namely,  carbon  dioxide  and  water.  There 
are  also  many  substances  resulting  from  the  oxidation  of  the  nitro- 
genous portions  of  the  protoplasm,  which  have  to  be  excreted  in  the 
solid  or  dissolved  form. 

Although  the  assimilation  of  oxygen  is  so  general  a  quality  of  li\-ing  proto- 
[jlasiii,  the  presence  of  tliis  gas,  at  any  rate  in  the  free  form,  does  not  seem  to 
be  necessary  for  all  kinds  of  life.  Thus  a  number  of  the  bacteria  arc  known 
which  are  anaerobic,  i.e.  exist  only  in  the  absence  of  oxygen.  Examples  of 
such  are  b.  tetanus,  and  the  bacillus  of  malignant  redema.  In  order  to  cidtivate 
cm. it  is  necessary  to  displace  all  the  air  in  the  cultivating  vessels  by  means 
JV  cufrent  of  hydrogen.  It  has  been  supposed  that  the  ultimate  source  of 
le  energy  of  these  organisms  is  also  derived  from  a  process  of  oxidation,  and 
that  they  differ  from  other  organisms  in  being  able  to  utilise  for  this  purpose 
oxygen  which  is  built  up  into  the  striicture  of  their  food  substances.  It  is 
possil)]e,  however,  that  these  organisms  derive  the  energy  for  the  building 
up  of  their  protoplasm,  for  their  movements,  iltc,  not  from  a  process  of  oxidation 
at  all,  but  from  processes  of  disintegration  of  the  substances  which  they  utilise 
as  food.  It  is  by  such  means  that  in  all  probability  the  intestinal  worms,  fairly 
highly  organised  animals,  are  able  to  exist  in  the  intestine  in  a  mi>diuni  con- 
taining no  oxygen,  but  rich  in  carbon  dioxide.  Here  they  are  plentifully  supplied 
with  foodstuffs  and  can  afford  to  adopt  a  wasteful  method  of  nutrition,  in  which 


28  PHYSIOLOGY 

only  a  small  fraction  of  the  energy  is  obtained  wliich  woiUd  be  produced  by  a 
total  oxidation  of  the  food, 

B.  The  Phenomena  of  Dissimilation.  The  activities  of  a  living  cell 
or  organism  can  be  regarded  in  every  case  as  dependent  originally  on 
environmental  change,  and  are  adapted  to  this  change,  i.e.  are  of 
such  a  nature  that  they  tend  to  preserve  the  organism  intact,  to  favour 
its  growth,  or  prevent  its  destruction.  The  property  of  reacting  in 
such  a  manner  to  changes  in  the  environment  is  fundamental  to  all 
protoplasm  and  is  spoken  of  as  excitability,  and  the  change  which  will 
influence  an  organism  and  cause  a  corresponding  adaptive  change  in 
it  is  known  as  a  stimulus.  Stimuli  may  be  of  various  kinds.  Thus 
mechanical,  thermal,  chemical,  electrical  changes,  light,  and  so  on, 
may  act  as  stimuli.  The  reactions  which  they  evoke  involve  in  every 
case  chemical  changes  in  the  protoplasm,  i.e.  changes  in  the  metabolism 
of  the  cell.  Sometimes  this  change  may  be  assimilatory  in  character, 
leading  to  an  increased  growth  of  the  protoplasm,  or  at  any  rate  to  a 
cessation  of  dissimilation.  In  such  a  case  the  stimulus  is  spoken  of  as 
inhibitory,  because  it  diminishes  or  prevents  the  output  of  energy  by 
the  organism.  The  frequent  result  of  a  stimulus  is  an  increased  output 
of  energy,  which  may  appear  in  the  form  of  movement,  in  the  form  of 
heat,  or  as  chemical  change. 

A  common  feature  of  all  dissimilatory  changes  evoked  by  the  appli- 
cation of  a  stimulus  is  that  the  energy  of  the  reaction  is  always  many 
times  greater  than  the  energy  represented  by  the  stimulus,  the  excess, 
of  course,  being  supplied  at  the  expense  of  the  potential  energy  of  the 
food  material  which  has  been  stored  up  in  or  built  up  into  the  living 
protoplasm.  This  disproportion  between  stimulus  and  reaction  can 
be  well  illustrated  on  an  excitatory  tissue  such  as  muscle.  Thus  in 
one  experiment  the  gastrocnemius  muscle  of  a  frog  was  loaded  with  a 
weight  of  48  gms.  The  nerve  running  to  the  muscle  was  placed  on  a 
hard  surface  and  a  weight  of  half  a  gTamme  was  allowed  to  fall  upon 
it  from  a  height  of  10  mm.  The  muscle  contracted  in  response  to  this 
mechanical  stimulus  applied  to  the  nerve  and  raised  the  weight  3-8  mm. 
In  this  case  the  work  performed  by  the  muscle  was  48  x  3'8  =  182-4 
grm.  mm.,  while  the  potential  energy  of  the  stimulus  represented ^nl^ 
0'5  X  10*0  =  5*0  grm.  mm.  Thus  the  work  performs 
was  thirty-six  times  larger  than  the  energy  of  the  stimulus  applied 
to  the  nerve. 

In  the  case  of  unicellular  organisms,  definite  classes  of  motor 
reaction  to  stimulus  have  been  described.  The  ordinary  retraction  of 
a  unicellular  organism,  such  as  the  vorticella,  in  response  to  a  touch 
is  called  thigmotaxis .  Certain  cells  are  influenced  by  gravity,  tending  to 
rise  or  fall  in  the  surrounding  medium  according  to  the  conditions 
which  favour  their  existence.     A  similar  sensitiveness  to  gravity  is 


THE  STRUCTURAL  BASIS  OF  THE  BODY  29 

observed  in  the  growing  parts  ofj  plants,  where  the  root  always 
grows  downwards  and  the  stem  upwards.  This  reaction  to 
gravity  is  known  "as  geotaxis,  which  is  distinguished  as  '  negative  ' 
or  '  positive  ',  respectively,  according  as  the  plant  grows  in  oppo- 
sition or  in  obedience  to  the  gravitational  attraction.  If  growing  plants 
be  placed  on  the  rim  of  a  wheel  and  rotated  so  that  the  centrifugal 
force  is  greater  than  that  of  gravity,  the  stems  all  grow  towards  the 
centre  of  the  Avheel  while  the  rootlets  grow  outwards.  In  the  same  way 
the  reaction  of  micro-organisms  to  light  is  known  as  phototaxis,  some 
organisms  seeking  the  light  while  others  shun  it.  Among  the  primitive 
reactions  of  cells  perhaps  the  most  important  in  the  life  of  higher 
animals  are  those  grouped  under  the  term  chemiotaxis .  The  fertilisa- 
tion of  the  ovum  in  the  prothallus  of  ferns  is  effected  by  the  penetration 
of  the  antherozoids  produced  in  the  male  organs  at  some  little  distance 
from  the  female  organs.  It  was  shown  by  Pfeffer  that  the  movement  of 
the  antherozoids  towards  the  ova  is  effected  in  response  to  a  chemical 
stimulus,  probably  malic  acid,  since  he  found  that  antherozoids  sus- 
pended in  a  fluid  will  always  swim  towards  any  locality  where  there  is 
a  greater  concentration  of  this  acid.  In  the  same  way  aerobic  bacteria 
are  attracted  by  the  presence  of  oxygen.  If  such  bacteria  are  present 
in  a  solution  with  an  alga,  on  exposure  of  the  fluid  to  light  there  is  an 
evolution  of  oxygen  b}^  the  green  alga,  and  a  consequent  congi-egation 
of  the  bacteria  round  the  seat  of  production  of  the  oxygen.  The 
movements  of  the  white  corpuscles  of  the  blood  of  the  higher  animals 
are  also  largely  determined  by  their  chemical  sensibility,  and  various 
substances  can  be  divided  into  (a)  those  which  exercise  positive  and 
(6)  those  which  exercise  negative  chemiotactic  influence  on  the  leuco- 
cytes. Thus  the  introduction  under  the  skin  of  an  animal  of  a  capillary 
tube  containing  a  solution  of  substances  of  the  first  class,  such  as 
peptone,  tissue  extracts,  or  the  chemical  products  of  certain  bacteria, 
leads  to  an  accumulation  within  the  tube  of  leucocytes  which  pass  to  it 
from  all  the  surrounding  tissues.  Other  substances,  such  as  quinine, 
exert  a  negative  chemiotaxis.  Tubes  filled  with  these,  after  introduc- 
tion into  the  subcutaneous  tissue  of  a  mammal,  will  be  found  many 
hours  later  to  contain  no  leucocytes  at  all. 

~  )NS  OF  THE  NUCLEUS  TO  THE  CYTOPLASM.  The 
I'sal  existence  in  living  cells  of  a  differentiated  nucleus  indicates 
that  the  life  cycle  of  assimilation  and  dissimilation  must  depend  on  an 
interaction  between  the  nucleus  and  cytoplasm,  and  that  each  plays  a 
distinct  part  in  the  sum  of  the  changes  which  make  up  the  life  of  the 
cell.  The  different  staining  reactions  of  nucleus  and  cytoplasm  suggest 
a  corresponding  difference  in  their  chemical  cojuposition,  a  suggestion 
which  is  confirmed  by  analysis.  In  the  building  up  of  protoplasm 
proteins  play  an  important  part.    They  are  not  present,  however,  aa 


30 


PHYSIOLOGY 


simple  proteins,  but  built  up  with  other  complex  bodies  to  form  con- 
jugated proteins.  Whereas  in  the  cytoplasm  these  conjugated  proteins 
consist  chiefly  of  compounds  of  protein  and  lecithin,  in  the  nucleus 
the  chief  constituents  belong  to  the  class  of  nucleo-proteins.  The 
nucleo -proteins  are  of  varying  composition,  and    are    distinguished 


:|v 


A 


CSI^: 


li'^ . 


1 


M 


w 


I       D 


Fig.  8.     Nucleated  and  non-nucleated  fragments  of  Amoeba.     (AViLSON  after  Hofer.) 
A,  B.  An  Amoeba  divided  into  nucleated  and  non-nucleated  halves,  five  minutes 
after  the  operation.     C,  D.  The  two  halves  after  eight  days,  each  containing  a 
contractile  vacuole. 


chiefly  by  the  large  amount  of  phosphorus  in  their  molecule.  A  nucleo- 
protein  can  be  broken  down  into  nuclein  and  protein.  Nuclein 
be  broken  down  into  nucleic  acid  and  a  protein-like  substance,  pro 
mine.  Nuclei  differ  among  each  other  and  at  different  periods  of  their 
existence  or  in  different  conditions  of  activity  according  to  the  greater 
or  less  amount  of  protein  which  is  combined  with  the  nuclein.  The 
latter  seems  to  be  the  essential  constituent  of  cell  nuclei  and  to  be 
present  in  only  small  quantities  in  the  cytoplasm.  The  properties 
and  reactions  of  these  bodies  will  be  dealt  with  at  greater  length  in  the 
next  chapter. 


THE  STRUCTURAL  BASIS  OF  THE  BODY 


31 


In  order  to  appreciate  the  part  played  by  the  nucleus  in  the  ordinary 
cell  processes,  we  must  study  the  behaviour  of  cells  or  parts  of  cells 
deprived  of  a  nucleus  and  compare  it  with  that  of  similar  cells  or 
parts  of  cells  still  containing  a  nucleus.  By  means  of  a  fine  needle  it  is 
possible  to  divide  the  larger  protozoa  into  two  pieces,  one  with  and 
one  witliout  a  imclous.     Hofer.  experimenting  on  the  amoeba,  found 


Fig.  9. 


Regeneration  in  the  \inicellular  animal  Stentor.     (From  Gruber  after 

B.VLBIANI.) 


A.  Animal  divided  into  three  pieces,  each  containing  a  fragment  of  the  nucleus. 
B.  The  three  fragments  shortly  afterwards.  C.  The  three  fragments  after  twenty- 
four  hours,  each  regenerated  to  a  perfect  animal. 

that  the  fragment  containing  the  nucleus  quickly  regenerated  the 
missing  part  and  pursued  a  normal  existence.  On  the  other  hand,  the 
non-nucleated  fragments  showed  no  signs  of  regeneration.  They  might, 
J.  indeed,  live  as  long  as  fourteen  days  after  the  operation  (Fig.  8).  Their 
movements  continued  for  a  short  time  and  then  ceased,  though  the 
pulsations  of  the  contractile  vesicle  were  but  little  affected.  The  power 
of  digestion  of  food  was  completely  lost.  Other  observers  have  shown 
that  Stentor,  an  infusorium  which  possesses  a  fragmented  nucleus, 
may  be  broken  up  into  fragments  of  all  sizes.  Nucleated  fragments  as 
small  as  one-twenty-seventh  the  volume  of  the  entire  animal  are  still 
capable  of  regeneration.  The  wound  quickly  heals  and  the  special 
organs — the  mouth,   with  its  surrounding  cilia,  and  the  contractile 


32 


PHYSIOLOGY 


vacuole — are  regenerated,  but  all  non- nucleated  fragments  quickly 
perish  (Fig.  9). 

Many  similar  observations  have  shown  that  the  non-nucleated 
cytoplasm,  though  it  may  survive  for  some  time  and  perform  normal 
movements  in  response  to  stimuli,  such  as  those  of  ingestion  of  foO(\ 

\\ J 


■M, 


A 


C 


D 


Fit;.  10.  Formation  of  lucinbiancs  by  protoplasmic  fragments  of  plasmolysed  cells. 
(Wilson  after  TowNSEND.) 
A.  Plasmolysed  cell,  leaf-hair  of  Cucurhila,  showing  protoplasmic  balls 
connected  by  strands.  B.  Calyx-hair  of  Gaillardia ;  nucleated  fragment 
with  membrane,  non-nucleated  one  naked.  C.  Root-hair  of  Marchantia  ;  all 
the  fragments,  connected  by  protoplasmic  strands,  have  formed  membranes. 
D.  Leaf-hair  of  Cucurbita  ;  non-nucleated  fragment,  with  membrane,  connected 
with  nucleated  fragment  of  adjoining  cell. 


particles,  loses  entirely  the  power  of  digestion,  secretion,  and  growth. 
In  animals  possessing  a  shell,  a  small  secretion  of  the  lime  salts  may 
occur  on  the  surface,  but  this  process  rapidly  comes  to  an  end  as  the 
store  of  material  in  the  cytoplasm  is  exhausted.  In  vegetable  cells 
it  is  possible  to  break  up  the  protoplasm  by  means  of  plasmolysis 
into  nucleated  and  non-nucleated  parts.  The  nucleated  part  quickly 
forms  a  new  cell  wall.  The  non-nucleated  part  is  unable  to  effect  this 
formation,  and  soon  dies  unless  it  is  in  connection  with  an  adjacent 


THE  STRUCTURAL  BASIS  OF  THE  BODY 


33 


cell  containing  a  nucleus  by  means  of  fine  threads  of  protoplasm 
which  pass  through  pores  in  the  intercellular  septa  (Fig.  10).  In  the 
higher  animals  we  have,  in  the  case  of  the  nerve-cell,  an  example  of 
the  necessity  of  the  nucleus  for  growth.  Here  division  of  the  nerve 
fibre  causes  degeneration  of  the  whole  fibre  separated  from  the  cell 
containing  the  nucleus,  and  regeneration  of  the  fibre,  when  it  occurs, 
is  effected  by  a  down-growth  of  that  part  of  the  fibre  which  is  still  in 
connection  with  the  nucleus.  All  these  facts  show  that  the  power  of 
morphological  as  well  as  of  chemical  synthesis  depends  on  the  presence 
of  a  nucleus.  On  this  account  the  nucleus,  as  we  shall  learn  later  on, 
must  be  regarded  as  the  especial  organ  of  inheritance.  The  trans- 
mission of  the  paternal  qualities  from  one  generation  to  the  next  is 
effected  by  the  entrance  simply  of  the  nuclear  material  of  the  male  cell, 
the  spermatozoon,  into  the  ovum.  In  the  words  of  Claude  Bernard, 
"  the  functional  phenomena  in  which  there  is  expenditure  of  energy 
have  their  seat  in  the  jjrotoplasm  of  the  cell  {i.e.  the  cytoplasm).  The 
nucleus  is  an  apparatus  for  organic  synthesis,  an  instrument  of  produc- 
tion, the  germ  of  the  cell." 

Similar  conclusions  may  be  drawn  from  a  study  of  the  changes  in 
the  nucleus  which  accompany  different  phases  in  the  activity  of  the 
whole   cell.      Thus   in  growing   plant 
cells  the  nucleus  is  always  situated  at 
the  point  of  most  rapid  growth.     In 
the  formation  of  epidermal  cells  the 
nucleus  moves  towards  the  outer  wall 
and  remains  closely  applied  to  it  so 
long  as    it    is    growing   in   thickness. 
When    this    growth    is    finished    the 
nucleus  moves  to  another  part  of  the 
cell.     In  the  formation  of  root   hairs 
the  outgrowth  always  takes  place  in 
the  immediate  neighbourhood  of  the 
nucleus,  which  is  carried  forward  and  remains  near  the   tip   of   the 
growing  hair.     The  active  growth  of  cytoplasm,  which  accompanies 
the  activity  of  secreting  cells,  is  always  associated  with  changes  m  the 
position  and  in  the  size  of  the  nucleus.     Wliere  the  nutritive  activity 
of  the  cell  is  very  intense,  as  in  the  silk  glands  of  various  lepidopterous 
larvae,  the  nucleus  is  found  to  be  very  large  and  much  branched  (Fig.  1 1 ) 
so  as  to  present  the  greatest  possible  extent  of  surface  through  which 
interchanges  can  go  on  between  nucleus  and  cytoplasm. 

The  important  changes  which  the  nucleus  undergoes  in  the  process 
of  cell  division  we  shall  have  to  consider  more  fully  in  the  later  chaptei-s 
of  this  work.  In  the  function  of  assimilation  it  is  natural  to  assume 
that  it  is  those  constituents  of  the  nucleus  which  are  peculiar  to  it 


^^^^^^^iiSS 


Fig.  11.  Branched  nucleus  from 
the  spinning  gland  of  butterfly 
larva  {Pieris).    (Kor.schelt.) 


34 


PHYSIOLOGY 


both  morphologically  and  chemically,  namely,  the  chromatin  filaments, 
which  are  most  directly  concerned.  This  assumption  receives  support 
from  the  changes  which  have  been  observed  to  occur  in  these  filaments 
during  various  phases  of  nutritive  activity  of  the  cell.  The  staining 
powers  of  chromatin  are  in  direct  proportion  to  the  amount  of  nuclein 
it  contains.  In  the  eggs  of  the  shark  it  has  been  shown  that  the  chromo- 
somes undergo  characteristic  changes  during  the  entire  growing  period 


Fig.  12.     Chromosomes  of  the  germinal  vesicle  in  the  shark  Pristiurus,  at  different 
periods,  dra-ma  to  the  same  scale.     (Ruckert.) 
A.  At  the  period  of  maximal  size  and  minimal  staining- capacity  (egg  3  mm.  in 
diameter).     B.  Later  period  (egg  13  mm.  in  diameter).     C.  At  the  close  of  ovarian 
life,  of  minimal  size  and  maximal  staining-power. 

of  the  egg.  At  first  they  are  small  and  stain  deeply  with  ordinary 
nuclear  dyes,  but  during  the  period  of  growth  they  undergo  a  great 
increase  in  size  and  at  the  same  time  lose  their  staining  capacity,* 
their  surface  being  increased  by  the  development  of  long  threads 
which  grow  out  in  every  direction  from  the  central  axis.  As  the  egg 
approaches  its  full  size,  the  chromosomes  diminish  in  size  and  are 
finally  reduced  to  minute  intensely  staining  bodies  which  take  part 
in  the  first  division  of  the  egg  preparatory  to  its  fertilisation  (Fig.  12). 
We  must  conclude  that  whereas  the  processes  of  destructive  meta- 
bolism or  dissimilation,  which  determine  the  activity  of  the  cell,  have 
*  Biickert,  cited  by  Wilson, 


THE  STRUCTURAL  BASIS  OF  THE  BODY  35 

their  immediate  seat  in  the  cytoplasm,  the  processes  of  constructive 
metabolism  which  lead  to  the  formation  of  new  material,  to  the 
chemical  and  morphological  building  up  of  the  cell,  are  carried  out  in 
or  by  the  intermediation  of  the  nucleus. 

HISTOLOGICAL  DIFFERENTIATION  OF  CELLS.  Even  within 
the  limits  of  a  single  cell,  differentiation  of  structure  can  take  place  by 
the  setting  apart  of  distinct  portions  of  the  cell  for  isolated  functions. 
Thus  in  an  organism  such  as  vorticella  the  cell  is  shaped  somewhat 
like  a  wine-glass,  the  stem  being  composed  of  a  spiral  contractile  fibre 
which  has  the  function  of  withdrawing  the  rest  of  the  organism  when 
necessary  towards  its  point  of  attachment.  The  main  portion  of  the 
cell  presents  at  its  free  extremity  a  part  which  is  the  seat  of  ingestion 
of  food,  and  is  therefore  spoken  of  as  the  '  mouth.'  This  is  surrounded 
by  a  circle  of  cilia  whose  function  it  is  to  set  up  currents  in  the  sur- 
rounding fluid  and  so  favour  the  passage  of  food  particles  towards  the 
mouth.  Food  when  ingested  at  this  end  passes  only  a  short  distance 
into  the  body  of  the  vorticella.  Here  fluid  is  secreted  around  it  which 
serves  for  its  digestion.  This  portion  of  the  cell  may  therefore  be 
regarded  as  the  alimentary  canal  or  stomach.  The  indigestible  residue 
of  the  food  is  excreted  in  close  proximity  to  the  mouth.  In  addition 
to  these  organs  we  have  the  usual  differentiation  of  the  protoplasm 
into  an  external  and  internal  layer,  and  the  development  within  the 
protoplasm  of  contractile  vacuoles  which  serve  to  keep  up  a  circulation 
of  fluid  and  therefore  to  pass  the  products  of  digestion  through  all 
parts  of  the  cell  body.  Within  the  limits  of  the  single  cell  which  forms 
the  vorticella  we  may  therefore  speak  of  organs  for  contraction,  for 
digestion,  for  circulation,  and  so  on. 

The  organs  which  are  thus  formed  in  unicellular  animals  or  plants 
can  be  divided  into  two  classes,  namely,  (1)  temporary  organs,  which 
are  formed  out  of  a  common  structural  basis  and  can  therefore  be 
replaced  at  any  time  by  the  cytoplasm  if  destroyed.  Examples  of  such 
organs  are  the  cilia,  the  commonest  motor  apparatus  of  unicellular 
organisms  ;  the  pseudopodia,  which,  as  we  have  seen,  can  be  made  and 
destroyed  at  will  ;  the  mouth  of  animals  such  as  Volvox  or  Vorticella  ; 
and  the  stinging  cells  or  nectocysts,  which  surround  the  mouth  of  many 
of  these  animals  and  serve  to  par.ilyse  or  kill  the  smaller  living  orga- 
nisms which  are  brought  by  the  cilia  within  reach  in  order  that 
they  may  serve  as  food.  In  contradistinction  to  these  organs  are 
(2)  a  number  of  others  which  must  be  regarded  as  permanent.  These 
cannot  be  formed  by  differentiation  from  the  cytoplasm  of  the  cell, 
but  are  derived  by  the  division  of  pre-existing  organs  of  the  same 
character,  and  are  therefore  transmitted  from  one  generation  to 
another.  As  examples  of  such  cell  organs  may  perhaps  be  mentioned 
the  nucleus,  with  its  chromosomes,  and  the  plastids,  of  which  the 


36  PHYSIOLOGY 

chloroplasts  of  vegetable  cells  are  the  most  conspicuous.  Certain  cell 
organs  may  fall  into  either  class.  Thus,  the  contractile  vacuoles  are 
sometimes  derived  by  the  division  of  the  pre-existing  vacuoles  in  a 
previous  generation,  at  other  times  are  certainly  formed  out  of  the 
common  cytoplasm.  The  centrosome,  a  small  particle  generally 
situated  in  the  cytoplasm,  which  plays  an  important  part  in  cell 
division,  is  generally  derived  by  the  division  of  a  pre-existing  centro- 
some, but  under  certain  conditions  and  in  some  organisms  can  be 
developed  in  situ  in  the  cytoplasm  itself. 

The  possibility  of  histological  differentiation  and  of  the  adaptation 
of  structure  to  definite  functions  becomes  much  more  pronounced 
as  we  pass  from  the  unicellular  to  the  multicellular  organisms  or 
metazoa.  The  lowest  of  the  metazoa,  such  as  the  sponges,  consist  of 
little  more  than  an  aggregation  or  colony  of  cells.  All  the  cells  are 
still  bathed  with  the  outer  fluid,  and  any  differentiation  of  structure 
or  function  seems  to  be  entirely  conditioned  by  the  position  of  the  cell. 
In  the  coelenterata  the  differentiation  is  already  much  more  marked. 
The  hydra,  one  of  the  simplest  of  the  group,  consists  of  a  sac  formed 
of  two  layers  of  cells  and  attached  by  a  stalk  to  some  firm  basis. 
Round  the  mouth  of  the  sac  is  a  circle  of  tentacles.  The  inner  layer, 
or  hypoblast,  represents  the  digestive  and  assimilatory  layer,  while 
the  epiblast,  or  outer  layer,  is  modified  for  the  purposes  of  protection,  of 
reception  of  stimuli,  and  of  motor  reaction.  In  the  jelly-fish  the  differen- 
tiation of  the  outer  layers  leads  to  the  formation  of  the  first  trace  of  a 
nervous  system,  i.e.  a  system  fitted  especially  for  the  reception  of  stimuli 
and  for  their  transmission  to  the  reactive  tissues,  namely,  the  muscles. 

In  all  these  classes  of  animals  the  external  medium  of  every  cell 
forming  the  organism  is  the  sea-water  or  other  medium  in  which  they 
live.  This  can  penetrate  through  the  interstices  between  the  cells, 
and  every  cell  is  therefore  exposed  to  all  the  possible  variations  which 
may  occur  in  the  composition  of  the  surrounding  medium.  A  great 
step  in  evolution  was  accomplished  with  the  formation  of  the  coelomata, 
the  class  to  which  all  the  higher  animals  belong.  In  these,  by  the  forma- 
tion of  a  body  cavity  containing  fluid,  an  internal  medium  is  provided 
for  all  the  working  cells  of  the  body.  The  composition  of  this  internal 
medium  is  maintained  constant  by  the  activity  of  the  cells  in  contact 
with  it,  and  the  stress  of  sudden  changes  in  the  chemical  composition  of 
the  surrounding  medium  is  borne  entirely  by  the  outer  protective  layer 
of  epiblast  cells.  These  are  rendered  more  or  less  impermeable  by  the 
secretion  on  their  surfaces  of  a  cuticular  layer,  and  only  such  of 
the  constituents  of  the  surrounding  medium  are  allowed  to  enter  the 
organism  as  can  be  utilised  by  it  for  building  up  its  living  protoplasm. 
Out  of  the  coelom  is  later  on  formed  a  circulatory  system  which,  by  the 
circulation  of  the  ccelomic  fluid  or  of  blood  throughout  the  whole 


THE  STRUCTURAL  BASTS  OF  THE  BODY  37 

body,  can  procure  a  still  more  perfect  uniformity  in  the  chemical 
conditions  to  which  every  cell  is  exposed.  It  is  not  till  much  later 
that  the  orfjanism  achieves  an  independence  of  external  conditions  of 
temperature.  In  the  mammalia,  by  means  of  the  reactive  nervous 
system,  the  heat  produced  in  every  vital  activity  by  the  chemical 
changes  of  combustion  and  disintegration  is  so  balanced  against  the 
heat  lost  through  the  external  surface  to  the  environment  that  the 
temperature  of  the  internal  fluid  is  maintained  practically  constant. 
One  of  the  main  results  of  the  differentiation  of  function  and  structure 
is  therefore  a  gradual  setting  free  of  the  majority  of  the  cells  of  the 
body  from  the  influence  of  variations  in  the  environment ;  and  in  the 
highest  type  of  all  animals,  in  man,  this  independence  of  external  con- 
ditions is  carried  to  a  much  further  extent  by  conscious  adaptations, 
such  as  the  use  of  clothes,  dwellings,  artificial  heating,  and  so  on. 

The  differentiation  of  the  cells  which  compose  the  organs  of  the 
body  is  determined  in  the  first  place  by  the  different  conditions  to 
which  they  are  exposed  in  virtue  of  their  positions  in  the  course  of 
development.  All  the  higher  animals  may  be  considered  as  built  in 
the  form  of  a  tube,  the  external  surface  of  which  is  modified  for  the 
purpose  of  defence  and  for  adaptation  to  changes  in  the  environ- 
ment. From  this  layer  there  are  developed  not  only  the  protective 
cuticle,  but  also  the  organs  of  motor  reaction,  namely,  the  special 
senses  and  the  nervous  system.  The  internal  surface  of  the  tube 
is  modified  for  purposes  of  alimentation.  From  it  are  developed  all 
those  structures  which  serve  for  the  digestion  of  the  food-stuffs,  for 
their  absorption  into  the  common  circulating  fluid,  for  their  elabora- 
tion after  absorption,  and  their  preparation  for  utilisation  by  other 
cells  of  the  body.  Between  these  two  surfaces  are  situated  the  support- 
ing tissues  of  the  body  as  well  as  the  organs  for  the  conversion  of 
the  potential  energy  of  the  body  into  motion  and  work,  namely,  the 
muscles.  Here  also  is  the  coelom  or  body  cavity,  represented  in  the 
higher  animals  by  the  pleural  and  peritoneal  cavities.  The  alimentary 
canal  projects  for  a  considerable  part  of  its  course  into  this  coelom, 
being  attached  to  the  body  wall  only  by  one  side.  From  the  ccplom 
is  also  developed  the  blood  vascular  system,  surrounded  by  contractile 
and  connective  cells  which  maintain  a  constant  circulation  of  the 
blood  throughout  the  body.  By  this  differentiation  the  body  becomes 
divided  into  a  number  of  organs,  each  of  which  is  composed  of  like  cells, 
modified  for  a  common  function  and  bound  together  by  connective 
tissue,  the  latter  serving  also  to  carry  the  blood-vessels  which  convey 
the  common  medium  for  the  working  cells.  In  the  study  of  physiology 
our  task  consists,  firstly,  in  the  description  of  the  special  part  taken 
by  each  organ  in  the  general  functions  of  the  body,  and,  secondly,  in 
the  determination  of  the  liniitinu  conditions  of  such  functions  and  of  the 


38  PHYSIOLOGY 

physical  and  chemical  factors  which  determine  them.    Finally,  we  have 

to  endeavour  to  form  a  complete  conception  of  the  chain  of  events 
concerned  in  the  discharge  of  each  function  and  of  their  causal  nexus. 
We  have  compared  the  higher  animal  in  the  foregoing  lines  to  a 
colony  of  cells,  and  we  often  speak  of  an  isolated  cell  of  the  body  as  if 
it  were  an  independent  elementary  organism.  A  better  term  for  such 
an  aggregation  of  cells  as  presented  by  the  higher  animals  is  not 
however  '  cell  coloiiv,'  but  '  cell  state,'  since,  just  as  in  the  state 
politic,  no  cell  is  independent  of  the  activities  of  the  others,  but  the 
autonomy  of  each  is  merged  into  the  life  of  the  whole.  With  increasing 
differentiation  there  is  increasing  division  of  function  among  the 
various  members  of  the  state,  and  each  therefore  becomes  less  and 
less  fitted  for  an  independent  existence  or  for  the  discharge  of  all  its . 
vital  functions.  The  more  highly  civilised  a  man  becomes  and  the 
greater  his  specialisation  in  the  work  of  the  community,  the  smaller 
chance  would  he  have  of  existing  on  a  desert  island.  Thus  the  life  of 
the  organism  is  essentially  composed  of  and  determined  by  the  recip- 
rocal actions  of  the  single  elementary  parts.  It  is  evident  that,  if  the 
process  of  specialisation  has  gone  far  enough,  a  discussion  whether 
each  unit  has  or  has  not  an  independent  life  is  beside  the  mark,  since 
it  cannot  possibly  exist  apart  from  the  activities  of  the  other  cells. 
Of  late  years  histologists  have  brought  forward  evidence  which  seems 
to  imply  that  an  actual  structural  interaction  exists,  in  addition  to 
the  functional  dependence  which  is  a  necessary  resultant  of  specialisa- 
tion. Even  in  the  case  of  plant  cells  with  their  thick  cellulose  walls, 
fine  bridges  of  protoplasm  can  be  made  out  passing  from  one  cell  to 
another  through  pores  in  the  cellulose  wall.  In  animals  protoplasmic 
bridges  are  known  to  exist  joining  up  adjacent  cells  in  unstriated 
muscle,  epithelium  and  cartilage  cells,  and  in  some  nerve-cells.  The 
conclusion  has  therefore  been  drawn  that  the  inorphological  unit  is 
not  the  cell,  but  the  whole  organism,  and  that  the  division  of  the 
common  cytoplasm  into  cells  is  merely  a  question  of  size  and  con- 
venience. There  can  be  no  doubt  that  the  determining  factor  in  the 
division  of  cells  is  their  growth  ;  the  cell  divides  because  it  grows. 
With  increased  mass  of  living  substance  it  is  necessary  to  provide  for 
increase  of  surface  both  of  cytoplasm  and  of  nucleus.  Whether  all  the 
tissues  of  the  higher  animals  remain  in  structural  contiiniity  by  proto- 
plasmic bridges,  &c.,  must  be  to  us  a  matter  of  indifference,  since  all 
that  is  necessary  for  the  interdependent  working  of  the  different  cells 
of  the  body  is  a  functional  continuity,  and  this  in  the  higher  animals 
is  effected  by  the  presence  of  a  common  circulating  fluid  and  a  reactive 
nervous  system  connected  by  conducting  strands  with  all  the  cells 
of  the  body. 


CHAPTER  III 
THE    MATERIAL    BASIS    OF    THE    BODY 

SECTION   I 

THE   ELEMENTARY  CONSTITUENTS   OF 
PROTOPLASM 

The  material  basis  of  which  living  organisms  are  built  up  is  derived 
from  the  surrounding  medium,  and  the  elements  which  compose  the 
framework  of  the  body  must,  therefore  be  identical  with  those  found 
in  the  earth's  crust.  Not  all  the  elements  are  so  utilised  in  the  forma- 
tion of  living  matter.  Every  living  organism  without  exception 
contains  the  following  elements  :  carbon,  hydrogen,  oxygen,  nitrogen, 
sulphur,  phosphorus,  chlorine,  potassium,  sodium,  calcium,  magne- 
sium, and  iron.  In  addition  to  these  twelve  elements  others  are  found 
in  certain  organisms,  sometimes  to  a  large  extent,  but  it  is  not  known 
how  far  they  are  necessary  to  the  proper  development  of  these  orga- 
nisms, and  it  is  certain  that  they  do  not  form  an  integral  constituent 
of  all  organisms.  Of  these  elements  we  may  mention  especially  silicon, 
iodine,  fluorine,  bromine,  aluminium,  manganese,  and  copper.  Dealing 
with  the  first  class,  i.e.  those  which  are  essential  to  all  forms  of  life, 
we  find  that  their  relative  proportions  in  living  organisms  have  little 
or  no  relation  to  their  proportions  in  the  environment  of  the  organisms. 
Their  presence,  however,  in  the  latter  is  a  necessary  condition  of  life. 
In  the  case  of  plants  which  have  a  fixed  habitat  and  cannot  move  in 
search  of  food,  the  growth  of  the  plant  is  limited  by  the  amount  of  the 
necessary  element  which  is  present  in  smallest  quantities  in  the  sur- 
rounding medium.  This  is  what  is  meant  by  the  agriculturist's  '  Law 
of  the  Mininumi.'  Of  the  elements  derived  from  the  earth's  crust, 
those  present  in  the  smallest  amounts  in  most  soils  are  potassium, 
nitrogen,  and  phosphorus.  The  growth  of  a  crop  in  any  given  soil  is 
determined  by  the  amount  of  that  one  of  these  three  substances  which 
is  present  in  smallest  quantities,  and  the  aim  of  agriculture  is  to  supply 
to  every  soil  the  ingredient  which  is  present  in  minimal  amount. 

Carbon  forms  the  greater  part  by  weight  of  the  solid  constituents 
of  living  protoplasm.  The  proximate  constituents  of  living  organisms 
are   practically  all  carbon  compounds,   so  that  organic  chemistry, 

39 


40  PHYSIOLOGY 

which  was  originally  the  chemistry  of  substances  produced  by  the 
agency  of  living  organisms,  has  come  to  be  synonymous  with  the 
chemistry  of  carbon  compounds.  The  carbon  compounds  which  make 
up  the  living  cell  are  combustible,  i.e.  they  can  unite  with  oxygen 
to  form  carbon  dioxide  with  the  evolution  of  heat.  In  the  inorganic 
world  practically  all  the  carbon  occurs  in  a  completely  oxidised  form, 
namely,  carbon  dioxide.  A  small  amount,  4  parts  in  10,000,  is  present 
in  the  atmosphere,  while  vast  quantities  are  buried  in  the  crust  of  the 
earth  as  carbonates  of  the  alkaline  earths,  &c.,  in  the  form  of  chalk 
and  limestone.  In  this  condition  the  carbon  dioxide  is  practically 
removed  from  the  life  cycle,  the  whole  of  the  carbon  contained  in  the 
tissue  of  living  beings,  whether  plant  or  animal,  being  derived  from 
the  minute  proportion  of  carbon  dioxide  present  in  the  atmosphere. 
The  energy  for  the  conversion  of  carbon  dioxide  into  the  oxidisable 
forms  with  high  potential  energy,  which  make  up  the  tissues  of  plants 
and  animals,  is  furnished  by  the  sun's  rays.  The  machine  for  the 
conversion  of  the  radiant  energy  into  the  potential  chemical  energy  of 
the  carbon  compounds  is  represented  by  the  chlorophyll  corpuscles  in 
the  green  parts  of  plants.  In  these  corpuscles,  under  the  influence  of  the 
sun's  rays,  the  carbon  dioxide  of  the  atmosphere,  together  with  water, 
is  converted  into  carbohydrates,  viz.  starch  (CeH^oOs),  and  the  oxygen 
liberated  in  the  process  is  set  free  into  the  surrounding  atmosphere. 

6CO2  +  5H2O  =  CeHioOs  +  6O2. 

In  this  process  a  large  amount  of  energy  is  absorbed,  an  energy 
which  can  be  set  free  later  by  the  oxidation  of  the  starch  to  carbon 
dioxide.  In  the  oxidation  of  one  gramme  of  starch  about  4500  calories 
are  evolved,  and  this  represents  also  the  measure  of  the  solar  energy 
which  must  be  absorbed  by  the  chlorophyll  corpuscle  in  the  process 
of  formation  of  starch  from  the  carbon  dioxide  of  the  atmosphere. 
By  this  means  the  world  of  life  is  provided  with  a  source  of  energy. 
At  the  expense  of  the  energy  of  the  starch  further  synthetic  processes 
are  carried  out.  By  the  oxidation  of  a  part  of  the  carbohydrates, 
sufficient  energy  may  be  supplied  to  deoxidise  other  portions  of  the 
carbohydrates  with  the  production  of  fats.     Thus 

SCsHiaOe  —  8O2  =  CisHggO.^ 
(Glucose)  (Stearic  acid) 

The  potential  energy  of  a  fat  is  still  greater  than  that  of  a  carbohydrate, 
one  gramme  of  fat  giving  on  complete  combustion  to  carbonic  acid 
and  water  as  much  as  9000  calories.  By  the  introduction  of  ammonia 
groups  (NH2)  into  the  molecules  of  fatty  acids,  amino-acids  may 
be  formed,  from  which  the  complex  proteins  are  built  up  to  form  the 
chief  constituents  of  the  living  protoplasm. 


THE  ELEMENTARY  CONSTITUENTS  OF  PROTOPLASM    41 

The  synthesis  of  carbon  compounds  from  the  inert  carbon  dioxide 
of  the  atmosphere  can  be  effected  only  by  chlorophyll  corpuscles. 
All  animals  take  in  carbon,  hydrofj;en,  nitrogen,  oxygen,  and  sulphur 
in  the  form  of  the  carbohydrates,  fats,  and  proteins  which  have  been 
built  up  in  the  living  plants.  In  the  animal  organi.sm  these  food-stuffs 
serve  as  sources  of  energy,  undergoing  a  gradual  oxidation,  and  finally 
leave  the  body  in  the  form  of  carbon  dioxide,  water,  ammonia  or 
some  related  compound,  and  sulphates.  A  sharp  line  of  demarcation 
has  therefore  often  been  drawn  between  the  metabolism  of  plants  and 
animals,  plants  being  regarded  as  essentially  assimilatory  in  character 
while  animals  are  dissimilatory,  utilising  the  stores  of  energ}^  which 
have  been  accumulated  by  the  plant.  There  is,  however,  no  sharp 
line  of  demarcation.  Although,  generally  speaking,  the  green  plant 
breaks  up  carbon  dioxide,  giving  off  oxygen  and  storing  up  carbon 
compounds,  and  the  animal  taking  in  carbon  compounds  oxidises 
them  with  the  help  of  the  oxygen  of  the  atmosphere  to  carbon  dioxide, 
which  is  redischarged  into  the  surrounding  medium  and  is  available 
for  further  assimilation  by  plants,  yet  this  process  of  respiration  is 
common  to  all  living  organisms,  whether  plants  or  animals.  In  the 
green  plant  it  may  be  masked  by  the  assimilatory  process  occurring 
under  the  influence  of  the  sun's  rays,  but  in  the  dark  all  parts  of  the 
plant,  and  in  the  light  all  parts  which  are  free  from  chlorophyll, 
display  a  process  of  respiration,  i.e.  they  are  constantly  taking 
up  oxygen  from  the  atmosphere  and  using  it  for  the  oxidation  of 
carbon  compounds  in  their  tissues,  with  the  production  of  carbon 
dioxide. 

The  sum  total  of  the  processes  of  life  tend,  therefore,  to  maintain 
a  constant  proportion  of  carbon  dioxide  and  oxygen  in  the  atmosphere, 
the  decomposition  of  carbon  dioxide  by  the  green  plants  being  balanced 
by  the  oxidation  of  the  carbon  compounds  and  the  continual  discharge 
of  carbon  dioxide  by  animals.  It  is  not  certain,  however,  that 
this  balance  will  be  maintained  throughout  all  time.  As  Bunge  has 
pointed  out,  there  are  cosmic  factors  at  work  which  are  apparently 
tending  to  cause  a  constant  diminution  in  the  quantity  of  carbon  dioxide 
in  the  atmosphere,  which  alone  is  of  value  to  the  plant.  One  of  these 
factors  is  the  variable  affinity  of  the  silica  and  carbon  dioxide  respec- 
tively for  the  chief  bases  of  the  earth's  crust.  At  a  high  temperature 
silica  can  displace  carbon  dioxide  from  its  compounds.  Thus  chalk 
heated  with  silica  will  give  rise  to  calcium  silicate  with  the  evolution 
of  carbon  dioxide.  At  an  early  geological  epoch,  therefore,  it  is  i)robable 
that  the  greater  part  of  the  silica  was  present  in  combination  with 
bases  and  that  the  proportion  of  carbon  dioxide  in  the  atmosphere 
was  very  much  higher  than  it  is  now.  At  temjx'ratures  at  present 
ruling  on  the  earth's  surface  carbon  dioxide  is  a  stronger  acid  than 


42  PHYSIOLOGY 

silica.  The  action  of  water  charged  with  carbon  dioxide  on  a  silicate 
is  to  cause  its  gradual  decomposition  with  the  formation  of  carbonate 
and  sihca.  Both  these  products,  being  insoluble,  are  deposited  as 
part  of  the  earth's  crust,  the  silica  in  the  form  of  sandstone,  the  carbo- 
nate as  chalk  or  limestone.  The  carbon  dioxide  is  being  constantly 
removed  by  water  from  the  atmosphere  and  being  locked  up  in  this 
way  in  the  earth's  crust,  the  process  of  separation  of  calcium  carbonate 
being  aided  to  a  marked  extent  by  the  agency  of  living  organisms 
themselves.  The  whole  of  the  extensive  deposits  of  limestone  and 
chalk  have  been  separated  from  the  sea-water  by  the  action 
of  living  organisms.  With  the  cooling  of  the  earth's  crust  which 
is  supposed  to  be  going  on,  the  discharge  of  carbon  dioxide  by  vol- 
canoes must  get  less  and  less,  so  that  one  can  conceive  a  time  when 
the  whole  of  the  carbon  dioxide  will  be  bound  up  with  bases  in 
the  earth's  crust,  and  life,  without  any  source  of  carbon,  must  become 
extinct. 

Hydrogen  exists  almost  exclusively  in  the  form  of  water.  In  this 
form  it  is  taken  up  by  plants  and  animals,  with  the  exception  of  a 
small  proportion  absorbed  in  the  form  of  ammonia.  In  this  form 
too  it  is  discharged  by  living  organisms.  Oxygen  is  the  only  element 
which,  in  all  the  higher  organisms  at  any  rate,  is  taken  up  in  the  free 
state.  It  forms  one-fifth  of  the  atmosphere  and,  as  the  oxides  of 
the  various  metals,  a  considerable  fraction  of  the  earth's  crust.  It 
takes  a  position  apart  from  the  other  food-stuffs  in  that  its  presence 
is  the  essential  condition  for  the  utilisation  of  their  potential  energy. 
In  the  living  cells  it  combines  with  the  oxidisable  compounds  formed 
by  the  agency  of  the  living  protoplasm,  with  the  production  of  carbon 
dioxide  and  water,  and  the  evolution  of  energy.  This  process  is  spoken 
of  as  respiration. 

Like  the  three  elements  we  have  already  considered,  nitrogen  is 
also  derived  directly  or  indirectly  from  the  surrounding  atmosphere. 
In  consequence  of  its  feeble  combining  power  for  other  elements 
and  the  instability  of  its  compounds,  very  little  nitrogen  is  to 
be  found  in  the  combined  state  in  the  earth's  crust,  whereas  it 
constitutes  four-fifths  of  the  atmospheric  gases.  It  can  be  taken  up 
by  most  plants  only  in  the  form  of  ammonia,  nitrites,  or  nitrates.  To 
animals  these  compounds  are  useless,  and  the  only  source  of  nitrogen 
to  this  class  is  the  protein  which  has  been  built  up  by  the  agency  of 
the  plant  cell.  Since  nitrogen  in  the  free  state  is  useless  to  nearly  all 
living  organisms,  the  existence  of  life  must  depend  on  the  amount  of 
combined  nitrogen  which  is  available.  In  view  of  the  small  tendency 
presented  by  this  element  to  enter  into  combination,  it  becomes 
interesting  to  inquire  into  the  source  of  the  combined  nitrogen  which 
is  the  common  capital  of  the  living  kingdom.  There  are  certain  cosmic 


THE  ELEMENTARY  OONSTTTTTENTS  OF  PROTOPLASM    43 

factors  which  result  in  the  production  of  combined  nitrogen.  The 
passage  of  electric  sparks  or  of  the  silent  discharge  through  moist 
air  leads  to  the  production  of  ammonium 
nitrite. 

N2  +  2H2O  =  NH4NO2. 

Every  thunderstorm,  therefore,  will  result  in 
the  production  of  small  quantities  of  ammo- 
nium nitrite,  which  will  be  washed  down  with 
the  rain  and  serve  as  a  source  of  combined 
nitrogen  to  the  soil.  Every  decaying  vege- 
table or  animal  tissue  serves  as  a  source  of 
ammonia,  so  that  from  various  causes  the 
soil  may  contain  nitrogen  in  the  form  of 
ammonia  or  of  ammonium  nitrite.  These 
forms  of  combined  nitrogen  are  not,  however, 
suitable  for  all  classes  of  plants.  Most  moulds 
can  assimilate  ammonia  as  ammonium  car- 
bonate or  as  amino-acids  or  amines,  provided 
that  they  are  supplied  *at  the  same  time  with 
sugar,  the  oxidation  of  which  will  serve  them 
as  a  source  of  energy.  Some  moulds,  many  of 
the  higher  plants,  and  especially  the  Gramineae, 
which  include  the  food-producing  cereals, 
require  their  nitrogen  in  the  condition  of 
nitrates.  It  is  necessary,  therefore,  that  the 
ammonia  or  nitrites  in  the  soil  shall  be  con- 
verted into  this  highly  oxidised  form.  This 
conversion  is  effected  by  a  group  of  micro- 
organisms. There  are  a  number  of  bacteria 
(bacterium  nitrosomonas)  which  have  the 
power  of  converting  ammonia  into  nitrites. 
Others  (bacterium  nitromonas)  convert  nitrites 
into  nitrates.  If  sewage  matter  rich  in 
ammonia  is  allowed  to  percolate  through  a 
cylinder  packed  with  coke  and  the  process  be 
continued  for  several  weeks,  it  is  found  after  a 
time  that  in  its  passage  through  the  filter  the 
fluid  has  lost  its  ammonia  and  contains  the 
whole  of  its  nitrogen  in  the  form  of  nitrate. 

If  the  cylinder  be  tapped  (Fig.  13)  half-way  down,  say  at  A,  the  fluid 
will  be  found  to  contain,  not  nitrates,  but  nitrites.  In  this  conversion 
the  two  kinds  of  microbes  mentioned  above  are  concerned.  At  the  top 
of  the  cylinder  the  nitrous  bacterium  is  present,  in  the  bottom  oi  the 


l''iG.  13.  Arrangt'iiunt  for 
studying  the  nitritica- 
tion  of  sewage.  (Miss 
H,  CnicK.) 


44  PHYSIOLOGY 

cylinder  the  nitrate  bacterium  is  present.  The  conversion  of  ammonia 
into  nitrates  by  the  agency  of  bacteria  has  been  made  the  basis  of  a 
method  of  treatment  of  sewage  which  is  now  very  largely  employed. 
These  different  bacteria  play  an  important  part  in  all  soils  in  pre- 
paring them  for  the  cultivation  of  crops. 

Is  the  total  capital  of  combined  nitrogen  which  is  worked  over 
by  these  bacteria  and  utilised  by  the  whole  living  world  confined  to 
the  small  quantities  produced  by  atmospheric  discharges  ?  Of  late 
years  definite  evidence  has  been  brought  forward  that  such  is  not  the 
case  and  that  organisms  exist  which  can  utilise  and  bring  into  com- 
bination the  free  atmospheric  nitrogen  itself.  Thus  certain  soils  have 
been  found  to  undergo  a  gradual  enriching  in  nitrogen  although  no 
nitrogenous  manure  has  been  applied  to  them.  Winogradsky  has 
shown  that  this  fixation  of  nitrogen  by  soils  is  effected  by  a  distinct 
micro-organism,  which  he  isolated  by  growing  on  gelatinous  silica  free 
from  any  trace  of  combined  nitrogen,  so  that  the  organism  had  to 
procure  its  entire  nitrogen  from  the  atmosphere.  Under  such  con- 
ditions the  numerous  other  micro-organisms  of  the  soil  died  of  nitrogen 
starvation,  and  only  the  microbe  survived  which  was  able  to  utilise 
free  nitrogen.  This  organism,  which  he  called  Clostridium  pasteurianum, 
grows  well  on  sugar  solution  if  free  from  ammonia  and  enriches  the 
solution  with  combined  nitrogen.  It  is  anaerobic,  i.e.  only  grows 
in  the  absence  of  oxygen.  In  the  soil,  where  oxygen  is  constantly 
present,  it  occurs  associated  in  a  sort  of  symbiosis  with  two  species 
of  bacteria  which  are  aerobic  and  protect  it  from  the  surrounding 
oxygen.  The  mechanism  by  which  this  organism  is  able  to  fix  free 
nitrogen,  and  the  nature  of  the  first  product  of  the  assimilation  are  not 
yet  ascertained.  Such  an  assimilation  will  serve  to  the  organism  as  a 
source  of  energy,  since  the  application  of  heat  is  necessary  for  the  dis- 
sociation either  of  ammonium  nitrite  or  of  nitrous  acid  into  nitrogen 
and  water,  as  is  seen  from  the  following  equation  : 

HNOgAq.  +  308  Cal.  =  H  +  N  +  O2  +  Aq. 
NH^NOgAq.  +  602  Cal.  =  2N  +  4H  +  20  +  Aq. 

In  addition  to  this  spontaneous  fixation  of  nitrogen  by  humus,  a 
method  has  long  been  known  to  farmers  by  which  the  fertility  of  a 
soil  can  be  increased  without  the  application  of  nitrogenous  manures. 
If  a  plot  of  land  is  to  be  left  fallow  it  is  a  very  usual  custom  to  sow  it 
with  some  leguminous  crop  such  as  sainfoin.  Careful  experiments  by 
Boussingault,  Lawes  and  Gilbert,  and  others  have  shown  that  the 
growth  of  almost  any  leguminous  crop  in  a  soil  poor  in  nitrogen  may 
result  not  only  in  the  production  of  a  crop  containing  much  combined 
nitrogen,  but  also  in  an  actual  increase  of  nitrogen  in  the  soil  from 
which  the  crop  is  taken.   It  was  then  shown  by  the  last  two  observers, 


THE  EI.EMENTARY  CONSTITUENTS  OF  PROTOPLASM     4: 


as  well  as  by  Schloesing  and  Laurent,  that  the  power  of  a  leguminous 

crop  to  enrich  the  soil  with  nitrogen  was  dependent  oh  the  presence 

on  the  roots  of  certain  small  nodules  which  had  been  described  long 

before  by  Malpighi  (Fig.  14).  They  showed  also  that  the  production  of 

these  nodules  took  place  only  as  a  result  of  infection.     Beans  grown  in 

sterilised  sand  produced  a  plant  free  from  nodules,  which,  however, 

grew  very  scantily  unless  nitrogenous  manure  were 

added  to  the  sand.     Such  a  crop  derived  the  nitrogen 

for   its   growth   from   the   added   nitrogen,  the    total 

amount  of  which  in  the  soil  was  therefore  diminished 

by  the  crop.     If,  however,  the  sterilised  sand  were 

treated  with  an  infusion  of  root  nodules  from  another 

])lant  without  the  addition  of  any  combined  nitrogen 

at  all,  the  beans  developed  nodules  on  their  roots  and 

grew    luxuriantly,   and    at   the    termination    of   their 

growth   the   soil   was   richer  in  nitrogen  than  at  the 

commencement.       On    microscopic    examination    the 

protoplasm  which  makes  up  these   nodules    is   found 

to  be  swarming  with  small  rods  (Fig.  15),  and  it  was 

shown  by  Beyerinck  that  these  rods  are  bacteria  and 

can  be  cultivated  in  media  apart  altogether  from  the 

plant.      We  have    thus    an    example    of   a  class  of 

bacteria  which,  like    those    of    humus,    are    able    to 

assimilate  the  free  nitrogen  of  the  atmosphere,  but, 

unlike  them,  can  only  effect    this    assimilation  in  a 

condition    of    symbiosis,   i.e.  living    in    the    growing 

tissues  of  a  leguminous  plant.     Similar  nodules  have 

been  described  on  the  roots  of  other  plants  which 

can  grow  in  a  soil  free  from  combined  nitrogen,  e.g. 

conifers,    but    it    is    in    the    leguminosse    that    their 

presence  is  most  widespread. 

The  source  of  the  combined  nitrogen,  which  can  be  built  up  by 
plants  into  proteins  and  utilised  in  this  form  by  animals,  is  thus  not 
only  the  ammonium  nitrite  produced  by  the  agency  of  electric  dis- 
charges in  the  atmosphere,  but  also  the  free  nitrogen  of  the  atmosphere 
assimilated  by  various  types  of  bacteria. 

Sulphur  \&  found  in  all  soils  in  the  form  of  sulphates,  generally  of 
lime.  As  sulphates  it  is  taken  up  by  plants.  In  the  plant  cell  a  process 
of  deoxidation  takes  place  at  the  expense  of  the  energy  derived  either 
from  the  starch  or,  in  the  case  of  bacteria,  from  other  ingredients  of 
their  food-supply.  It  is  built  up,  together  with  nitrogen,  carbon,  and 
hydrogen,  to  form  sulphur  derivatives  and  amino-acids  such  as  cystine, 
and  these,  together  with  other  amino-acids.  are  synthetised  to  form 
proteins.    Practically  the  whole  of  the  sulphur  taken  in  by  animals  is 


Fig.  14.  Root  of 
vetch  with  nod- 
ules. 


46 


PHYSIOLOGY 


in  the  form  of  proteins.  It  shares  the  oxidation  of  the  protein  molecule 
in  the  animal  body  which  it  leaves  in  the  form  of  sulphates.  The 
output  of  sulphates  by  an  animal  can  therefore  be  regarded,  like  the 
nitrogen  output,  as  an  index  of  the  protein  metabolism.  It  is 
returned  to  the  soil  in  the  form  in  which  it  was  taken  by  the  plant, 
and  the  cycle  can  be  continuously  repeated. 

Iron,  although  forming  but  a  minute  proportion  of  the  material 
basis  of  living  organisms  (the  whole  body  of  man  contains  only  six 


Fig.  15.     Section  of  a  root  nodule  of  Dorychnium.     (Vttillemin.) 
a,  cortical  tissue ;  h,  cells  containing  bacteria. 


grammes),  is  nevertheless  indispensable  for  the  maintenance  of  life. 
It  is  necessary,  for  instance,  in  two  important  functions,  viz.  the 
formation  of  chlorophyll  in  the  green  plant  and  the  respiratory  process 
in  the  higher  animals.  Although  iron  forms  no  part  of  the  chloro- 
phyll molecule,  plants  grown  in  the  absence  of  this  substance  remain 
etiolated,  but  form  chlorophyll  if  the  smallest  trace  of  iron  is  added 
to  the  soil  in  which  they  are  growing  or  even  if  the  leaves  are  washed 
with  a  very  dilute  solution  of  an  iron  salt.  In  animals  iron  forms  an 
essential  constituent  of  haemoglobin,  the  red  colouring-matter  of  the 
blood,  whose  office  it  is  to  carry  oxygen  from  the  lungs  to  the  tissues. 
It  is  probable  too  that  the  minute  traces  of  iron  in  protoplasm  exercise 
an  important  function  in  the  processes  of  oxidation  which  are  con- 
tinually going  on.  Even  in  the  inorganic  world  iron  plays  the  part  of 
an  oxygen  carrier.  In  the  earth's  crust  it  occurs  as  ferrous  salts  and 
as  ferric  oxide.    The  ferrous  silicate,  for  instance,  may  be  decomposed 


THE  ELEMENTARY  CONSTITUENTS  OF  PROTOPLASM    47 

by  water  containing  carbon  dioxide  into  silica  and  ferrous  carbonate  ; 
the  latter  then  absorbs  oxygen  from  the  atmosphere,  liberating  carbon 
dioxide  and  forming  ferric  oxide.  In  the  presence  of  decomposing 
organic  matter,  the  ferric  oxide  parts  with  its  oxygen  to  oxidise 
the  organic  substances  and  is  converted  once  more  into  ferrous 
carbonate,  and  this  may  be  decomposed  by  the  oxygen  of  the  air 
as  before.  In  the  presence  of  sulphates  and  decomposing  organic 
matter  ferrous  sulphate,  which  is  first  formed,  undergoes  deoxidation 
to  ferrous  sulphide,  and  this  may  again  be  oxidised  to  sulphates  and 
ferric  salts  on  exposure  to  the  atmosphere,  so  that  both  the  sulphur 
and  the  iron  act  as  oxygen  carriers  between  the  atmosphere  and  the 
organic  matter.  Iron  is  obtained  by  plants  from  the  soil  as  ferrous  or 
ferric  salts.  In  the  protoplasm  it  is  built  up  into  highly  complex 
organic  compounds,  and  in  this  form  is  taken  up  by  animals.  It  is 
probable  that  the  main  requirements  of  the  animal  for  iron,  which  are 
very  small,  may  be  satisfied  entirely  at  the  expense  of  these  organic 
compounds,  but  there  can  be  little  doubt  that  the  animal  can,  if  need 
be,  also  utilise  the  iron  salts  present  in  its  food.  The  animal  proceeds 
extremely  economically  with  its  supply  of  iron.  Any  excess  of  iron 
above  that  needed  to  supply  the  iron  lost  to  the  body,  as  well  as  the 
latter,  is  excreted  almost  entirely  with  the  faeces  in  the  form  of  sul- 
phide. In  the  soil  this  undergoes  oxidation  and  returns  once  more  to 
the  form  in  which  it  was  originally  taken  up  by  the  plant. 

Phosphorus  is  absorbed  by  the  plant  as  phosphates.  In  the  cell 
protoplasm  it  is  built  up  with  fatty  acids  and  other  organic  radicals 
to  form  complex  compounds  such  as  lecithin,  a  phosphorised  fat,  and 
nuclein,  a  combination  of  phosphorus  with  nitrogenous  bases  of  great 
variety.  Both  lecithin  and  nuclein  are  essential  constituents  of  living 
protoplasm.  Practically  the  whole  of  the  phosphorus  income  of 
animals  is  represented  by  these  lecithin  and  nuclein  compounds. 
After  absorption  into  the  animal  body  they  are  broken  down  by  pro- 
cesses of  dissociation  and  oxidation,  with  the  production,  as  a  final 
result,  of  phosphates,  which  are  excreted  with  the  urine  or  faeces  and 
return  to  the  soil. 

Chlorine,  'potassium,  sodium,  calcium,  and  m/ignesium  are  taken 
up  by  the  plants  in  the  form  of  salts.  Although  playing  an  essential 
part  in  all  vital  processes,  they  do  not  seem  to  be  built  up  into  organic 
combination  with  the  protein  and  other  constituents  of  the  cell  proto- 
plasm. They  are  therefore  taken  up  also  by  animals  in  the  form  of 
salts,  and  as  such  are  again  excreted  with  the  urine. 

Little  is  known  about  the  significance,  if  any,  of  the  other  elements 
which  I  have  mentioned  as  occasional  constituents  of  living  beings. 
Silicon,  which  is  of  universal  distribution,  is  assimilated  as  siUca, 
probably  in  colloidal  solution,  and  is  distributed  in  minute  quantitiea 


48  PHYSIOLOGY 

through  all  plant  and  animal  tissues.  It  forms  a  very  large  percentage 
of  the  mineral  basis  of  grasses,  but  even  here  it  does  not  seem  to  be 
indispensable,  since  these  will  grow  in  a  medium  devoid  of  silica  as 
luxuriantly  as  under  normal  conditions. 

Fluorine  is  found  in  the  enamel  of  the  teeth  and  in  minute  traces 
in  other  tissues  of  the  body. 

Bromine,  though  present  in  quantity  in  some  seaweeds,  appears 
to  play  no  part  in  the  economy  of  higher  animals. 

Iodine  is  found  in  large  quantities  in  many  seaweeds  and  is  present 
as  an  organic  iodine  compound  in  the  skeleton  of  certain  horny  sponges. 
An  organic  iodine  compound  is  also  found  in  the  thyroid  gland  of  the 
higher  animals,  and  may  possibly  be  the  active  principle  by  means  of 
which  these  glands  are  able  to  affect  the  nutrition  of  the  whole  body. 
Iodine,  therefore,  would  seem  to  be  an  essential  constituent  of  the 
higher  animals. 

Aluminium  is  found  in  large  quantities  in  certain  lycopods.  Whether 
it  is  essential  to  their  growth  is  not  known. 

Copper  is  certainly  not  a  necessary  constituent  of  a  large  number 
of  plants  and  animals.  In  one  class,  the  cephalopods,  it  appears  to 
take  the  part  of  iron  in  the  formation  of  a  blood  pigment.  The  haemo- 
cyanine,  which  was  described  by  Fredericq,  plays  the  same  part  in  the 
blood  of  cephalopods  that  is  played  by  haemoglobin  in  the  blood  of 
vertebrates.  When  oxidised  it  is  of  a  blue  colour,  but  gives  off  its  oxygen 
and  is  reduced  to  a  colourless  compound  on  exposure  to  a  vacuum. 

Among  these  elementary  constituents  of  the  body,  a  definite  line 
of  demarcation  can  be  drawn  between  the  carbon  and  hydrogen  on 
the  one  hand  and  all  the  other  constituents  on  the  other.  The  first 
two  elements  are  built  up  in  a  deoxidised  form  into  the  living  structure 
of  the  protoplasmic  molecule.  The  products  of  their  complete  oxida- 
tion are  volatile,  namely,  carbon  dioxide  and  water,  and  leave  the 
body  in  these  forms.  The  nitrogen  set  free  by  the  breaking  down  of 
the  proteins  will  pass  off  as  free  nitrogen  or  as  ammonia.  The 
sulphuric  acid  formed  by  the  oxidation  of  the  sulphur  combines  with 
the  bases  to  form  non-volatile  salts.  We  may  therefore  divide  the 
ultimate  constituents  of  the  body  into  those  which  are  combustible 
and  are  driven  ofE  on  heating,  and  those  which  are  left  behind  as  the 
ash. 


SECTION  II 

THE  PROXIMATE  CONSTITUENTS   OF  THE 
ANIMAL   BODY 

In  spite  of  the  enormous  variety  of  the  proximate  constituents  of 
living  organisms,  they  are  all  members  or  derivatives  of  three 
classes  of  compounds.  Since  living  organisms  form  the  entire 
food  of  the  animil  kingdom,  a  study  of  these  proximate  con- 
stituents includes  the  ttudy  of  all  the  food-stuffs.  These  classes 
are  : 

(a)  Proteins,  containing  the  elements  carbon,  hydrogen,  nitrogen, 
oxygen,  and  sulphur  ;  in  some  cases  also  phosphorus. 

(b)  Fats,  containing  carbon,  hydrogen,  and  oxygen. 

(c)  Carbohydrates,  containing  carbon,  hydrogen,  and  oxygen,  the 
two  latter  elements  being  present  in  the  proportions  in  which  they 
form  water. 

THE  CHIEF  TYPES   OF  ORGANIC  COMPOUNDS  OCCURRING 
IN  THE   ANIMAL  BODY 

The  fxill  consideration  of  the  various  modifications  undergone  by  these 
tliree  classes  of  food-stuflfs  in  the  body,  especially  if  we  include  the  by-products 
occurring  both  in  plants  and  in  animal  metabolism,  involves  a  wide  knowledge 
of  organic  chemistry,  which  indeed  at  its  origin  was  simply  the  chemistrv  of 
the  products  of  liAnng  {i.e.  organised)  beings.  The  most  important  substances 
with  which  we  shall  have  to  deal  belong  to  a  comparatively  restricted  number 
of  groups.  For  the  convenience  of  the  reader  a  short  summary  of  the  relation- 
ships of  these  groups  to  one  another  and  to  the  hydrocarbons  is  given  here, 

THE  HYDROCARBONS  (Fatty  Series).  These  form  a  continuous  homo- 
logous series,  and  may  be  saturated  or  unsaturated.  Examples  of  the  saturated 
series  are : 

CH4       methane 

CoHg     ethane 

CsHg     propane 

C4H10    butane,  and  so  on, 

the  general  formula  for  the  group  being 

C'H2„4.2. 

These  paraffins,  the  lower  members  of  which  are  gaseous,  while  the  higher 
members  form  the  petroleum  ether,  the  heavy  petroleums,  vaseline,  and  the 
paraffin  wax  with  which  we  are  all  familiar,  are  entirely  inert  in  tlic  aniinol 
body.  If  taken  with  the  food  they  pass  through  the  alimentary  canal  un- 
changed. In  order  to  render  them  accessible  to  the  action  of  the  living  cell 
they  must  first  undergo  oxidation. 

49  4 


50  PHYSIOLOGY 

The  unsaturated  hydrocarbons  have  the  general  formulae  CuH2n,  C  H2,,  2> 

CH2„-4.  &c. 

Examples  of  the  first  two  groups  are  ethylene  CH2 

CH2 

and  acetylene  CH 

lil 
CH 

Derivatives  of  all  these  groups  occur  in  the  body. 

THE     ALCOHOLS.     The   first  product  of   the   oxidation   of   hydrocarbons 
is  the  series  of  bodies  known  as  the  alcohols.     Examples  of  tliese  are  : 


CH30H 

methyl 

alcohol 

C2H50H 

ethyl 

C3H70H 

propyl 

C4H90H 

butyl 

CfiHuOH 

amyl 

CeHiaOH 

capryl 

and  so  on. 

the  general  formula  for  the  group  being 

CuH2u  +  lOH. 

In  all  these  alcohols  the  OH  group  is,  so  to  speak,  more  mobile  than  the  other 
atoms  connected  with  the  carbons,  and  can  therefore  be  replaced  by  other 
substances  or  groups  with  comparative  ease.  In  this  respect  therefore  an 
alcohol  can  be  compared  to  water  HOH  or  to  an  alkaline  hydroxide  NaOH  or 
KOH.  The  best-known  example  of  the  group  is  ethyl  alcohol,  the  ordinary 
product  of  fermentation  of  sugar.  In  these  alcohols  the  OH  group  can  be 
replaced  by  Na.  Thus,  water  with  metallic  sodium  gives  sodium  hydroxide 
and  hydrogen  as  follows  : 

2H0H  +  2Na  =  2NaOH  +  Ho. 

In  the  same  way  alcohol  treated  with  metallic  sodium  gives  off  hydrogen,  and 
the  remaining  fluid  contains  sodium  ethylate,  thus  : 

2C2H6OH  +  2Na  =  2C2H50Na  +  H2 

(sodium  ethylate) 

On  the  other  hand,  the  OH  group  may  be  replaced  by  acid  radicals.  Thus,  if 
ethyl  alcohol  be  treated  with  phosphorus  pentachloride,  ethyl  chloride  is  formed 
together  vnth  phosphorus  oxycliloride  and  hydrochloric  acid.     Thus  : 

Et.OH  +  PClg  =  POCI3  +  HCl  +  Et.Cl 

(ethyl  chloride) 

With  concentrated  sulphmic  acid  the  reaction  is  similar  to  that  Avhich  obtains 
between  sodium  hydrate  and  this  acid,  and  we  have  formed  ethyl  sulphate  and 
water.     Thus : 

Et.OH  +  H2SO4  -  Et.HSOi  +  HOH 

If  alcohol  be  warmed  with  acetic  acid  and  strong  sulphiu-ic  acid,  among  the 
products  of  the  reaction  is  ethyl  acetate,  which  is  volatile,  and  therefore  passes 
off.     Thus : 

Et.OH  +  HC2H3O2  =  Et.CaHsOa  +  HOH. 

These  compounds  of  the  hydrocarbon  group  of  the  alcohol,  such  as  methyl, 
ethyl,  propyl,  &c.,  with  an  acid,  in  which  the  ethyl  takes  the  part  of  a  base, 
are  known  as  esters. 


PROXBIATE  CONSTITUENTS  OF  THE  ANIMAL  BODY    51 

An  ester  treated  with  an  alkali  is  decomposed  with  the  formation  of  an 
alkaline  salt  of  the  acid,  and  the  corresponding  alcohol  which,  being  volatile, 
is  given  off  on  warming  the  mixture.     Thus  : 

Et.CaHgOa  +  XaHO  =  XaCzHsOg  +  Et.OH. 

(ethyl  acetate)  (potassium  acetate)  (alcghol) 

This  process  of  decomposition  of  an  ester  with  the  formation  of  the  alkaline 
salt  of  an  acid  is  often  spoken  of  as  saponification,  i.e.  soap  formation,  though 
the  term  '  soap  '  is  applied  only  to  the  compounds  of  alkalies  with  the  higher 
fatty  acids.  The  series  of  alcohols  we  have  just  dealt  ^vith  containing  one 
OH  group  replaceable  by  metals  or  acid  radicals  are  known  as  monatomic 
alcohols.  If  in  the  molecule  of  the  paraffin  two  or  more  atoms  of  hydrogen 
have  been  replaced  by  the  group  OH,  we  speak  of  diatomic  or  polyatomic 
alcohols.  Thus,  derived  from  the  paraffin  propane  C'aHg  we  may  have  the 
monatomic  alcohol  C3H7OH,  propyl  alcohol,  or  the  triatomic  alcohol  C3H6  (OH3), 
which  is  known  as  glycerin,  or  glj-corol. 

Other  alcohols  of  physiological  importance  are  cholesterol  and  cetyl  alcohol. 
Cholesterol  is  a  monatomic  alcohol  with  the  formula  C27H45OH.  It  is  very 
complex  in  structiu-e,  and  belongs  to  the  aromatic  series.  Recent  work  points 
to  an  affinity  of  cholesterol  with  the  terpenes,  which  have  hitherto  been  found 
only  as  the  product  of  the  metabolism  of  plant  cells.  Cholesterol  is  a  constant 
constituent  of  protoplasm.  It  occurs  in  large  quantities  in  the  medullary 
sheath  of  nerves  ;  it  is  a  normal  constituent  of  bile  and  may  form  concretions 
(biliary  calculi)  in  the  gall  bladder.  In  combination  with  fatty  acids  it  is  an 
important  constituent  of  sebum  and  of  wool  fat. 

CH3 

I 
Another   alcohol — cetyl  alcohol — C16H34O  =  (CHo)i4  occurs   in   the   feather 

i    " 
CH2OH 

glands  of  the  duck  and  forms  an  important  constituent  of  the  wax,  spermaceti, 
obtained  from  a  cavity  in  the  skull  of  the  sperm  whale. 

ALDEHYDES.  By  oxidation  of  any  of  the  alcohols  we  obtain  another 
group  of  compounds — the  aldehj'des.  From  ethyl  alcohol,  for  instance,  by 
warming  with  potassium  bichromate  and  dilute  sulphuric  acid,  ethyl  aldehyde 

is  produced  and  given  off.  In  these  aldehydes  the  group  C^^— H  is  converted  into 
H  1    ^OH 

I 
the  group  C  -=  0,     and  it  is  the  possession  of  this  group  which  determines  the 

I 

aldehyde  character  of  any  compound,  as  well  as  the  reactions  which  are  typical 

of  this  class  of  compounds. 

Some  of  the  tj-pical  reactions  of  aldehj'des  may  be  here  shortly  summarised  : 
(1)  They  act  as  reducing  agents,  the  CHO  group  being  converted  into  the 

group  COOH,  which  is  distinctive  of  an  acid.     We  may  therefore  say  that  on 

oxidation  aldehydes  are  converted  into  the  corresponding  fatty  acids  as  follows  : 

CH3  CH3 

I         +0-1 
CHO  COOH 

(ethyl  aldehyde)  (acetic  acid) 


52  PHYSIOLOGY 

On  account  of  the  ease  with  which  this  oxidation  takes  place,  aldehydes  act  as 
strong  reducing  agents.  Warmed  with  an  alkaline  solution  of  cupric  hydrate, 
they  take  up  oxygen,  reducing  the  cupric  to  a  red  precipitate  of  cuprous 
hydrate.  If  warmed  \\dth  an  ammoniacal  solution  of  silver  {i.e.  silver  nitrate 
solution  to  which  ammonia  has  been  added  mitil  the  precipitate  first  formed 
is  just  redissolved),  they  reduce  the  silver  nitrate  with  the  formation  of  a  mirror 
of  metallic  silver  on  the  surface  of  the  glass  vessel  in  which  they  are  heated. 

(2)  On  warming  with  phenyl  hydrazine,  they  give  the  typical  compounds, 
hydrazones  and  osazones,  which  are  also  given  by  the  sugars  and  will  be 
mentioned  in  connection  with  these  bodies. 

(3)  They  also  form  addition  products.  With  ammonia,  they  yield  the  group 
of  compounds  known  as  aldehyde  ammonia.     Thus  : 


CH3 

CH3 

1     +  NH3 

=   1     /NH2 

CHO 

C— H 

"^OH 

With  sodium  sulphite  the  following  reaction  takes  place  : 

CH3  CH3 

I         +NaHS03=    I      /OH 

CHO  CH<^ 

^S03Na 

These  compounds  of  aldehydes  with  sodium  sulphite  can  be  readily  obtained 
in  a  crystalline  form  and  furnish  a  convenient  means  of  separating  the  alde- 
hydes from  their  solutions. 

(4)  All  the  aldehydes  possess  a  strong  tendency  towards  polymerisation. 
Ethyl  or  acetic  aldehyde  treated  with  strong  sulphuric  acid  gives  the  com- 
pound paraldehyde.     Thus : 

3C2H4O      =        C6H12O3. 

(acetic  aldehyde)        (paraldehyde) 

If  warmed  with  strong  potash  the  polymerisation  occurs  to  a  still  further  extent 
with  the  formation  of  resinous  sixbstances  of  unknown  composition,  but  at 
any  rate  of  a  very  high  molecular  weight,  the  so-called  'aldehyde  resin.'  Formic 
or  methyl  aldehyde,  CH2O,  may  in  the  same  way  imdergo  polymerisation  with 
the  formation  of  a  mixtiue  of  substances  belonging  to  the  group  of  sugars, 
namely,  the  hexoses,  as  follows  : 

6CH2O  =  CeHiaOg. 

This  formation  of  sugar  from  formic  aldehyde  probably  plays  an  important 
part  in  the  assimilation  of  the  carbon  from  the  carbonic  acid  of  the  atmosphere 
by  the  green  parts  of  plants. 

ACIDS.  By  the  oxidation  of  the  group  CHO  of  the  aldehydes  we  obtain 
the  group  COOH,  which  is  characteristic  of  an  organic  acid.  Thus,  formic 
aldehyde  on  oxidation  gives  the  compound  HCOOH,  formic  acid.  Ethyl 
or  acetic  aldehyde,  CH3CHO,  with  an  atom  of  oxygen,  gives  the  compound 
CH3COOH,  acetic  acid. 

CH3  CH3 

I         +0=1 
CHO  COOH. 

Since  these  acids  are  derived  from  the  paraffins  a  whole  series  of  them  exists 


PROXIMATE  CONSTITUENTS  OF  THE  ANIMAL  BODY     5;{ 

corresponding  to  the  series  of  paraffins,  and  known  as  the  fatty  acids.     Examples 
of  this  group  are  : 


F(jrinic  acid 

Acetic  acid 

Pr. 

ipioiiic  acid 

Butyric  acid 

HCOOH 

CH3 

1 

CH3 

CH3 

1 
COOH 

CH2 

COOH 

CH2 

1 
CH2 

COOH. 

In  addition  to   tlieso  fatty  acids,  there  are  also  unsaturated  acids,  derived 
from  the  unsaturated  h\ilrocarboiis. 


DERIVATIVES  OF  THE   FATTY   ACIDS 

AMINO-ACIDS  are  derived  from  the  fattj^  acids  by  the  replacement  of  one 
atom  of  hydrogen  by  tlie  group  XH2. 

Thus  from  propionic  acid  we  may  have  : 


CH,.NHo 


CH, 


CHa 


CH.NHo 


COOH 

ft 


COOH. 


The  second  form,  the  t«-amino  acid,  is  the  onlj^  one  which  occurs  in  the  body. 

OXYACIDS  are  formed  by  the  replacement  of   one  H  atom   by  the  group 
OH.    Thus: 

CH3 

I 
CHOH  is  oxypropionic  acid  or  lactic  acid. 


COOH 

KETO-ACIDS.  Oxyacids  are  formed  by  the  oxidation  of  the  group  CH2 
or  CH3.  If  at  the  same  time  the  H2  group  be  removed  by  oxidation  a  keto- 
acid  may  be  formed.  This  is  probably  the  manner  in  which  such  acids  arise 
in  the  body,  though  it  is  more  usual  to  regard  a  keto-acid  as  the  result  of  oxida- 
tion of  a  ketone.     Thus  : 


CH. 


CH, 


CH, 


CO 


CO 


CO 


CH3 
(acetone) 


CHo.OH 


COOH 

(pyruvic  acid- 
a  keto-acid) 


ACID    AMIDES    are  formed  from  a  fatty  acid  by  replacing  the    -OH    of 
the  -  COOH  group  by  -  NHg,  e.g.  : 


CH, 

I 

CO.NH2 
(acetamide) 


from 


CH, 

I 
COOH. 

(acetic  acid) 


54 


PHYSIOLOGY 


AMINES.  These  may  be  regarded  as  formed  from  ammonia  NHg  by 
replacing  one  or  more  of  the  H  atoms  by  an  organic  radical.  Thus  we  may 
have : 

CH3 
N\CH3 

\h 

( dimethylamine ) 


N( 


CH3 
-H 

(methylamiue) 


/  CHs 

N^CHg 

CH3 

(trimethylamine) 


Under  the  action  of  living  organisms  primary  amines  may  be  formed  from 
«-amino-acids  by  a  process  of  decarboxylation.     Thus  : 


CH. 


CH. 


CH.NH2  -  CO2-  CH2.NH2 

I 
COOH 

(a-amino-propionic  acid)  (ethylamme) 


AROMATIC  COMPOUNDS 

These  all  contain  a  nucleus,  made  up  of  six  carbon  atoms,  which  is  extremely 
stable,  so  that  processes  of  oxidation,  reduction,  &c.,  can  be  carried  out  in  the 
compound  without  destruction  of  the  nucleus.  The  simplest  aromatic  com- 
pound is  benzene  CgHe.  It  behaves  as  a  saturated  compovmd.  It  is  represented 
as  a  hexagon  with  a  hydrogen  atom  at  each  angle. 

H 


H 


H 


H 


H 


H 


All  the  hydrogen  atoms  are  of  equal  value.  They  may  be  replaced  by  other 
groups,  such  as  OH,  CI,  NH2,  or  by  more  complex  groups  belonging  to  the 
fatty  series,  e.g.  CH3,  C2H5,  &c.  Monosubstitution  derivatives  exist  only  in 
one  form : 

CfiHs.X 

Disubstitution  compounds  exist  in  three  forms,  according  to  the  relative 
position  of  the  substituted  H  atoms.  These  are  known  as  the  ortho,  meta, 
and  para  compounds,  and  have  the  formulae  : 


X 


X 


H 


H 


X 


H 


H 


H 


H 


H 


H 


H 


H 


H                            H                            X 

ortho-                       meta-                         para- 

The  following 

are  some  of  the  most  important  monosubstitution  derivatives 

of  benzene  : 

Nitroben  zene                      CgHg .  NOg. 

Aniline                                CgHg.NHa. 

Benzene  svdphonic  acid     CgHg .  SO3H. 

Phenol                                  CeHg.OH. 

Toluene                               C^ils  ■  CH3. 

PROXIMATE  CONSTITUENTS  OF  THE  ANIMAL  BODY    55 


Benzyl  alcohol 
Ben  zy  1  al  dehy  dc 
Benzoic  acid 


CeHg.CHaOH. 

CfiHs.CHO. 

CeHg.COOH. 


Of  the  disubstitution  compounds,  we  need  only  mention  the  following  : 
The  dihydroxi/benzenes : 

Pyrocatechin  or  catechol     Resorcinol  Hydroquinone 


OH 


OH 


OH 


OH 


ortho- 


meta- 


OH 


OH 

paia- 


OH 


Salicylic  acid  (o-hydroxybenzoic  acid)  C8H5< 

Tyrosin  (parahydroxyphenyl  a-alanine) : 

OH 


COOH. 


CH2.CH(NH2)COOH. 
Examples  of  trisubstitution  derivatives  of  benzene  are  : 

OH 


Pyrogallol 

OH 
OH 

OH 

Homogentisic  acid 

OH 

CH2.COOH 

Adrenaline 

OH 

OH 

CH.OH 

CH2.NH(CH5) 

NO2 
Picric  acid 

OH 

/\ 

\/ 
NOj 

NOa 

56 


PHYSIOLOGY 


OPTICAL  ACTIVITY 

Most  of  the  compounds  produced  by  the  agency  of  living  organisms  exhibit 
optical  activity,  i.e.  have  the  property  of  rotating  the  plane  of  polarised  light 
either  to  the  right  or  to  the  left. 

In  an  ordinary  wave  of  light  the  vibrations  of  the  waves  take  place  in  all 
planes  perpendicular  to  the  direction  of  its  propagation.  When  such  a  ray 
is  passed  through  a  Nicol's  prism  (made  of  Iceland  spar)  it  emerges  as  a  plane 
polarised  beam,  i.e.  waves  in  one  plane  only  are  transmitted.  Another  Nicol's 
prism  wll  allow  such  a  ray  to  pass  only  if  it  is  parallel  to  the  first  prism.  If 
it  is  rotated  through  a  right  angle,  no  light  will  pass.  A  Nicol's  prism  may 
thus  be  used  to  determine  the  plane  of  polarisation  of  any  beam  of  light. 

In  the  polarimeter  two  Nicol's  prisms  moimted  parallel  to  one  another 
are  employed.     One  of  them  (the  polariser)  is  fixed  ;  the  other  (the  analj'ser) 


n 


If<    K) 


Sd^OE 


aO  |c  I^B 


i."o 


Fig.  16.     Diagram  of  polarimeter. 
B,  polariser;  D,  analyser;  o,  tube  containing  solution  under  examination. 

can  be  rotated  round  the  axis  of  the  beam  of  light  passing  through  the  first. 
When  both  prisms  are  parallel  light  passes  through  the  analyser.  On  inter- 
posing a  solution^of  an  optically  active  substance  between  the  two  prisms, 
the  plane  of  polarisation  of  the  beam  is  rotated,  so  that  the  light  passing  through 
the  analyser  is  diminished.  The  light  may  be  brought  to  its  original  intensity 
by  rotating  the  analyser  either  to  the  right  (clockwise)  or  to  the  left.  In  this 
way  the  direction  and  degree  of  the  optical  activity  maj^  be  determined.  Optical 
activity  is  connected  with  the  molecular  arrangement  of  the  substance  exhibiting 
this  property,  and  depends  on  the  presence  of  one  or  more  '  asymmetric  carbon 
atoms  '  in  the  molecule. 

CH3  CH3 

!  I 

Thus  in  lactic  acid  H .  COH,  or  in  alanine  HC.NH2,  the  middle  carbon  atom 

I  I 

COOH  COOH 

is  asymmetric,  i.e.  it  is  unequally  loaded  on  the  four  sides. 

We  can  imagine  such  a  carbon  atom  as  occupying  the  interior  of  a  tetra- 
hedron. 

A  B 


Fio.  17, 


PROXIMATE  CONSTITUENTS  OF  THE  ANIMAL  BODY    57 

In  this  tetrahedron,  if  we  represent  the  four  groups  combining  with  the  carbon 
by  Ri,  R2'  ^3'  ^4'  they  can  be  arranged  either  as  in  A  or  B.  It  is  evident 
that  no  amount  of  turning  about  will  convert  the  tetrahedron  A  into  tetra- 
hedron B,  but  that,  if  we  hold  A  before  a  mirror,  its  image  in  the  mirror  will 
be  represented  by  B.  One  arrangement  is  therefore  the  mirror  image  of  the 
other,  and  a  comp<jund  containing  one  such  carbon  atom  will  be  capable  of 
existing  in  two  forms,  namely,  one  form  corresponding  to  A,  the  other  form 
corresponding  to  B.  It  is  foimd  that  the  unequal  loading  of  the  carbon 
atom,  which  is  present  in  such  an  asymmetric  arrangement,  causes  the  com- 
pound containing  the  asymmetric  carbon  to  have  an  action  on  polarised  light. 
One  of  the  varieties  will  rotate  polarised  light  to  the  right,  while  its  mirror 
image  will  rotate  polarised  light  to  the  left.  A  mixture  of  equal  parts  of  the 
two  compounds  will  rotate  equally  to  left  and  right,  i.e.  will  have  no  action 
on  polarised  light. 

The  variety  rotating  to  the  right  is  dextrorotatorj',  and  the  other  Isevo- 
rotatory,  while  the  mixture  of  the  two  is  known  as  the  racemic  or  inactive 
variety.  The  three  forms  are  said  to  he  stereoisomeric,  and  are  distinguished 
as  the  d,  I,  and  i  forms  respectively.  If  two  asymmetric  carbon  atom.«  are 
present  in  a  compound,  we  may  have  four  stereoisomers;  and  generally  if  there 
are  n  asymmetric  atoms  in  a  molecule,  there  will  be  2"  possible  stereoisomers. 
These  will  not  all  be  necessarily  optically  active,  since  the  dextrorotation  due 
to  one  asymmetric  carbon  atom  may  be  exactly  neutralised  by  the  laevorotation 
due  to  another,  so  that  '  internal  compensation  '  takes  place  and  the  substance 
is  optically  inactive.  Thus  in  tartaric  acid  four  forms  are  known,  namely, 
d,  I,  racemic  or  i,  and  mesotartaric,  also  inactive,  in  which  internal  compensa- 
tion occurs.     These  four  varieties  may  be  represented  as  follows  : 


COOH 

COOH 

COOH 

HCOH 

HOCH 

HCOH 

HOCH 

HCOH 

HCOH 

COOH 

COOH 

COOH 

d-tartaric  ; 

icid 

/-tartaric  i 

icid 

mesotartaric  acid 

inactive  tartaric  acid 

Several  methods  may  be  employed  to  separate  the  racemic  form  into  its 
two  optically  active  components.  One  of  these  methods,  first  employed  by 
Pasteur,  is  to  grow  moulds  in  the  solution.  One  of  the  optical  isomers  is 
destroyed,  leaving  the  other  unchanged.  Another  method  is  the  fractional 
crystallisation  of  the  salts  with  alkaloids,  e.g.  strychnine  in  the  case  of  lactic 
acid. 


SECTION   III 

THE  FATS 

These  substances  are  widely  distributed  throughout  the  animal  and 
vegetable  kingdoms.  In  the  higher  animals  they  form  the  main 
constituents  of  the  fatty  or  adipose  tissue  lying  under  the  skin  and 
between  the  muscles  and  often  forming  large  accumulations  around 
the  viscera.  In  the  marrow  of  bones  they  may  amount  to  96  per 
cent.  They  also  occur  in  fine  particles  distributed  through  the 
protoplasm  of  cells  and  probably  also  in  combination  with  the  other 
constituents  which  make  up  protoplasm.  Large  amounts  are  also 
found  in  certain  members  of  the  vegetable  kingdom,  as,  for  instance, 
in  the  fatty  seeds  and  nuts,  e.g.  linseed,  olives,  Brazil  nuts. 


CHEMISTRY  OF  THE   FATS 

The  fats  are  esters  of  glycerol  and  the  fatty  acids.  Glycerol  is  a 
trihydric  or  triatomic  alcohol  and  can  therefore  form  esters  with 
one,  two,  or  three  of  its  hydroxyl  groups ;  thus  with  acetic  acid 
the  following  compounds  are  known  : 


(1) 


CH2OH 


(2) 


CH2OH 


CHOH 


CH— 0— OC.CH, 


CH2O— OC.CH3 

a  -monacet  in 


CH2OH 

/?-monacetin 


monoglycerides 

(3)  (4) 

CH2— 0— OC .  CH3     CH2OH 


(5) 
CH,— 0— OC.CH, 


CHOH 


CH—0— OC.CH, 


CH—0— OC.CH, 


CH2— 0— OC .  CH3     CH2— 0— OC .  CH3 


a,  a  diacetin 


a,  p  diacetin 


diglycerides 


68 


CH2— 0— OC.CH3 

triacetin 
triglyceride 


THE  FATS  59 

In  these  compounds  the  phenomenon  of  isomerism  occurs  owing 
to  the  presence  of  primary  and  secondary  alcohol  groups  in  glycerol. 
In  the  case  of  the  diglycerides  and  the  triglycerides  mixed  esters,  in 
which  the  fatty  acid  radical  varies,  are  possible  : 

(6)  (7) 

CHa-  0— OC .  CHg  CH2OH 

CHOH  OH— O-OC.CH3 

CH2  -0— OC .  CH2 .  CH3  CH2-  0— OC .  CH2CH3 

(8) 
CH2— 0— OC.CH3 

CH— 0— OC.CH2.CH3 

I 
CH2— 0— OC .  CH2 .  CH2 .  CH3 

The  glyceryl  esters  which  compose  the  fatty  material  of  living 
matter- — -whether  animal  or  plant — are  mainly  triglycerides,  the 
monoglycerides  and  diglycerides  being  seldom  found  in  nature.  The 
natural  fat  is  usually  found  to  consist  of  a  mixture  of  triglycerides  ; 
these  triglycerides,  instead  of  being  mixed  esters  as  in  formula  (8),  are 
generally  simple  esters  as  in  formula  (5).  The  differences  in  the  composi- 
tion of  the  natural  fats  depend  therefore  on  the  variety  of  the  fatty 
acid  radical  combined  with  the  glycerol. 

The  fatty  acids  which  enter  into  the  composition  of  the   tri- 
glycerides belong  to  two  main  homologous  series  : 

A.  The  saturated  fatty  acids,  namely  : 
Formic  acid,  H.COOH 
Acetic  acid,  CH3.COOH 
Propionic  acid,  CH3 .  GH2 .  COOH 
Butyric  acid,  CHg.CHa.CHo.COOH 
Valerianic  acid,  CH3.(CH2)3.COOH 
Caproic  acid,  OH3.(CH2)4.COOH 
Capiylic  acid,  CH3 .  (CH2)6  •  COOH 
Capric  acid,  CH3(CH2)8.COOH 
Laurie  acid,  CH3(CHo)io.COOH 
Myristic  acid,  CH3(CH2)i2.COOH 
Palmitic  acid,  CH3(CH2)i.,.COOH 
Stearic  acid,  CH3(CH2),c.COOH 
Arachidic  acid,  CH3(CH2)i8.COOH 
Behenicacid,  CH3(CH2)2o.COOH 
Lignoceric  acid,  CH3(CH2)22  •  COOH 


60"  PHYSIOLOGY 

B.  The  unsaturated  fatty  acids,  namely  : 

(1)  Acrylic  series,  e.(j.  oleic  acid  {Q^^<2.n-2^2) 

(2)  Linoleic  series,  e.g.  linoleic  acid  {QJil^n-i^^i) 

(3)  Linolenic  series,  e.g.  linolenic  acid  (C^H2n_602) 

Of  the  long  list  of  fatty  acids  given  above  only  a  few  occur  to  any 
extent  in  the  animal  body.  In  milk,  although  the  greater  part  of  the 
fat  consists  of  the  triglycerides  of  oleic,  palmitic,  and  stearic  acids, 
other  members  of  the  series  given  above  are  present  in  small  amounts. 
On  the  other  hand,  the  adipose  tissue,  strictly  so  called,  consists  almost 
exclusively  of  the  fats  derived  from  the  fatty  acids  palmitic,  stearic, 
and  oleic,  i.e.  tripalmitin,  tristearin,  and  triolein.  The  great  differences 
in  the  appearance  of  the  fat  of  different  animals  are  due  to  the 
varying  amounts  in  the  relative  quantities  of  these  three  fats  which 
may  be  present.  While  triolein  is  liquid  at  0°  C,  tristearin  and 
tripalmitin  are  solid  at  the  temperature  of  the  body.  According 
to  the  relative  amounts  of  these  three  substances,  therefore,  we 
may  have  a  fat  which,  like  mutton  suet,  is  solid  at  the  body  tem- 
perature, or  a  fat  containing  much  olein  which  is  still  fluid  and  runs 
away  when  the  body  is  opened  after  death,  even  when  it  has  already 
cooled. 

PROPERTIES  OF  THE  FATS.  The  fats  are  colourless  substances 
devoid  of  smell.  They  are  insoluble  in  water,  in  which  they  float. 
They  are  soluble  in  warm  absolute  alcohol,  but  separate  out  into  crystal- 
line form  on  cooling.  They  are  easily  soluble  in  ether.  If  they  are 
strongly  heated  with  potassium  bisulphate  they  give  off  pungent 
vapours  of  acrolein  derived  from  the  decomposition  of  the  glycerin 
of  their  molecule. 

C3H5(OH)3  -  2H.3O  =  C3H,0 

If  they  are  heated  with  water  or  steam  or  submitted  to  the  action  of 
certain  ferments,  they  undergo  hydrolysis,  taking  up  three  molecules 
of  water,  and  are  split  into  three  molecules  of  fatty  acid  and  one 
molecule  of  glycerin,  e.g., 

C3H5(aeH3,02)3  +  3H2O  =  SHCieHaiO^  +  C3H5(OH)3 
(neutral  fat — tripalmitin)       (palmitic  acid)  (glycerin) 

This  process  may  occur  spontaneously  when  fat  is  left  exposed  to 
the  air.  Fat  which  has  thus  been  artificially  split  in  this  way  is  said 
to  be  rancid.  Most  natural  fats  generally  contain  a  small  amount 
of  fatty  acid  which  gives  them  an  acid  reaction. 

On  boiling  a  neutral  fat  for  a  long  time  with  an  aqueous  solution 
of  potassium  or  sodium  hydrate,  or  better  still  with  an  alcoholic 
solution  of  potassium  or  sodium  ethylate,  the  fat  imdergoes  saponifica- 


THE  FATS  61 

tiori;  giving  the  alkaline  salt  of  a  fatty  acid  and  glycerin.  The  former 
compound  is  spoken  of  as  a  soap.  In  water  the  soaps  form  a  sort  of 
pseudo-solution  on  heating  which  sets  to  a  solid  jelly  on  cooling. 
From  a  dilute  watery  solution  the  soap  can  be  thrown  down  in  the 
solid  form  by  the  addition  of  neutral  salts.  Fats  are  insoluble  in 
and  non-miscible  with  water.  If  shaken  up  with  water  the  droplets 
rapidly  run  together  and  rise  to  the  surface,  forming  a  continuous 
layer  of  the  oil  or  fat.  The  same  thing  happens  if  an  absolutely 
neutral  fat  be  shaken  up  with  a  dilute  solution  of  sodium  carbonate. 
If,  however,  the  fat  be  slightly  rancid,  i.e.  if  fatty  acid  be  present, 
the  latter  combines  with  the  alkali  with  the  expulsion  of  CO2  to 
form  a  soap.  The  presence  of  soap  in  colloidal  solution  in  the  water 
at  once  diminishes  or  abohshes  the  surface  tension  between  the 
neutral  fat  and  the  water.  Like  many  other  colloidal  solutions,  a 
soap  solution  presents  the  phenomenon  of  surface  aggregation,  i.e. 
the  concentration  of  the  soap  at  the  surface  is  increased  to  such  an 
extent  as  to  form  practically  a  solid  pellicle  of  molecular  dimensions 
on  the  surface  of  the  fluid.  The  same  peUicle  formation  occurs  at 
the  surface  of  every  oil  globule,  so  that  on  shaking  up  rancid  oil  with 
dilute  sodium  carbonate,  the  whole  of  the  oil  is  broken  up  into  fine 
droplets  which  show  no  tendency  to  run  together  again,  and  remain 
in  suspension  in  the  water.  The  suspension  of  fine  oil  droplets, 
which  has  the  appearance  of  milk,  is  spoken  of  as  an  emulsion. 
It  can  be  at  once  destroyed  by  adding  acid.  This  decomposes  the 
soap,  setting  free  the  fatty  acids,  which  are  insoluble  in  the  water. 
The  pellicle  around  each  globule  is  destroyed,  and  the  globules  run 
together  as  neutral  oil  would  in  pure  water. 

In  order  to  characterise  any  given  animal  fat  or  mixture  of  fats  the  folio-wing 
reactions  are  made  use  of  : 

(1)  Tlie  '  acid  number  '  of  the  fat,  i.e.  its  content  in  free  fatty  acids,  is  deter- 
mined by  titrating  it  in  ethyl  alcohol  solution   with  —     alcoholic  solution  of 

10 
potash,  using  phenolphthalein  as  an  indicator. 

(2)  The  '  saponification  number.'  This  represents  the  number  of  milligrammes 
of  potassium  hydrate  necessary  to  saponify  completely  one  gramme  of  fat. 

(3)  The  percentage  of  volatile  fatty  acids  is  determined  by  saponifying  the 
fat,  then  treating  it  with  a  mineral  acid  to  set  free  the  fatty  acids  and  distilling 
over  the  volatile  acids  in  a  current  of  steam. 

(4)  The  iodine  number  is  the  amount  of  iodine  which  is  taken  uj)  by  a  given 
weight  of  fat.  It  is  a  measure  of  the  amoiuit  of  unsatm-ated  fatty  acid  present, 
i.e.  in  ordinary  fat,  oleic  acid. 

Besides  the  glycerides,  a  certain  number  of  substances  occur  in  the 
body  derived,  not  from  a  combination  of  fatty  acids  with  glycerol, 
but  from  a  formation  of  esters  of  the  fatty  acids  and  other  alcohols, 
e.g.  cholesterol  or  cetyl  alcohol.  Thus,  spermaceti  is  a  mixture  of 
cetyl  palmitate  with  small  quantities  of  other  fats      The  fatty  secre- 


62  PHYSIOLOGY 

tion  of  the  sebaceous  glands  in  man  and  the  higher  animals,  which 
fm:nishes  the  natural  oil  of  hair,  wool,  and  feathers,  consists,  with 
small  traces  of  glycerides.  of  cholesterol  esters.  Lanoline,  which  is 
purified  wool  fat,  consists  almost  entirely  of  cholesteryl  stearate  and 
palmitate.  These  cholesterol  fats  are  attacked  with  extreme  di£&culty 
by  ferments  or  micro-organisms.  It  is  probably  on  this  account  that 
they  are  manufactured  in  the  body  for  protective  purposes.  So 
far  as  we  know,  when  once  formed,  they  are  incapable  of  further 
transformation  in  the  body.  They  are  not  appreciably  altered  by 
the  digestive  ferments  of  the  alimentary  canal,  and  the  cholesterol  is 
said  to  pass  through  the  latter  unaltered.*  Cholesterol  is  also  found 
in  combination  with  fatty  acids  in  every  living  cell.  Whenever 
protoplasmic  structures  are  extracted  with  boiling  ether,  a  certain 
amount  of  cholesterol  is  present  with  the  fats  which  are  so  extracted. 
lu  view  of  the  great  stability  of  this  substance  when  exposed  to  the 
ordinary  mechanisms  of  chemical  change  in  the  body,  it  seems 
probable  that  the  part  played  by  cholesterol  is  that  of  a  framework 
or  skeleton,  in  the  interstices  of  which  the  more  labile  constituents 
of  the  protoplasm  can  undergo  the  constant  cycle  of  changes  which 
make  up  the  phenomena  of  life. 

PHOSPHOLIPINES  OR  PHOSPHATIDES 

The  fats  form  the  chief  constituent  of  the  deposited  and  reserve 
fat  throughout  the  animal  kingdom  and  are  also  contained  in  the 
protoplasm  of  the  living  cell.  The  chief  fatty  constituents  of 
protoplasm  differ  from  the  above  fats  in  the  following  particulars  : 
they  contain  phosphoric  acid  and  an  amine.  On  this  account  they 
have  been  called  phosphorised  fats  Thudichum,  who  isolated  various 
compounds  of  this  nature  from  brain,  suggested  the  term  phospha- 
tides as  a  general  name  for  them.  The  term  lipoid  has  also  been 
used,  but  it  includes  all  the  substances  composing  a  cell  which 
are  soluble  in  ether,  e.g.  cholesterol,  cetyl  alcohol,  and  the  fats. 
Leathes  has  suggested  the  term  phospholipine  for  those  compounds, 
for  it  denotes  that  the  compound  is  partly  fat  (lip),  that  it  contains 
phosphorus,  as  well  as  a  nitrogenous  basic  radical  (ine).  The 
phospholipines  comprise  the  substances  lecithin,  cephaUn,  cuorine, 
sphingomyeline.  In  brain  and  other  tissues  similar  compounds,  which 
contain  no  phosphorus,  occur,  and  in  the  place  of  glycerol  we  may 
find  galactose.  Leathes  has  proposed  calling  these  compounds  lipines 
and  galactolipines. 

Lecithin,  the  chief  phospholipine,  is  an  ester  compounded  of  two 
fatty  acid  radicals  phosphoric  acid,  glycerol,  and  the  amine,  choline. 
The  various  lecithins  may  be  distinguished,  according  as  they  contain 

*  According  to  Gardner,  cholesterol  may  be  absorbed  from  the  intestine. 


THE  FATS  63 

different  fatty  acid  radicals,  as  oleyl-lecithin,  stearyl-lecithin.     The 
following  formula  represents  distearyl-lecithin  : 
CH2-0-OC.(CH2)ieCH3 

I 

CH— 0-OC.(CH,)i6CH3 

>pf 
HO/     ^O.CH2.CH2.N(CH3)3 

I 
OH 

On  warming  with  baryta  water  lecithin  is  broken  down  into  fatt}' 

acid,  glycerophosphoric  acid,  and  choline.     The  latter  base,  which  is 

[C2H4OH 

trimethyl-oxethyl-ammonium  hydrate,  N  -  (CH3)3       must    be     distin- 

[OH 

fC,H3 

guished  from  neurine,  N  -  (CH3)3  which  is  trimethyl- vinyl-ammonium 

[oh 

hydrate,  and  is  much  more  poisonous  than  choline.  Choline  forms  a 
salt  with  hydrochloric  acid,  which,  with  platinum  chloride,  yields  a 
double  salt  of  characteristic  crystalline  form,  insoluble  in  absolute 
alcohol.  The  universal  distribution  of  lecithin  seems  to  indicate 
that  it  plays  an  important  part  in  the  metabolic  processes  of  the 
cell.  There  is  no  doubt  that  it  may  serve,  inter  alia,  as  a  source 
of  the  phosphorus  required  for  building  up  the  complex  nucleo- 
proteins  of  cell  nuclei.  It  seems  to  represent  an  intermediate  stage  in 
the  utilisation  of  neutral  fats  by  protoplasm,  and  its  occurrence  in  the 
brain  as  a  constituent  of  more  complex  molecules,  which  contain  also 
a  carbohydrate  nucleus  (galactosides,  such  as  cerebrin),  might  be  inter- 
preted as  indicating  some  share  also  in  the  metabolism  of  carbohydrates. 
Lecithin  may  be  extracted  from  tissues  by  boihng  with  absolute 
alcohol.  On  cooling  the  alcoholic  extract  in  a  freezing  mixture,  the 
lecithin  separates  out  as  granules  or  semi-crystalline  masses.  When 
dried  in  vacuo,  it  forms  a  waxy  mass,  which  melts  at  40°  to  50°  C.  In 
water  it  swells  up  to  form  a  paste,  which,  mider  the  microscope,  is  seen 
to  consist  of  oily  drops  or  threads,  the  so-called  myelin  droplets.  In 
a  large  excess  of  water  it  forms  an  emulsion  or  a  colloidal  solution. 
Its  power  of  taking  up  water  on  the  one  hand,  and  its  solubihty  in 
alcohol  and  similar  media  on  the  other,  give  it  an  intermediate  position 
between  the  water-soluble  crystalloids  and  the  insoluble  fats,  and 
enable  it  to  play  an  important  part  both  as  a  vehicle  of  nutritive 
substances  and  as  a  constituent  of  the  lipoid  membrane,  which  bounds 
and  determines  the  osmotic  relationships  of  all  living  cells. 


SECTION   IV 

THE    CARBOHYDRATES 

■  The  carbohydrates  are  a  group  of  bodies  of  wide  distribution  and 
great  importance  in  both  the  vegetable  and  animal  kingdoms  In 
plants  the  first  product  of  assimilation  of  carbon  is  a  carbohydrate, 
and  in  animals  these  substances  forin  one  of  the  most  important 
sources  of  energy.  They  consist  of  the  elements  carbon,  hydrogen, 
and  oxygen,  the  two  last-named  being  almost  invariably  in  the  pro- 
portions necessary  to  form  water.  It  is  on  this  account  that  the 
term  carbohydrate  has  been  given  to  the  group.  Their  general  formula 
might  be  expressed  C^Hg^O^.  Certain  derivatives  of  the  group, 
obtained  by  the  substitution  of  methyl  and  other  radicals  for  a 
hydrogen  atom,  though  necessarily  classified  with  carbohydrates  on 
account  of  their  reactions,  do  not  conform  to  this  general  formula,  e.g. 
rhamnose.  CgHigOj.  All  the  carbohydrates  which  are  of  importance 
in  the  animal  economy  contain  six  carbon  atoms  or  a  multiple  of  this 
number.  Analogous  substances,  however,  can  be  prepared  contain- 
ing less  or  more  than  this  number  of  carbon  atoms.  A  series  of 
compounds  exist  which  contain  in  their  molecule  2,  3,  4,  5,  6,  7,  8,  9 
carbon  atoms,  and  are  termed  dioses,  trioses,  tetroses,  pentoses, 
hexoses,  heptoses.  and  so  on  ;  the  termination  '  ose '  with  the 
Greek  numeral  prefixed,  indicating  the  number  of  carbon  atoms,  gives 
them  a  distinct  designation.  These  are  all  oxidation  products  of 
polyatomic  alcohols,  being  either  ketones  or  aldehydes  of  these 
alcohols.  Thus  from  glycerol  we  may  obtain  glyceryl  aldehyde 
COH  '     CH2OH 

CHOH    and   dioxyacetone    CO.      Both   these   substances  behave  as 

CH2OH  CH2OH 

sugars  and  belong    to    the    group    of    trioses.      They  are  generally 

obtained  together   and  are   called  glycerose.     From  the   hexatomic 

CH2OH  COH 

I  I 

alcohol  (CH0H)4  we  may  obtain  either  the    aldehyde  (CH0H)4   or 

I  '  ! 

CH2OH  CH.OH 


THE  CARBOHYDRATES  65 

CH.OH 

CO 

the  ketone  (CH0H)3.     These  two  oxidation  products  of  the  polyatomic 

CH/JH 

alcohols  are  known  as  aldoses  and  ketoses  respectively.  All  these 
compounds  are  distinguished  by  the  termination  '  ose.'  It  is  con- 
venient to  call  those  compounds  containing  six  carbon  atoms  the 
sugars,  because  it  is  to  this  group  that  the  natural  sugars  belong. 

Stereoisomerism  in  the  Swjars.  It  will  be  noticed  that  of  the  six 
carbon  atoms  contained  in  the  sugar  molecule,  e.g.  the  aldose 
CH2OH 

(CH0H)4,  four  are  n-sijimndric,  i.e.  their  four  combining  affinities  are 

COH 

saturated  with  groups  of  different  kinds,  viz.  several  carbon  uiom^.. 
one  H  atom,  and  one  OH  group  : 

C 

H-  C— OH 

I 
C 

They  must  therefore  present  many  stereoisomeric  forms.  If  n  repre- 
sent the  number  of  asymmetric  carbon  atoms  in  a  compound,  the 
possible  number  of  stereoisomers  is  2°.  Thus  an  aldehexose  with  four 
asymmetric  carbon  atoms  (CH0H)4  must  present  2"*  isomers,  i.e.  sixteen 
isomeric  compounds,  so  that  there  nuist  be  sixteen  sugars  all  possessing 
the  formula  CH20H(CH0H)4C0H,  in  addition  to  the  inactive  sugars 
obtained  by  a  mixture  of  two  oppositely  active  members  of  this  group. 
Of  the  sixteen  possible  sugars  of  this  formula,  as  many  as  twelve 
have  been  found  or  have  been  artificially  prepared.  Only  a  small 
number  are,  however,  of  any  physiological  importance.  These  in- 
clude the  aldoses,  glucose,  mannose,  and  galactose,  and  the  ket  so, 
fructose  or  levulose.  All  the  other  sugars  are  unassimilable  by  the 
animal  cell  and  are  not  manufactured  by  plants. 

Since  these  sugars  can  be  divided  into  the  optically  active  and  the 
inactive  varieties,  an  obvious  mode  of  designation  would  be  to  repre- 
sent them  as  d-,  1-.  and  i-  varieties  respectively,  i.e.  dextro-rotatory, 
IjBvo-rotatory,  and  inactive.  On  Fischer's  suggestion,  however,  this 
mode  of  nomenclature  has  been  altered  in  favour  of  representing,  by  the 


66  PHYSIOLOGY 

etter  prefixed,  not  the  optical  qualities  of  the  substance  in  question, 
but  its  relation  to  other  substances,  especially  glucose.  Thus,  d- 
fructose  means  that  fructose  is  the  ketose  corresponding  to  the  dextro- 
rotatory glucose,  d-fructose  itself  being  Isevo-rotatory,  though  its 
active  asymmetric  C  atoms  are  identically  arranged  with  those  in 
glucose.  With  this  limitation  one  may  say  that  it  is  only  the  d-hexoses 
of  a  particular  form  which  are  assimilable,  and  therefore  of  physio- 
logical importance.  The  small  differences  in  the  configuration  of  the 
four  d-sugars  can  be  readily  seen  if  their  graphic  formulae  be  com- 
pared : 

CHO  CHO  CH^OH  CHO 


H.C.OH 

HO.C.H 

CO 

H.C.OH 

HO.C.H 

HO.C.H 

HO.C.H 

HO.C.H 

H.C.OH 

H.C.OH 

H.C.OH 

HO.C.H 

H.C.OH 

H.C.OH 

H.C.OH 

H.C.OH 

CH2OH 

CH^OH 

CH2OH 

CH2OH 

d-glucose 

d-mannose 

d-fructose 

d-galactose 

THE  PENTOSES.     C5H10O5 

These  bodies  occur  largely  in  plants  in  the  form  of  complex  polysaccharides, 
the  pentosanes,  which  give  pentoses  on  hydrolysis  with  acids.  Two  forms 
of  pentose  have  been  found  in  the  animal  body,  namely,  i-arabinose,  which 
has  been  isolated  from  the  \irine  in  cases  of  pentosuria,  and  l-xylose,  which 
occurs  built  up  into  the  nucleic  acid  molecule  of  the  pancreas  and  perhaps 
other  organs.  The  pentoses  can  apparently  be  utilised  by  herbivora  as  food- 
stuffs. We  know  nothing,  however,  as  to  the  part  they  play  in  the  animal  body 
or  as  to  the  causation  of  the  rare  condition  of  pentosuria.  Since,  however,  they 
are  reducing  substances  and  the  presence  of  pentose  in  urine  might  therefore 
lead  to  a  suspicion  of  diabetes,  it  is  necessary  to  mention  the  tests  by  which 
the  presence  of  pentoses  may  be  detected.  The  two  following  are  the  chief 
tests  for  pentoses : 

(1)  The  solution  supposed  to  contain  a  pentose  is  mixed  with  an  equal  volume 
of  concentrated  hydrochloric  acid.  To  the  mixture  is  added  a  small  quantity 
of  solid  orcin  and  the  whole  is  heated.  If  pentose  is  present  the  solution  becomes 
at  first  reddish-blue  and  later  bluish-green.  The  coloiu:  can  be  extracted  on 
shaking  the  iluid  with  amyl  alcohol,  the  solution,  on  spectroscopic  examination, 
showing  an  abi-orption  band  between  C  and  D. 

(2)  Instead  of  adding  orcin,  we  may  add  phloroglucin  to  the  mixture  of 
hydrochloric  acid  and  pentose.  The  solution  on  heating  becomes  first  cherry 
red  and  then  cloudy.  On  shaking  with  amyl  alcohol  a  red  solution  is  obtained 
which  shows  a  band  between  D  and  E. 


THE  CARBOHYDRATES  67 

THE   HEXOSES   AND  THEIR  DERIVATIVES 
The  most  important  of  the  cuibohydiates   belong  to  this  class 
and  are  either  hexoses  or  formed  by  a  combination  of  two  or  more 
hexose  molecules.     They  are  divided  into  three  main  groups  : 

(1)  Monosaccharides,  with  the  formula  CgHiaOg,  examples  of 
which  are  glucose,  fructose,  &c. 

(2)  Disaccharides,  which  are  derived  from  two  molecules  of  a  mono- 
saccharide with  the  elimination  of  a  molecule  of  water,  as  follows  : 
2C6Hi206  —  HoO  =  CiaH^aOii-     (Examples,  maltose  and  cane  sugar.) 

(3)  Polysaccharides,  composed  of  three  or  more  molecules  of  a  mono- 
saccharide. The  number  of  molecules  which  are  associated  in  the 
compounds  of  this  gioup  may  be  very  large.  We  can  regard  their 
general  formation  as  represented  by  the  following  equation  : 

nCeHi^Oe  -  nH,0  =  (CsHioO^),. 

(Examples,  starch,  dextrin,  &c.) 

THE  MONOSACCHARIDES 

Only  four  hexoses  out  of  the  large  number  which  have  been 
synthetised  are  assimilable  by  the  animal  body.  These  are  mannose, 
glucose,  galactose,  and  fructose,  the  three  former  being  aldoses,  while 
the  last  is  a  ketose.  All  of  them  are  derivatives  of  d-glucose.  They 
may  be  synthetised  in  several  ways.  The  most  interesting,  because  it 
probably  represents  the  mechanism  of  synthesis  of  hexoses  in  plants, 
is  the  formation  from  formaldehyde.  In  alkaline  solutions  formalde- 
hyde polymerises  with  the  formation  of  a  mixtm-e  of  hexoses  knoN\ni 
as  acrose.  From  this  mixtm'e  a-acrose  can  be  isolated  by  the  forma- 
tion of  its  osazone  and  the  reconversion  of  this  osazone  into  sugar. 
It  is  found  to  be  identical  with  i-fructose.  If  a  solution  of  this 
i-fructose  be  treated  with  yeast,  d-fructose  is  fermented,  leaving 
1-fructose  behind.  For  the  preparation  of  d-fructose  it  is  necessary 
to  convert  the  inactive  sugar  into  the  corresponding  acid,  mannonic 
acid.  This  with  strychnine  or  morphia  forms  salts  which  can  be 
separated  into  the  d-  and  1-  groups  by  fractional  crystallisation.  From 
the  d-  modification  d-mannose  can  be  obtained,  and  this  by  conversion 
into  the  osazone  and  reconversion  into  a  sugar  gives  d-fructose. 

All  the  monosaccharides,  however  many  carbon  atoms  they 
contain,  present  certain  general  reactions  determined  by  their 
chemical  composition. 

((/)  Like  ordinary  aldehydes  and  ketones,  the  sugars  act  as  strongly 
reducing  substances,  and,  like  aldoliydes.  reduce  ammoniacai  solution 
of  silver  to  metallic  silver,  and  many  of  the  higher  u.xides  of  metals 


68  PHYSIOLOGY 

to  lower  oxides.  On  this  behaviour  is  founded  the  commonest  of  all 
the  tests  for  the  presence  of  reducing  sugar^ — -Trommer's  test. 

(6)  On  oxydising  a  monosaccharide  the  COH  group  becomes  con- 
verted to  COOH.     Thus,  glucose  on  oxidation  gives  gluconic  acid  : 

COH(CHOH)4CH20H  +  0  =  COOH(CHOH)4CH20H. 

On  further  oxidation  the  end  group  CHgOH  also  is  affected,  and  we 
obtain  a  dibasic  acid.     Thus  glucose  gives  saccharic  acid. 

(c)  By  means  of  nascent  hydrogen  the  monosaccharides  can  be 
reduced  to  the  corresponding  polyatomic  alcohol.  Thus  the  three 
hexoses,  glucose,  fructose,  and  galactose,  give  the  corresponding  three 
alcohols,  sorbite,  mannite,  and  dulcite  C6H14O6. 

(d)  Anothsr  important  general  reaction  of  the  monosaccharides 
depending  on  the  COH  or  the  CO  group  is  the  reaction  with  phenyl 
hydrazine.  On  warming  a  solution  of  sugar  with  a  solution  of  phenyl 
hydrazine  in  acetic  acid,  the  following  reactions  take  place.  The  first 
reaction  results  in  the  production  of  a  hydrazone  : 

CH20H(CHOH)3CHOHCHO  +  HaN.NH.CeH^  = 
CHoOH(CHOH)3CHOH.CH  :  N  :  NH.CeHs  +  H,0. 

The  hydrazone  then  reacts  with  another  molecule  of  phenyl  hydrazine 
with  the  production  of  an  osazone  : 

CH2(OH)(CHOH)3CHOH.CH  :  N.NH.CeHj  +  HgN.NHCgHs  = 
CH20H(CHOH)3C .  CHN .  NH .  CgHs 

II 

N.NH.CoH^  +  H^O  +  H^. 

The  hydrogen  formed  in  this  reaction  acts  upon  a  second  molecule  of 
phenyl  hydrazine,  splitting  it  into  aniline  and  ammonia.  On  this 
account  it  is  always  necessary  to  have  an  excess  of  phenyl  hydrazine  in 
the  operation. 

The  osazones  form  well-defined  crystalline  products  which  are 
generally  yellowish  in  colour  and  differ  in  their  melting-point  and  in 
their  crystalline  form.  They  are  therefore  of  extreme  value  in  the 
separation  and  identification  of  different  carbohydrates.  They  can 
be  also  used  for  the  artificial  preparation  of  certain  sugars.  Under 
the  influence  of  acetic  acid  and  zinc  dust  they  form  osamines,  which  on 
treatment  with  nitrous  acid  are  reconverted  into  the  corresponding 
sugar,  generally  a  ketose. 

GLUCOSE,  DEXTROSE  or  GRAPE  SUGAR,  is  the  chief  con- 
stituent of  the  sugar  of  fruits,  especially  of  grapes.  It  occurs  in  the 
body  as  the  end-product  of  the  digestion  of  starch.  When  pure  it 
forms  white  crystals  which  melt  at  100°  C,  and  lose  the  one  molecule 
of  water  of  crystallisation  at  110'^  0.     It  is  easily  soluble  in  water  and 


THE  CARBOHYDRATES  69 

the  solution  shows  J)i-i'otation.     Its  final  specific  rotatory  power  at 
20°  C.  is  52-74. 

TESTS  FOR  GLUCOSE.  Trommer's  test  dcpencls  on  the  iiower  possessed  in 
common  ^sith  tlic  other  sugars  of  reducing  cupric  hydrate  to  cuprous  oxide. 
The  sugar  solution  is  made  alkaline  willi  caustic  potash  or  soda,  and  a  few  drops 
of  copper  sulphate  solution  added.  On  heating  the  hlue  solution  thus  obtained 
to  boiling,  it  turns  yellow,  and  a  yellowish-red  precipitate  of  cuprous  hydrato 
is  produced.  This  test  is  generally  performed  wth  Fehling's  solution,  which 
consists  of  an  alkaline  solution  of  cupric  hydrate  in  Rochellc  salt.  The  propor- 
tions in  making  the  solutions  are  so  arranged  that  10  c.c.  of  Fehling's  solution 
are  completely  reduced  by  'Oo  gramme  glucose.  This  reaction  is  made  use  of 
iov  the  quantitative  determination  of  glucose  in  solution.  The  determination 
may  be  carried  out  either  volumetrically,  as  in  Fehling's  or  Pavy's  method,  or 
gra\'i metrically,  as  in  Allihn's  method. 

Moore's  Test.  A  solution  of  glucose  treated  Avith  a  little  strong  caustic  potash 
or  soda  and  warmed,  becomes  first  yelloAV  and  then  gradually  dark  brown,  and 
gives  olf  a  smell  of  caramel. 

With  ordinary  yeast,  glucose  solutions  ferment  readily,  giving  off  COo,and 
form  alcohol  with  small  traces  of  amyl  alcohol,  glycerin,  and  succinic  acid. 

With  phenj'l  hydrazine  glucose  gives  well-marked  needles  of  glucosazone. 
These  are  precipitated  when  the  liquid  is  still  hot,  the  precipitate  being  increased 
as  the  liquid  cools.  The  crystals  form  bundles  of  fine  yellow  needles  which  are 
almost  insoluble  in  water,  but  are  soluble  in  boiling  alcohol.  When  purified  by 
recrystallisation  they  melt  at  204-205°  C. 

On  treating  a  watery  solution  of  glucose  with  benzoyl  chloride  and  caustic 
soda  and  shaking  till  the  smell  of  benzoyl  cldoride  has  disappeared,  an  insoluble 
precipitate  is  produced  of  the  benzoic  ester  of  glucose.  This  method  has  been 
often  used  for  isolating  glucose  from  fluids  in  which  it  occurs  in  minute  quantities. 

Molisch's  Test.  On  treating  O'Sc.c.  of  dilute  glucose  solution  with  one  drop 
of  a  10  per  cent,  alcoholic  solution  of  a-naphthol,  and  then  pouring  1  c.c.  of 
concentrated  sulphuric  acid  gradually  down  the  side  of  the  tube,  a  purple  ring 
is  produced  at  the  junction  of  the  two  fluids,  which  on  shaking  spreads  over  the 
whole  fluid.     This  reaction  depends  on  the  formation  of  furfurol  from  the  glucose. 

In  order  to  identify  glucose  in  a  normal  fluid,  the  following  tests  may  bo 
ai^plied,  after  removing  any  protein  which  may  be  present  : 

(1)  Reduction  of  cupric  hydrate  or  Fehling's  solution. 

(2)  Estimation  of  reducing  power  of  solution. 

(3)  Estimation  of  rotatory  power  of  solution  on  polarised  light. 

(4)  Formation  of  osazone  crystals  with  phenyl  hydrazine.  These  crystals 
must  come  down  while  the  fluid  is  still  hot.  They  must  be  purified  and  their 
melting-point  taken.  A  determination  by  combustion  of  their  nitrogen  content 
will  give  direct  information  whether  the  sugar  is  a  monosaccharide  or  disaccharide. 

(o)  The  solution  is  made  acid  and  boiled  for  some  time.  It  is  then  made 
up  to  its  former  volume  and  its  reducing  power  and  efi'ect  on  polarised  light  once 
more  taken.  In  the  case  of  a  disacciiaride,  which  would  be  converted  into  mono- 
saccharide by  boiling  in  acid  solution,  these  two  readings  would  be  altered, wliereas 
neither  the  rotatorj-  power  nor  the  reducing  power  of  glucose  would  undergo 
any  change. 

(6)  Fermentation  with  ordinary  yeast. 

A  positive  residt  would  exclude  glycuronic  acid. 

D-FRUCTOSE,  or  LEVULOSE,  occurs  mixed  with  dextrose  in 
honey  and  in  fruit  sugar.      It  is  also,  with  glucose,  formed  by  the 


70  PHYSIOLOGY 

digestion  or  inversion  of  cane  sugar.  It  is  difficultly  crystallisable. 
Its  watery  solution  is  Isevo-rotatory,  and  reduces  Fehling's  solution 
somewhat  less  strongly  than  glucose,  its  reducing  power  being  92, 
if  we  take  that  of  glucose  as  100.  It  ferments  readily  with  yeast ; 
with  phenyl  hydrazine  it  gives  the  same  osazone  as  is  formed  from 
glucose. 

GALACTOSE  is  formed  by  the  digestion  or  hydrolysis  of  milk 
sugar  or  lactose.  It  is  also  obtained  on  hydrolysing  cerebrin,  a  con- 
stituent of  the  brain,  with  dilute  mineral  acids,  and  by  the  hydrolysis 
of  certain  vegetable  gums.  It  is  much  less  soluble  in  water 
than  glucose.  It  is  dextro-rotatory  and  shows  marked  bi-rotation. 
With  ordinary  yeast  it  ferments  but  extremely  slowly.  One  species 
of  yeast  is  known,  namely,  saccharomyces  apiculatus,  which,  while 
fermenting  d-fructose  and  glucose,  has  no  effect  on  galactose.  This 
yeast  can  therefore  be  used  to  isolate  galactose  from  a  mixture  of  the 
monosaccharides.  It  reduces  Fehling's  solution,  its  reducing  power 
being  somewhat  less  than  that  of  glucose.  Yeasts  can  be  trained  to 
ferment  galactose. 

MANNOSE,  Mannose,  though  an  assimilable  sugar,  is  of  such  rare  occur- 
rence in  our  food-stuffs  that  it  plays  practically  no  part  in  animal  physiology. 
It  is  dextro-rotatorj%  reduces  Fehling's  solution,  ferments  easUy  -nith  ordinary 
yeast,  and  gives  an  osazone  which  is  identical  with  that  derived  from  glucose. 

DERIVATIVES  OF  THE   HEXOSES 

Two     derivatives    of     glucose    are    of    considerable    physiological 
importance,  namely,  glucosamine  and  glycuronic  acid. 
Glucosamine,  CeHjgNOj,  has  the  structural  formula  : 

CH2OH 

(CH.0H)3 

CH.NH, 

CHO 

It  is  obtained  from  chitin,  which  forms  the  exoskeleton  of  large 
numbers  of  the  invertebrata,  by  boiling  this  with  concentrated  hydro- 
chloric acid.  It  is  stated  to  have  been  obtained  as  a  decomposi- 
tion product  of  certain  proteins  and  their  derivatives,  such  as  the 
mucins.  It  is  of  special  interest  as  affording  an  intermediate  product 
between  the  carbohydrates  and  the  oxy-amino  acids  which  can  be 
obtained  by  the  disintegration  of  proteins.     In  solution  it  is  dextro- 


.    THE  CARBOHYDRATES  71 

rotatory,  reduces  Fehling's  solution,  and  gives  an  osazone  resembling 
that  derived  from  glucose. 

GLYCURONIC  ACID,  C^Hif^O^,  may  be  regarded  as  one  of  the 
first  results  of  oxidation  of  the  glucose  molecule.  The  group 
which  has  undergone  oxidation  is  not  the  readily  oxidisable  CHO 
group,  but  the  CH2OH  group  at  the  other  end  of  the  molecuh.  The 
formula  of  this  acid  is  therefore  : 

COOH 

(CH.0H)4 

I 
CHO. 

In  the  free  state  it  does  not  occur  in  the  animal  body.  It  is 
constantly  found  in  the  urine  after  administration  of  certain  drugs 
such  as  phenol,  camphor,  or  chloral,  and  then  occurs  as  a  conjugated 
acid  with  these  substances.  These  conjugated  acids  are  laevo- 
rotatory,  though  the  free  acid  is  dextro-rotatory.  In  the  free  state 
it  reduces  Fehling's  solution  and  gives  an  osazone  which  is  not 
sufficiently  characteristic  to  distinguish  from  glucosazone.  It  does 
not  undergo  fermentation  with  yeast.  This  test  is  therefore  the 
best  means  of  distinguishing  the  acid  in  urine  from  glucose. 

THE  FORMATION  OF  GLUCOSIDES 
The  graphic  formulae  given  on  p.  66  do  not  explain  all  the 
possible  modes  of  arrangement  of  the  groups  of  the  sugar  molecules. 
Many  of  these  sugars,  when  dissolved  in  water,  present  the  phenomenon 
known  as  multi-rotation.  If  their  rotatory  power  be  taken  immediately 
aftsr  solution,  it  is  found  to  be  greater  or  less  than  the  rotatory  power 
taken  some  hom-s  or  days  later.  Glucose,  for  instance,  immediately 
after  solution,  has  a  high  specific  rotatory  power,  which  diminishes 
rapidly  if  the  solution  be  boiled,  and  more  slowly  if  it  be  allowed  to 
stand.  Finally,  the  specific  rotatory  power  becomes  constant  at 
-f  53°  D.  This  change  in  rotatory  power  seems  to  be  associated 
with  a  change  in  the  arrangement  of  the  groups,  the  aldose,  for  example, 
assuming,  by  the  shifting  of  a  mobile  oxygen  atom,  what  is  known  as  a 
lactone  arrangement. 

Thus  glucose  C0H(CH0H).,CH0H.CTI0H.CH20H  beomes 
CHOH .  (CH0H)2 .  CH .  CHOH .  CH2OH 


0 

This  change  in  the  arrangement  of  the  mo]eeiiIi>  r«'nr].'T>  n   further 


rl 


PHYSIOLOGY 


stereoisomerism  possible,  owing  to  the  fact  that  now  the  end   group 
which  was  formerly  COH  becomes 

H 
0— C— OH 


C 

so  that  now  there  are  five  instead  of  fom-  asymmetric  carbon  atoms. 
The  two  isomers  of  glucose,  which  are  thus  rendered  possible,  are 
represented  by  the  following  structural  formula)  : 

H— C\— OH  OH-a-H 


or 


HCOH 


HCOH 


CH.,OH 


CH.,OH 


In  these  molecules  the  OH  attached  to  the  end  group  can  be  replaced 
by  other  radicals,  including  other  sugar  molecules.  In  this  way  we 
get  the  formation  of  glucosides.  Thus,  if  glucose  be  dissolved  in 
methyl  alcohol  and  be  treated  with  hydrochloric  acid,  we  obtain  a 
and  (3  methyl  glucosides.  the  formulte  of  which  would  be  represented 
as  follows  : 

-C- 


H— C^— OCH 


CH3O 


HCOH 


HCOH 


CH,OH 


CH,OH 


Instead  of  methyl  we  might  insert  other  groups,  and  even  other  hexose 
groups,  such  as  glucose  or  galactose,  obtaining  the  two  sugars  maltose 
and  lactose,  which  may  thus  be  regarded  as  glucosides — maltose  as  the 


THE  CARBOHYDRATES 


73 


a  glucoside  of  ulueose,  lactose  as  the  ft  galactoside  of  glucose.  The 
mode  of  combination  of  the  two  hexose  groups  to  form  these  disac- 
charidcs  may  be  lepresented  as  follows  : 


CH2OH 


H 
—  C 
OH 


H  OH     H    H 
-  C  —  C  —  C  —  C  glucose  rest 
H  OH 


HO     H  HO   HO 

OHO— C  — C  — C— C 
H  OH     H     H 


■  CHo  I'hicose  rest 


iltose. 


H       /OH    H 

CH,OH-C--C  — C— C 

OH     H     H  OH 


HO      H  HO  HO 

OHO  — 0— C  — C  — C 
H  OH     H     H 


C    aalactose  rest 


0 


CH2  glucose  rest 


lactose. 


A  very  large  number  of  glucosides  occur  as  plant  products.     Among 
these  we  may  mention  amygdalin,  salicin,  phloridzin,  indican,  &c. 


THE  DISACCHARIDES 

Tlie  disaccharides  are  formed  by  the  union  of  two  molecules  of 
monosaccharides  with  the  elimination  of  one  molecule  of  water,  and 
can  be  regarded,  according  to  the  manner  in  which  the  molecules 
are  combined,  as  glucosides,  galactosides,  &c.  On  hydrolysis,  e.g. 
on  heating  with  acids,  they  take  up  one  molecule  of  water  and  are  split 
up  into  the  corresponding  monosaccharides.  Thus,  cane  sugar  gives 
equal  parts  of  glucose  and  fructose,  maltose  gives  equal  parts  of  glucose 
and  glucose,  while  milk  sugar  or  lactose  gives  equal  parts  of  glucose 
and  galactose. 

CANE  SUGAR,  sometimes  known  as  saccharose,  is  widely  dis- 
tributed throughout  the  vegetable  kingdom,  and  forms  an  imj>ortaiit 
article  of  diet.  It  has  no  reducing  power  on  Fehliiig's  solution.  It  is 
strongly  dextro-rotatory  and  has  a  specific  rotatory  power  of  -j-  60-5''. 
On  hydrolysis  it  is  converted  into  equal  molecules  of  glucose  and 


74  PHYSIOLOGY 

fructose.  Owing  to  the  fact  that  fructose  rotates  polarised  light 
more  strongly  to  the  left  than  glucose  does  to  the  right,  the  mixture 
of  the  two  monosaccharides  so  obtained  is  Isevo-rotatory.  On  this 
account  the  change  from  free  cane  sugar  to  the  mixture  of  mono- 
saccharides is  know)i  as  inversion,  and  the  mixture  is  often  spoken 
of  as  '  invert  sugar.'  The  term  '  inversion  '  has  since  been  loosely 
applied  to  the  process  of  hydrolysis  itself,  so  that  we  often  speak  of 
the  inversion  of  maltose  or  of  lactose,  meaning  thereby  the  hydrolysis 
of  these  sugars  with  the  production  of  their  constituent  monosac- 
charides. With  yeast,  cane  sugar  first  undergoes  inversion  by  a  special 
ferment  present  in  the  yeast  {invertase),  and  the  mixture  of  fructose 
and  glucose  is  then  fermented. 

MALTOSE  is  formed  during  the  hydrolysis  of  starch  by  acids 
or  by  digestive  ferments,  and  is  also  the  chief  sugar  in  germinating 
barley  or  malt.  It  is  strongly  dextro-rotatory,  ferments  easily  with 
yeast,  and  reduces  Fehling's  solution  ;  its  reducing  power  is  about 
70  per  cent,  of  that  of  glucose.  With  phenyl  hydrazine  it  gives 
phenyl  maltosazone,  which  forms  definite  yellow  crystals  with  a 
melting-point  of  260°  C. 

MILK  SUGAR  or  LACTOSE  is  found  only  as  a  constituent  of  milk. 
It  forms  colourless  rod-like  crystals,  which  are  much  less  soluble  in 
water  than  are  the  two  other  disaccharides.  On  account  of  this 
solubility  it  is  much  less  sweet  than  either  cane  sugar  or  maltose.  It 
is  dextro-rotatory  and  shows  bi-rotation.  It  is  not  fermented  by 
ordinary  yeast.  Before  fermentation  can  occur  the  lactose  must  be 
split  by  the  agency  of  acids  or  by  a  ferment,  lactase,  which  occurs  in 
the  animal  body  and  in  certain  moulds,  into  the  monosaccharides  glucose 
and  galactose.  Lactose  reduces  Fehling's  solution  and  gives  with 
phenyl  hydrazine  lactosazone,  which  is  easily  soluble  in  hot  water 
and  therefore  does  not  come  down  until  the  fluid  is  cold. 

THE  POLYSACCHARIDES 

These  play  an  important  part  throughout  the  whole  vegetable 
kingdom,  where  all  the  supporting  tissues  of  the  plants,  their  protec- 
tive substances,  and  many  of  their  reserve  materials  consist  of  members 
of  this  group.  In  the  animal  body,  where  the  supporting  tissues  are 
composed  chiefly  of  derivatives  of  proteins,  the  sole  significance  of 
polysaccharides  lies  in  their  value  as  food-stuifs.  In  plants,  anhydrides 
both  of  hexoses  and  pentoses  occur  in  bewildering  variety.  Here, 
however,  we  may  confine  our  attention  to  those  members  of  the  group 
of  polysaccharides  which  are  important  as  food-stuffs. 

STARCH  (CgHioOs)  is  present  in  large  quantities  in  nearly  all 
vegetable  foods,  and  is  an  important  constituent  of  the  cereals, 
from  which  flour  and  bread  are  derived,  as  well  as  of  tubers,  such  as  the 


THE  CARBOHYDRATES  75 

potato.  In  the  plant  cells  it  occurs  as  concentrically  striated  grains 
within  minute  protoplasmic  structures — the  amyloplasts,  the  office 
of  which  it  is  to  manufacture  starch  from  the  f^lucose  present  in  the 
cell  sap.  When  freed,  by  breaking  up  the  cells  and  washing  with 
water,  it  forms  a  white  powder  consisting  of  microscopic  grains,  each 
of  which  presents  the  characteristic  concentric  striation.  It  is  in- 
soluble in  cold  water.  In  hot  water  the  grains  swell  up  and  burst, 
forming  a  thick  paste,  which  sets  to  a  jelly  on  cooling.  This  semi- 
solution,  as  well  as  the  original  starch-grains,  gives  an  intense  blue 
colour  on  the  addition  of  iodine.  On  treating  starch  with  cold  alkahes 
or  cold  dilute  acid,  it  is  converted  into  a  soluble  modification,  the 
so-called  soluble  starch  or  amylodextrin,  which  also  gives  a  blue 
colour  with  iodine.  This  modification  is  also  produced  as  the  first 
stage  of  the  action  of  diastatic  ferments  upon  starch.  On  boiling 
with  dilute  acids,  starch  is  converted  first  into  a  mixture  of  dextrins, 
then  into  maltose,  and  finally  into  glucose.  On  acting  upon  starch 
with  various  ferments,  such  as  the  diastase  which  may  be  extracted 
from  malt  or  germinating  barley,  or  with  the  amylase  occurring  in 
saliva  or  pancreatic  juice,  it  undergoes  hydrolysis,  the  final  result  of 
the  action  being  a  mixture  of  four  parts  of  maltose  to  one  part  of 
dextrin.  As  to  the  intermediate  stages  in  this  reaction  opinions 
are  still  divided.  The  first  product  is  soluble  starch,  amylodextrin, 
giving  a  blue  colour  with  iodine.  This  breafe  up  into  a  reducing 
sugar,  and  another  dextrin,  erythrodextrin,  which  gives  a  red  colour 
with  iodine,  and  this  dextrin,  on  fm-ther  hydrolysis,  yields  reducing 
sugar  and  achroodextrin,  which  is  not  coloured  by  the  addition  of 
iodine.  Thus  there  are  a  series  of  successive  hydrolytic  decomposi- 
tions of  the  molecule,  each  resulting  in  the  sphtting  off  of  a  molecule 
of  sugar  and  the  production  of  a  lower  dextrin. 

The  DEXTRINS  are  ill-defined  bodies  which  are  difficult  to  separate. 
They  are  amorphous  white  powders,  easily  soluble  in  water,  forming 
solutions  which,  when  concentrated,  are  thick  and  adhesive.  They 
are  insoluble  in  alcohol  and  ether.  With  cupric  hydrate  and  caustic 
alkali  they  form  blue  solutions,  which  reduce  slightly  on  boiling. 
They  are  not  precipitated  by  saturation  with  ammonium  sulphate. 
On  boiling  with  dilute  acids,  they  are  converted  entirely  into  glucose, 

Tlip  changes  undorgono  by  starch  during  its  hj'^drolysis  by  means  of  diastase 
liavo  been  used  by  Brbwii  and  his  co-workers  as  a  method  of  arri\'ing  at  .some 
idea  of  the  size  and  structure  of  the  starch  molecule.  Proceeding  from  the 
discovery  that  the  end-products  of  this  reaction  consisted  of  81  per  cent,  maltose 
and  in  per  cent,  dextrin,  they  concluded  tliat  starch  must  consist  of  fivedextriii- 
like  groups,  four  of  which  are  arranged  synimctrically  round  tlie  lifth.  At 
eacli  stage  one  of  tlu'se  gi'oups  is  split  olT  and  hydrolyscd  to  form  malto-dextrin  : 

!/.-!'■  tl'"''J^'\  1    tJ'!'-'  molecule  of    water    being    takeji  up.     The  malto-dextrin 

U^12«-20^10)2i 


76  PHYSIOLOGY 

group  is  then  changed  into  maltose  by  the  further  assimilation  of  two  molecules 
of  water.  The  central  dextrin-like  group  is  attacked  with  great  difficulty 
by  the  ferment,  and  therefore  remains  at  the  end  of  the  reaction  as  achroo- 
dextrin.  The  malto -dextrin,  the  penultimate  stage  in  the  action  of  diastase, 
can  be  regarded  as  formed  by  the  condensation  of  tlu-ee  molecules  of  maltose 
attached  by  the  oxygen  of  two  CHO  groups,  so  that  one  CHO  group  remains 
free  and  determines  the  reducing  power  of  the  malto-dextrin  molecule.  Its 
formula  may  therefore  be  represented  as  follows  : 

/C12H21O10 

/C12H20O9 
0< 

Ql2H2iOio\ 

the  sign  -'    being  used  to  denote  the  open  teruiinal  CHO  group. 

They  further  found  that  the  stable  dextrin  remaining  at  the  end  of  the 
diastatic  hydrolysis  of  starch  probably  had  the  formula  of  4OC6H10O5H0O,  and 
might  be  regarded  as  a  condensation  of  forty  glucose  molecules  with  the  elimi- 
nation of  thirty-nine  molecules  of  water.  The  starch  molecule  cannot  be  less 
than  five  times  that  of  the  stable  achroodextrin.  Since  the  latter  has  a  molecular 
weight  of  6498,  the  molecular  weight  of  starch  cannot  be  less  than  32,400,  and 
its  emphical  formula  can  be  represented  bj' : 

IOOC12H20O10,  or  (8OC12H20O10.4OC6H10O5). 

INULIN.  Another  kind  of  starch,  known  as  inulin,  occurs  in  dahlia 
tubers.  It  is  easily  hydrolysed  by  weak  acids,  and  is  entirely  con- 
verted into  d-fructose,  or  leviilose. 

GLYCOGEN,  or  animal  starch,  is  found  in  the  liver,  muscles,  and 
other  tissues  of  the  body,  and  occurs  in  large  quantities  in  all  foetal 
tissues.  It  is  a  white  powder,  soluble  in  water,  forming  an  opalescent 
solution.  It  is  precipitated  from  its  solution  on  the  addition  of 
alcohol  to  GO  per  cent.,  or  by  saturation  with  solid  ammonium  sul- 
phate. On  boiling  wuth  acids,  it  is  entirely  converted  into  glucose.  It 
is  affected  by  the  ferments  diastase  and  amylase,  in  the  same  way  as 
vegetable  starch,  giving  first  dextrins  and  finally  a  mixture  of  maltose 
and  dextrin.  With  iodine  it  gives  a  mahogany-red  colour,  which,  like 
the  blue  colour  produced  in  starch,  is  destroyed  by  boiling,  to  return 
again  on  cooling.  We  shall  have  occasion  to  consider  its  properties 
more  fully  when  we  are  dealing  with  the  functions  of  the  liver. 

THE  CELLULOSES.  Cellulose  (CeHioOg)^  is  a  colourless,  in- 
soluble material,  or  mixture  of  materials,  which  compose  the  cell  walls 
of  the  younger  parts  of  plants,  and  therefore  forms  a  constituent  of 
most  of  our  vegetable  foods.  It  is  insoluble  in  water  or  dilute  acids 
or  alkalies,  its  only  solvent  being  an  ammoniacal  cupric  oxide  solution. 
On  boiling  with  strong  acids,  it  gradually  undergoes  hydroh'sis  and 
yields  sugar,  the  nature  of  which  varies  according  to  the  source  of  the 
cellulose.      In    herbivorous    animals    cellulose    undergoes    digestive 


THE  CARBOHYDRATES  77 

changes  and  forms  an  important  constituent  of  their  food.  The  solu- 
tion of  the  celhilose  in  this  case  is  effected  by  the  agency,  not  of  fer- 
ments secreted  by  the  wall  of  the  gut,  but  of  micro-organisms  which 
swarm  in  the  paunch  of  ruminants  and  in  the  ccecum  of  other  herbi- 
vora.  In  some  cases  the  effective  agent  is  a  cytase  present  in  the 
vegetable  cells  themselves.  Since  this  ferment  is  destroyed  by 
boiling,  cooked  hay  is  much  less  digestible  than  in  the  raw  condition. 
In  certain  invertebrata  it  seems  probable  that  a  true  cellulose-digesting 
ferment,  or  cytase,  is  secreted  by  the  walls  of  the  alimentary  canal. 
In  man  cellulose  undergoes  practically  no  change  in  digestion,  and 
serves  merely  by  its  bulk  to  promote  peristalsis  and  the  normal 
evacuation  of  the  bowels.  A  further  consideration  of  its  chemical 
properties,  as  well  as  of  the  closely  allied  vegetable  materials,  gums, 
pectins,  mucilages,  derived  for  the  most  part  from  the  condensation  of 
pentose  molecules,  may  be  dispensed  with  here. 


SECTION   V 
THE  PROTEINS 

As  sources  of  energy  to  the  organism  all  three  classes  of  food-stuffs 
are  valuable  in  proj)ortion  to  their  heat  ecjuivalents,  and  it  is  often  a 
matter  of  indifference  whether  the  main  bulk  of  the  energy  requii'ed 
is  supplied  at  the  expense  of  fat  or  at  the  expense  ot  carbohydrate. 
The  proteins,  however,  form  the  most  important  constituent  of  living 
protoplasm.  On  this  account  protein  must  always  be  present  in 
the  food  to  supply  the  material  necessary  for  building  up  new  protoplasm 
in  the  growing  animal  and  for  replacing  the  waste  of  living  material 
which  is  taking  place  in  the  discharge  of  its  normal  functions.  Regard- 
ing the  complexity  of  reaction  presented  by  living  protoplasm  as  deter- 
mined in  the  first  instance  by  the  chemical  and  physical  complexity  of 
this  material  itself,  we  should  expect  to  find  that  the  proteins,  forming 
its  main  constituents,,  would  themselves  partake  of  some  of  this 
quality.  The  carbohydrates  and  fats,  although  iv  many  cases  made 
up  of  huge  molecules,  are  nevertheless  built  up  on  a  very  simple  type. 
Starch,  for  instance,  with  a  molecular  weight  of  over  30,000,  is 
formed  simply  by  the  polymerisation  of  glucose  molecules.  The 
ordinary  fats,  stearin  and  palmitin,  consist  of  fatty  acids  with  long 
straight  chains  of  CHg  groups,  combined  with  the  glyceryl  radical. 
Their  molecular  weight  is  very  large,  but  their  molecules  are  simple  in 
structure.  When,  however,  we  break  up  a  protein  molecule  we  meet 
with  a  great  number  of  subsidiary  groups,  the  presence  of  which  is 
essential  to  the  making  of  a  nutritive  protein. 

Owing  to  this  complexity  of  structure  it  is  not  easy  to  give  a  simple 
definition  in  chemical  terms  of  what  we  mean  by  the  term  '  protein.' 
It  is  necessary  rather  to  describe  certain  of  the  equalities  presented 
by  this  group,  the  possession  of  which  we  regard  as  essential  to  the 
conception  of  a  protein. 

EUmentani  Composition.  All  proteins  contain  oxygen,  hydrogen, 
nitrogeU;  carbon,  and  sulphur.  The  proportion  of  these  elements  in  the 
various  proteins  may  be  represented  as  follows  : 

C  50-6-54-5  per  cent. 
H  C-5-  7-3  „  „ 
N  15-0-17-6  ,.  „ 
S  0-3-  2-2  „  „ 
0  21-5-23-5  „  „ 
78 


THE  PROTEINS  79 

Nearly  all  the  proteins  contain  a  small  trace  of  phosphorus  varying 
from  0-4  to  0-8  per  cent.  It  is  doubtful,  however,  how  far  this  phos- 
phorus forms  an  integral  part  of  the  protein  molecule. 

Physical  Characters.  The  proteins  are  amorphous  indiiiusible 
substances  belonging  to  the  class  of  bodies  known  as  colloids.  Most 
of  them  are  soluble  either  in  water,  weak  salt  solutions,  or  in  dilute 
acids  or  alkaUes.  They  are  inert  bodies  and  tasteless.  Although  they 
form  compounds  with  various  metallic  salts,  acids,  or  alkalies,  these 
compounds  are  but  ill  defined,  and  the  relative  proportions  of  the 
ingredients  vary  according  to  the  conditions  under  which  the  com- 
pound was  formed.  As  is  the  case  with  most  colloids  when  in  solu- 
tion or  pseudo-solution,  they  can  be  brought  into  an  insoluble  form 
by  various  simple  agencies,  such  as  shaking,  change  of  temperature, 
alteration  of  reaction,  or  addition  of  neutral  salts.  Coagulation 
by  heat  forms  a  distinguishing  feature  of  a  number  of  members  of 
this  class,  which  are  therefore  spoken  of  as  '  coagulable  proteins.' 
For  instance,  white  of  egg  is  a  solution  of  different  proteins.  On 
diluting  it  with  weak  salt  solution  no  precipitation  takes  place.  If, 
however,  the  solution  be  heated  to  about  80°  C.  a  precipitate  of  coagu- 
lated protein  is  formed.  If  a  strong  solution  be  boiled  the  whole 
fluid  sets  to  a  solid  white  mass  (hydrogel).  This  change  is  irrever- 
sible, i.e.  it  is  not  possible  by  lowering  the  temperature  to  bring  the 
white  of  egg  again  into  solution,  and  many  properties  of  the  protein 
have  been  changed  in  the  act  of  coagulation.  With  certain  proteins 
and  their  allies  the  coagulation  on  change  of  temperature  is  a  reversible 
process.  Thus  an  alkahne  solution  of  caseinogen,  the  chief  protein 
of  milk,  if  treated  with  a  little  calcium  chloride  and  heated,  undergoes 
coagulation  and  sets  into  a  jelly,  but  on  cooling  the  mixture  the 
coagulum  once  more  enters  into  solution.  Ordinary  gelatin,  which 
is  closely  alUed  to  the  proteins,  with  water  forms  a  solid  jelly  below 
20°  C,  and  a  fluid  solution  above  this  temperature. 

If  a  protein  be  heated  in  a  current  of  air  or  oxygen  it  undergoes 
combustion.  In  all  cases  a  certain  amount  of  incombustible  material 
is  left,  consisting  of  inorganic  salts  which  were  closely  attached  to 
the  protein  molecule.  If  a  solution  of  protein  be  subjected  to  long- 
continued  dialysis,  the  proportion  of  ash  may  be  diminished  very  largely, 
but  in  no  case  has  any  experimenter  succeeded  in  obtaining  a  pre))ara- 
tion  of  protein  absolutely  ash-free.  On  this  account  it  has  beeji 
thought  that  the  salts  of  the  ash  nuist  be  in  chemical  combination 
with  the  protein  ;  but  having  regard  to  the  physical  character  of 
colloidal  solutions,  which  we  shall  study  in  the  ne.xt  chapter,  and  the 
power  of  adsorption  of  substances  possessed  by  such  solutions,  there 
is  no  need  to  regard  these  salts  as  essential  constituents  oi  the  protem. 

Cnjstallisalion  of  Prntcin.s.     Altliou^li  the  indilTusihility  of  protvin 


80  PHYSIOLOGY 

solutions  differentiates  them  from  the  crystalloid  substances  such 
as  sugar  or  sodium  chloride,  under  certain  conditions  it  is  possible 
to  obtain  crystals  consisting,  largely  at  any  rate,  of  proteins.  Thus 
in  the  seeds  of  certain  plants,  e.g.  hemp  seeds,  Brazil  nut,  pumpkin, 
and  castor-oil  seeds,  the  so-called  aleurone  crystals  may  be  seen 
under  the  microscope  enclosed  in  the  protoplasm  of  the  cells.  These 
crystals  consist  of  proteins  belonging  to  the  class  of  globulins.  By 
chemical  means  they  can  be  separated  from  the  surrounding  tissues 
and,  after  washing,  dissolved  in  a  solution  of  magnesia.  Drechsel 
showed  that  on  dialysing  such  a  solution  against  alcohol,  the  fluid 
undergoes  gradual  concentration,  and  crystalline  granules  of  the 
magnesia  compound  of  the  protein  separate  out.  These  crystals 
contain  r4  p.c.  MgO.  A  better  method  of  obtaining  such  crystals 
has  been  devised  by  Osborne.  The  ground  seeds  are  extracted  with 
10  per  cent,  sodium  chloride  solution,  and  filtered.  The  filtrate  is 
diluted  with  water  heated  to  50°  or  60°  C.  until  a  slight  tuibidity  forms. 
After  warming  the  diluted  solution  until  this  turbidity  disappears,  and 
then  allowing  it  to  cool  slowly,  the  protein  separates  in  well-developed 
crystals.  It  is  possible  also  to  obtain  crystals  of  animal  proteins. 
Haemoglobin,  the  oxygen-carrying  protein  of  the  red  blood  corpuscles, 
can  be  made  to  crystaHise  with  extreme  ease.  With  some  animals, 
such  as  the  rat,  it  is  only  necessary  to  bring  the  haemoglobin  into 
solution,  by  the  addition  of  a  little  distilled  water  and  ether  to  the 
blood,  to  cause  the  crystallisation  of  the  liberated  hasmoglobin. 

Egg  albumin  and  serum  albumin  may  also  be  crystallised  with 
ease  by  a  method  dev^ised  by  Hofmeister  and  improved  by  Hopkins. 
If,  for  instance,  we  wish  to  crystallise  egg  albumin,  white  of  eggs  is 
treated  with  an  equal  bulk  of  saturated  solution  of  ammonium  sul- 
phate in  order  to  precipitate  the  globulin.  It  is  then  filtered,  and  the 
filtrate  is  treated  with  saturated  ammonium  solution  until  a  slight 
permanent  precipitate  is  produced.  This  precipitate  is  then  just 
redissolved  by  the  cautious  addition  of  water,  and  dilute  acetic  acid 
(10  per  cent.)  is  added  drop  by  drop  until  a  slight  precipitate  is 
produced.  The  flask  is  now  corked  and  allowed  to  stand  for  twenty- 
four  hom-s,  when  the  precipitate,  which  will  have  increased  in  quantity, 
will  be  found  to  consist  entirely  of  acicular  crystals.  A  similar  method 
may  be  used  for  serum  albumin.  In  each  case  the  crystals  contain 
a  considerable  proportion  of  ammonium  sulphate.  This  may  be 
replaced  by  sodium  chloride  by  washing  the  crystals  with  a  saturated 
solution  of  this  salt.  By  absolute  alcohol  the  crystals  may  be 
coagulated  and  may  be  then  washed  practically  free  from  salt,  but  it  is 
not  possible  to  obtain  crystals  of  coagulable  j)rotein  free  from  the 
presence  of  some  salt. 

Although  by  repeated  crystallisation  of  egg  albumin  a  product 


THE  PROTEINS  81 

may  be  obtained  which  is  absolutely  constant  in  both  its  pliysical  and 
chemical  characters,  we  cannot  ascribe  to  crystallisation  the  same 
importance  in  securing  purity  and  homogeneity  of  the  substance 
that  we  can  when  we  are  dealing  with  inorganic  salts.  This  is  due 
to  the  fact  that  these  crystals  take  up  other  colloids  with  great  ease. 
When  hajmoglobin,  for  instance,  is  crystallised  from  blood,  the  first 
crop  of  crystals,  although  thoroughly  washed  from  their  mother  liqu(u-, 
always  contain  a  considerable  proportion  of  serum  albumin.  Indeed, 
the  presence  of  colloidal  material  seems  to  render  the  production  of  the 
so-called  mixed  crystals  much  more  easy.  Thus  Schultz  has  shown 
that  in  luine  mixed  inorganic  crystals  can  be  obtained.  Human 
urine  is  allowed  to  stand  twenty-four  to  forty-eight  hours  with  di- 
calcium  phosphate  and  then  filtered.  On  allowing  the  filtrate  to 
evaporate  slowly,  a  crystalline  precipitate  is  produced  consisting  of 
whetstone-shaped  crystals  which  are  doubly  refracting.  On  treating 
these  crystals  with  dilute  acetic  acid  this  acid  extracts  calcium  phosphate 
from  the  crystals.  The  original  shape  of  the  crystals  is,  however,  retained. 
The  only  difference  under  the  microscope  consists  in  the  fact  that  they 
have  now  lost  their  doubly  refracting  power  on  polarised  light.  They 
consisted  of  a  mixture  of  calcium  sulphate  and  calcium  phosphate,  from 
which,  on  treatment  with  acid,  only  the  calcium  phosphate  was  dis- 
solved out. 

The  Molecular  Weight  of  Proteins.  We  may  arrive  at  an  approxi- 
mate idea  of  the  minimum  size  of  the  protein  molecule  in  various  wavs, 
though  in  all  cases  our  calculations  are  apt  to  be  vitiated  by  the  diffi- 
culty of  obtaining  a  preparation  which  is  homogeneous,  i.e.  chemically 
pure,  and  by  the  ease  with  which  molecules  of  the  size  which  we  must 
assume  for  proteins  form  adsorption  combinations  in  varying  propor- 
tions with  other  substances.  If  we  assume  that  each  molecule  of 
the  respective  protein  contains  only  one  atom  of  sulphur,  we  can 
calculate  its  molecular  weight.  It  is  evident  that  the  protein  which 
contains  1  per  cent,  of  sulphur  will  have  a  molecular  weight  of  32(H). 
In  this  way  the  following  molecular  weights  have  been  arrived  at 
(Abdcrhalden) : 

Sulphur  per  cent.        Molecular  weight 
Edestin       .  .  0-87  ..  3680 

Oxyhaauioglobin  .  0-43  .  .  7440 

(horse) 
Serum  albumin     .  1-89  ..  1700 

(horse) 
Egg  albumin  1-30  .,  2400 

Globulin     .  1-38  ..  2320 

The  greater  part  at  any  rate  of  the  sulphur  in  the  protein  molecule 
occurs  as  a  constituent  of  a  substance,  cystine,  each  molecide  of  which 
contains  two  atoms  of  sulphur.     Each  molecule  of  protein  must  also 


82  PHYSIOLOGY 

contain  two  atoms  of  sulphur,  and  we  must  regard  double  the  molecular 
weight  given  in  this  table  as  the  minimum  molecular  weights  of  these 
various  proteins.  Some  idea  of  the  molecular  complexity  repre- 
sented by  these  weights  may  be  gained  by  A\Titing  out  the  empirical 
formulae  of  the  various  proteins,  e.g.. 

Egg  albumin C204  H322  '^520  A 

Protein  in  haemoglobin  (from  horse)      .        .  C680H1098N210O241S2 

Protein  in  haemoglobin  (from  dog) .        ,        .  07351111711^194021482 

CrystaUised  globulin  (from  pumpkin  seeds)  C292H4giN2o083S2 

With  some  proteins  we  may  make  use  of  other  elements  to  arrive 
at  an  idea  of  the  approximate  molecular  weight.  Thus,  oxyhsemo- 
globin  contains  between  0-4  and  0-5  per  cent  iron.  If  we  assume 
that  each  molecule  of  oxyhsemoglobin  contains  one  atom  of  iron,  its 
molecular  weight  must  be  from  11,200  to  14,000. 

Attempts  have  been  made  to  solve  the  same  question  by  studying 
the  compounds  of  proteins  with  inorganic  salts  or  oxides.  Thus, 
the  crystals  of  globulin  from  pumpkin  seeds  prepared  with  magnesia 
contain  1-4  per  cent.  MgO.  Assuming  that  one  molecule  of  protein 
has  combined  with  one  molecule  MgO,  the  molecular  weight  of  the 
protein  must  be  about  2800. 

(If  a;  be  the  molecular  weight 

X         100-1-4 


40  1-4 

.-.  a;  =  2817) 

Harnack  has  shown  that  many  proteins  are  precipitated  from 
their  solutions  as  a  copper  compound  by  the  addition  of  copper 
sulphate.  Harnack  found  that  this  precipitate  of  copper  contained 
either  1-34 -1-37  Cu.  or  2-48 -2-73  per  cent.  Cu.  The  smaller 
percentage  would  correspond  to  a  molecular  weight  of  4700,  while 
the  second  number  might  be  accounted  for  on  the  hypothesis  that 
each  molecule  of  protein  was  combined  with  two  atoms  of  copper. 
Similar  attempts  have  been  made  by  determining  the  amount  of  acid 
or  alkali  necessary  to  keep  certain  types  of  protein  in  solution.  We 
shall  see  later  on,  however,  that  the  amounts  vary  largely  with  the 
physical  condition  and  previous  history  of  the  colloidal  substance. 
We  are  dealing  here  not  with  compounds  in  the  strict  chemical  sense 
of  the  term,  but  with  adsorption  compounds,  where  the  quantities 
taken  up  are  determined  not  only  by  the  chemical  nature  of  the  protein 
itself,  but  by  the  state  of  aggregation  of  its  molecules.  It  is  therefore 
impossible  to  lay  any  great  stress  on  the  determinations  of  the  mole- 
cular weight  which  have  been  effected  in  this  way. 


THE  PROTEINS  83 

8ome  clue  to  the  size  of  the  protein  molecule  is  afforded  by  deter- 
minations of  the  osmotic  pressure  or  molecular  concentration  of 
their  solutions  by  physical  methods.  When  we  determine  the  freez- 
ing-point or  boihng-point  of  protein  solutions,  the  depression  of 
freezing-point,  or  elevation  of  boiling-point,  is  so  small  that  it  falls 
within  the  limit  of  experimental  error  or  is  no  greater  than  can  be 
accounted  for  by  the  inorganic  salts  present  in  the  solution.  Since, 
however,  colloidal  membranes,  such  as  films  of  gelatin  or  vegetable 
parchment,  are  impervious  to  proteins,  we  can  directly  determine  the 
osmotic  pressure  of  their  solutions.  In  many  cases  no  osmotic 
pressure  whatever  is  found.  In  other  cases,  e.g.  egg  albumin,  or 
serum,  the  colloidal  constituents  of  these  solutions  are  found  to  give 
an  osmotic  pressure  of  such  a  height  that  1  per  cent,  protein  corre- 
sponds to  about  4  mm.  Hg.  pressure.  Such  an  osmotic  pressure 
would  indicate  a  molecular  weight  for  the  serum  proteins  of  about 
30,000.  A  determination  of  the  osmotic  pressure  of  haemoglobin  by 
Hiifner  gave  a  molecular  weight  about  16,000.  These  results,  however, 
must  be  received  with  caution,  since  we  are  not  justified  in  applying 
to  these  gigantic  molecules  data  derived  from  a  study  of  smaller  mole- 
cules such  as  salt  or  sugar.  Even  if  we  accept  these  determinations 
of  osmotic  pressure  as  indicating  the  molecular  weights  I  have  just 
quoted,  it  is  evident  that  a  very  slight  degree  of  aggregation  of  the 
molecules  into  larger  complexes  will  bring  the  osmotic  pressure  below 
the  point  at  which  it  is  measurable,  and  would  transform  the  solution 
into  a  suspension  of  particles  in  which  one  could  not  expect. to  find  any 
osmotic  pressure  whatsoever. 

THE  STRUCTURE  OF  THE  PROTEIN  MOLECULE 

We  can  arrive  at  some  idea  of  the  manner  in  which  the  protein 
molecule  is  built  up  only  by  breaking  it  down  bit  by  bit,  employing 
methods  which,  while  resolving  the  large  molecule  into  its  proximate 
constituents,  will  not  act  too  forcibly  in  changing  the  whole  arrange- 
ments of  these  constituents.  The  relation  of  the  starches  or  poly- 
saccharides to  the  sugars  was  found  by  studying  the  hydrolysis  of  the 
former,  and  it  is  by  the  hydrolysis  of  the  proteins  that  we  have  arrived 
at  most  of  our  present  knowledge  of  their  constitution.  Contributory 
evidence  may  also  be  gained  by  the  use  of  oxidising  agents  or  by 
employing  the  refined  methods  of  analysis  possessed  by  certain 
living  organisms — ^bacteria,  by  wliicli  means  we  can  effect  limited 
oxidations  or  reductions  or  can  replace  an  NHg  group  by  H,  or  a  COOK 
group  by  H. 

ACID  HYDROLYSIS  OF  PROTEINS.  For  this  purpose  rather 
stronger  acids  are  used  than  for  the  hydrolysis  of  starch.  The  pro- 
tein is  heated  for  twenty-four  hours  in  a  flask  fitted  with  a  reflux 


84  PHYSIOLOGY 

condenser  either  with  concentrated  hydrochloric  acid  or  with  a  25 
per  cent,  snlphnric  acid.  Hydrochloric  acid  was  first  made  use  of 
by  Hlasiwetz  and  Habermann,  who  added  a  certain  amount  of 
stannous  chloride  to  the  mixture  in  order  to  prevent  any  oxidation 
taking  place.  We  obtain  in  this  way  an  acid  fluid  containing  an 
extremely  complex  mixture  of  various  substances,  all  of  which  belong 
to  the  class  of  amino-acids,  and  must  be  regarded  as  the  proximate 
constituents  of  the  protein  molecule. 

A  similar  hydrolytic  change  may  be  effected  by  the  use  of  digestive 
ferments  obtained  either  from  the  ahmentary  canal  of  higher  verte- 
brates or  from  certain  plants.  Thus  we  may  use  pepsin,  the  active 
constituent  of  the  gastric  juice,  trypsin,  the  proteolytic  ferment 
secreted  by  the  pancreas,  papaine  or  other  vegetable  ferments  obtained 
from  papaya,  from  pineapple  juice,  and  so  on.  These  ferments  are 
all  milder  in  their  action  than  the  strong  acids.  Pepsin,  for  instance, 
only  effects  a  partial  decomposition  of  the  protein  molecule.  Its 
action  results  in  the  formation  of  substances  which  still  present 
all  the  protein  reactions  and  are  classified  as  hydrated  proteins 
or  as  proteoses  and  peptones.  Trypsin  carries  the  protein  a  stage 
further  and  gives  a  mixture  of  amino-acids.  Certain  groups^  however, 
of  the  protein  molecule  present  a  considerable  resistance  to  the 
action  of  trypsin,  so  that  when  its  action  is  complete  these  groups 
are  still  found  not  yet  broken  down  into  their  constituent  amino- 
acids. 

The  putrefactive  processes  determined  by  the  presence  of  bacteria 
in  solutions  of  proteins  are  somewhat  too  complicated  in  their  results 
to  throw  much  illumination  on  the  structure  of  the  protein  molecule 
itself.  This  method  is,  however,  of  extreme  value  when  it  is  applied 
to  isolated  constituents  of  the  proteins.  Under  the  action  of  these 
bacteria  we  may  have  a  process  of  deamination  which  may  be 
accompanied  by  simple  hydrolysis  or  by  reduction.  In  the  former 
case  an  amino-acid  may  be  converted  into  an  oxyacid,  in  the  latter 
case  into  a  fatty  acid. 

Thus  tyrosine  under  the  action  of  bacteria  of  putrefaction  may 
split  up  into  ammonia  and  oxy phenyl  propionic  acid. 

OH .  CfiH^ .  CH2 .  CHNH2 .  COOH  +  H2  = 
HO .  CcH^ .  CH, .  CH. .  COOH  +  NH3 

Under  the  action  of  yeasts  an  amine  may  become  an  alcohol. 

C5H11 .  NH2  +  H2O  -  C^Hn .  OH  +  NH3 
(amylamine)  (amylalcohol) 

On    the  other  hand,  the    effect    of  the  bacteria  may  be    to  split 


THE  PROTEINS  85 

off  carbon  dioxide  from   the   amino- acids.     Thus,  the  diamino-acid, 
lysine, 

CHa^^Ho  ('H.,NH, 


CH2 
CH., 


becomes 


( 'Ho  pentamethylene  diamine. 
(JH., 


CH.NH, 


CH,NH, 


COOH 

Tyrosine  becomes  p.  oxyphenylethylamine,  a  substance  having 
marked  physiological  effects,  and  an  important  constituent  of  ergot. 
Phenylalanine  CeHj.CHg.CH.NHa-COOH,  becomes  phenylethyla- 
mine  CgHs.CHa.CHa.NHg.  These  reactions  are  therefore  of  value 
in  determining  the  exact  grouping  of  the  atoms  in  the  more  complex 
of  the  proximate  constituents  of  the  proteins. 

Since  all  the  known  disintegration  products  of  the  proteins  belong 
to  the  class  of  amino-acids,  it  may  be  of  value  to  point  out  some  of  the 
distinp:uishing  features  of  this  class  of  bodies. 

PROPERTIES  OF  AMINO-ACIDS.  An  amino-acid  is  derived 
from  an  organic  acid  by  the  replacing  of  one  atom  of  hydrogen  by  the 
amino  group  NHg.     Thus  from  the  acids, 


acetic  acid 
CH, 


propionic  acid 

CH, 


COOH 


CH., 


we  may  obtain  the  mono-amino-acids, 


COOH 


amino-acetic  acid  alanine  or  «-aniino-propionic  acid 


CH2NH2 


COOH 


CH, 


CH.NH, 


COOH 

It  will  be  noticed  that  in  the  fatty  acids  witli  moro  than  two  at<inis 
of  carbon  the  position  of    the   NHg  group  may  be   varied.     Thus, 


■•2 


86  PHYSIOLOGY 

instead  of  alanine  we  may  have  another  amino- propionic  acid, 
namely  : 

CH2NH2 

I 

I 
COOH 

This  acid  would  be  spoken  of  as  /5-araino- propionic  acid,  alanine 
being  cramino-propionic  acid.  This  nomenclature  is  always  used  to 
distinguish  the  position  of  the  NHg  group,  so  that  we  may  have  mono- 
amino-acids  a,  /3,  y,  S,  e  •  •  •  and  so  on.  Practically  all  the  amino- 
acids  which  occur  as  constituents  of  the  protoplasmic  molecule  belong 
to  the  a  group. 

On  inspection  of  the  formula  of  glycine  it  is  evident  that  only  one 
isomer  of  this  body  is  possible.  In  alanine,  however,  the  carbon  atom 
to  which  NH2  is  attached  is  asymmetric,  since  its  four  combining 
ajSinities  are  each  attached  to  different  groups.     Thus  : 

C 
H— C— NH2 

C 

In  this  case,  therefore,  there  is  a  possibility  of  stereoisomerism,  and 
alanine  must  have  an  influence  on  polarised  light.     If  the  compound 

CH3 
HCNH, 

COOH 

is  dextro-rotatory,  then  its  stereoisomer 

CH3 

I 
.   H2NCH 

COOH 

will  be  laevo-rotatory,  and  it  will  be  possible  to  obtain  a  racemic 
modification  without  any  influence  on  polarised  light  by  mixing 
equal  molecules  of  these  two  isomeric  forms.  All  the  amino-acids 
derived  from  proteins  are   optically  active,  whereas  those  obtained 


■^2 


■•2 


THE  PROTEINS  87 

by  synthesis  are  inactive,  and  special  means  have  to  be  devised  in  order 
to  obtain  from  the  artificially  formed  lacemic  amino-acid  either  the 
d-  or  /-amino-acid. 

If  more  than  one  hydrogen  atom  in  an  organic  acid  be  replaced 
by  NH2  we  obtain  diamino-  and  triamino-acids.  Thus,  ornithine, 
obtained  by  the  splitting  up  of  arginine,  one  of  the  commonest  dis- 
integration products  of  protein,  is  a-g-diamino- valerianic  acid. 

I 
CH2 

CH.XH2 

COOH 

The  presence  in  the  amino-acids  of  the  basic  radical  XHj  and  of 
the  acid  group  COOH  lends  to  these  bodies  a  double  character.  In 
themselves  devoid  of  strong  chemical  quahties.  possessing  neither  acid 
nor  alkaline  reaction,  they  are  able  in  the  presence  of  strong  acids 
or  bases  to  act  either  as  base  or  acid.  When  in  solution  by  themselves 
it  is  possible  that  there  is  an  actual  closing  of  the  ring  by  a  soluble  union 
between  the  NHg  group  and  the  COOH  gToup,  so  that,  e.g.  the  formula 
of  glycine  may  be  : 

CH2— NH3 

CO  — 0 

When  such  a  neutral  compound  is  treated  with  acid  this  bond  is  loosed 
and  we  have  the  salt  of  the  amino-acid.  Thus,  with  hydrochloric 
acid,  glycine  forms  glycine  hydrochlorate  : 

CH2NH2HCI 

I 
COOH 

a  salt  which  still  possesses  an  acid  group  and  which  is  therefore  capable 
of  combining  with  ethyl  to  form  the  hydrochlorate  of  the  (\st»n-  of  the 
amino-acid.     Thus : 

CH2.NH2HCI 

I 
COOCH, 


88  PHYSIOLOGY 

With  bases  the  amino-acids  form  salt-like  compounds  such  as  potassium 
ami  no-acetate  : 

CHoNH, 


12-^'' -^^2 


COOK 

With  neutral  salts  crystalline  compounds  may  be  also  formed.  With 
sodium  chloride  glycine  will  form  the  double  salt  CaHgNOg-NaCl, 
which  may  perhaps  be  represented  : 

CH2NH3CI 

COONa 

Not  only  do  the  amino-acids  form  compounds  with  salts,  but  they  also 
combine  with  one  another.  This  power  of  combination  much 
increases  the  difl&culty  of  separating  the  constituents  from  a  mixture 
of  amino-acids,  Amino-acids,  which  singly  are  extremely  insoluble, 
are  readily  soluble  when  in  the  presence  of  other  amino-acids. 

On  account  of  the  dual  nature  of  the  amino-acid  molecule,  these 
substances  act  as  feeble  conductors  of  the  electric  current,  i.e.  as 
electrolytes.  The  charge  carried  by  an  amino-acid  and  its  ionisation 
depends  upon  the  conditions  in  which  it  is  placed.  Since  it  may 
act  either  as  the  cation  or  the  anion,  it  is  spoken  of  as  an  amphoteric 
electrolyte. 

One  reaction  of  the  amino-acids  is  of  special  interest  in  connection 
with  the  respiratory  functions  of  the  body,  namely,  the  formation  of 
carbamino-acids.  If  a  stream  of  carbon  dioxide  be  passed  into  a 
mixture  of  an  amino-acid,  e.g.  glycine,  with  lime,  the  carbon  dioxide 
is  taken  up.  On  filtering  the  mixture  a  clear  liquid  passes  through 
which  gradually  in  course  of  time  deposits  a  precipitate  of  calcium 
carbonate.  The  filtrate  first  obtained  contains  a  compound  of  cal- 
cium, calcium  glycine  carbonate.     The  formula  is  as  follows  : 


0H2 

.NH 

^COO 

coo  Ca 

METHODS  OF  SEPARATING  AMINO-ACIDS.  By  the  hydrolysis 
of  protein  by  means  of  acid  or  of  trypsin,  we  obtain  a  complex  mixture 
of  amino-acids.  From  this  mixture  certain  amino-acids  are  separated 
with  ease.  Thus,  tyrosine,  which  is  extremely  insoluble,  crystallises 
out  on  concentrating  the  fluid,  and  further  concentration  leads  to  the 
separation  of  leucine.  The  other  acids,  which  keep  each  other  mutually 
in  solution,  are  however  very  difficult  to  isolate.     We  owe  to  Fischer 


THE  PROTEINS  89 

the  first  general  method  for  their  separation.      We  may  take  one 
experiment  as  an  example. 

rive  hundred  grammes  of  casein  are  heated  for  some  hours  under  a  reflux 
condenser  with  1 J  litres  of  strong  hydrochloric  acid.  Tho  liquid  is  then  saturated 
Avith  gaseous  hydrochloric  acid  and  allowed  to  stand  for  three  days  in  the  ice- 
chest.  Crystals  of  hydrochlorate  of  glutamic  acid  separate  out.  The  filtrate 
from  these  crystals  is  evaporated  at  40°  C.  under  diminished  pressure  to  a  syrupy 
consistence,  and  is  then  dissolved  in  1|  litres  of  absolute  alcohol.  Hydrochloric 
acid  is  then  passed  into  the  solution  to  complete  saturation,  the  mixture  being 
warmed  for  a  short  time  on  tho  water  bath,  and  the  mixture  is  once  more  evapo- 
rated to  a  sj^rupy  consistence.  3y  tliis  treatment  all  the  amino-acids  have  been 
converted  into  the  hydrochlorates  of  their  esters,  e.g. : 

CHoNHoHCl  C2H4NH2HCI 

r  "  ! 

COOaH.  COOCoHb  &c. 


From  the  hydrochlorates  the  esters  are  set  free  by  the  addition  of  potassium 
carbonate,  the  mixture  being  cooled  in  a  freezing  mixture.  By  this  means  the 
esters  of  aspartic  and  glutamic  acids  are  separated  and  are  extracted  by  shaking 
with  ether.  The  remaining  esters  are  then  liberated  by  the  addition  of  33  per 
cent,  caustic  soda  together  with  potassium  carbonate,  and  are  again  extracted 
by  ether.  The  combined  ethereal  solutions  are  dried  by  standing  over  fused 
sulphate  of  soda  and  then  evaporated,  when  a  residue  containing  the  free  esters 
is  obtained.  These  esters  are  then  separated  by  fractional  distillation  under 
a  very  low  pressure  obtained  by  means  of  the  Fleuss  pump,  the  second  receiver 
of  the  apparatus  being  cooled  in  liquid  air.  The  various  fractions  of  amino- 
csters  obtained  in  this  Avay  are  hydrolysed — the  lower  fractions  by  boiling  for 
some  hours  vrith  water,  the  higher  fractions  b}'  boiling  with  baryta.  The  acids 
obtained  by  the  hyckolj^sis  can  then  be  further  purified  by  means  of  fractional 
crystallisation. 


THE   DISINTEGRATION  PRODUCTS    OF  THE  PROTEINS 

By  the  methods  just  described  the  following  substances  have  been 
isolated  from  proteins : 

A.     FATTY  SERIES 
(1)     Mono-a^nino-acids  [Monobasic) 

GLYCINE   or   GLYCOCOLL.     This,   the   simplest  member   of   the 
group,  is  amino-acetic  acid  : 

CH2NH2 

I 
COOH 

It  occurs  in  considerable  quantities  among  the  disintegi'ation  products 
of  gelatiu  and  to  a  slight  extent  among  those  derived  from  cortaiu  of 
the  proteins.  Like  the  other  , (-amino-acids,  it  has  a  sweetish  taste, 
whence  its  name  was  derived  {yXvKocr  =  sweet,  koXXii  =  glue). 


90  PHYSIOLOGY 

ALANINE  is  a-amino-propionic  acid  : 

CH3 

CH.NH2 

COOH 

It  is  optically  active,  the  alanine  derived  from  proteins  being  dextro- 
rotatory. 

Closely  allied  to  alanine  is  the  amino-acid  SERINE,  which  was  first 
obtained  by  the  hydrolysis  of  silk  and  has  since  been  found  as  a  con- 
stituent of  a  large  number  of  proteins.     Its  formula  is  : 

CH2OH 

! 
CH.NH2 

COOH 

i.e.  it  is  amino- oxy propionic  acid.  Its  special  interest  lies  in  the  fact 
that  it  was  one  of  the  first  of  the  amino-oxyacids  to  be  isolated,  and  it 
is  possible  in  these  acids  that  we  must  seek  the  intermediate  stages 
between  carbohydrates  and  proteins. 

AMINO-VALERIANIC  ACID  has  the  formula 
OH3   CH3 

\/ 
CH, 

CH.NH2 

COOH 

It  occurs  only  in  small  quantities  in  the  protein  molecule. 

LEUCINE,  one  of  the  oldest  known  members  of  the  group  of  amino- 

acids,  is  obtained  in  large  quantities  from  the  disintegration  of  nearly 

all  the  animal  proteins,  of  which  in  some  cases  it  may  form  as  much  as 

20  per  cent.     It  has  the  formula 

OH  3  CH3 

\/ 
CH 

I 
CH2 

CH.NH2 

COOH 

i.e.  it  is  amino-isobutyl  acetic  acid.     On  evaporating  a  tryptic  digest 


THE  PROTEINS  91 

of  protein,  impure  leucine  crystallises  out  in  the  form  of  imperfect 
crystals,  the  so-called  '  leucine  cones.' 

Lately  another  isomer  of  leucine  has  been  discovered,   namely,  «-aniino- 
methyl  ethyl  propionic  acid.     This  is  called  isoleucine. 

(2)    Mono-amino  Derivatives  of  Dibasic  Acids 
Of  these  two  are  known,  namely,  aspartic  and  glutamic  acids. 
ASPARTIC  ACiD  is  (<-amino-succinic  acid  : 

COOH 

CH.NH2 

CH2 

COOH 

and  glutamic  acid  is  the  next  homologue,  namely,  a-amino-glutaric 
acid  : 

COOH 

CH.NH, 

I 
CH, 

CH2 

COOH 

Owing  to  the  possession  of  two  carboxyl  groups  these  amino-acids  have 
a  much  more  pronounced  acid  character  than  is  the  ca^e  with  the 
other  members  of  the  group  which  we  have  been  studpng. 

Aspartic  acid  was  first  found  in  the  shoots  of  .vsparagus  in  the  form  of  the 
amide,  asparaginc  : 

COOH 

I 
CHNH, 

I 
CH2 

I 
CONHo 

This  .substance  is  very  widely  distributed  throughout  the  vegetable  kingdom 
and  is  present  in  .seedlings  in  very  large  quantities,  as  much  as  25  per  cent, 
of  the  dried  weight.  In  plants  it  apparently  serves  either  as  a  reserve  material 
or  as  the  form  in  which  the  greater  part  of  the  nitrogen  is  convoyed  from  the 
reserve  organs  to  be  built  up  into  the  protoplasm  of  the  growing  parts  of  the 
plant. 


92  PHYSIOLOGY 

(3)     Diamino-acids 

Of  these  two  are  known,  namely,  lysine  and  arginine.  Owing  to 
the  presence  of  two  NHg  groups  in  their  molecule,  they  all  possess 
marked  basic  characters,  and  are  precipitated  from  the  acid  solution 
obtained  by  the  hydrolysis  of  proteins  on  adding  phosphotungstic 
acid.  Since  lysine,  arginine,  and  histidine  (another  amino-acid  which 
will  be  described  later)  all  contain  six  carbon  atoms  in  their  molecule, 
these  three  bodies  were  classed  together  by  Kossel  as  the  '  hexone  ' 
bases.  Apart,  however,  from  their  high  content  in  nitrogen,  the 
chemical  resemblance  between  these  bodies  is  no  closer  than  between 
them  and  the  other  members  of  the  amino-acid  series. 

Another  body  isolated  by  Fischer  in  small  quantities  is  supposed 
to  belong  to  this  class  and  to  have  the  composition  diamino-trioxy- 
dodecoic  acid. 

LYSINE  CgHi4N202  is  a-e-diamino-caproic  acid  having  the  formula 

CH2NH2 

CH.NH2 

COOH 

ARGININE,  which  was  first  discovered  in  plants  (the  cotyledons  of 
lupins),  is  not  a  simple  amino-acid,  but  a  compound  of  an  amino-acid 
with  guanidin.  If  boiled  with  baryta  water  it  splits  up  into  urea  and  a 
substance  reacting  as  a  base  which  was  called  ornithine.* 

ORNITHINE,  diamino- valerianic  acid,  has  the  formula 

CHoNH, 

CH.NH2 

COOH 

The  constitution  of  arginine  is  analogous  to  that  of  creatine,  one  of 
the  most  abundant  nitrogenous  extractives  of  muscle. 
CREATINE  has  the  formula 


HN  =  C 


H,N 


-N(CH3)CH2COOH 


*  Ornithine  had  been  previously  discovered  in  tlie  urine  of  fowls,  after  the 
administration  of  benzoic  acid,  in  the  form  of  an  acid  known  as  ornithuric  acid. 


THE  PROTEINS 


^3 


It  is  methyl  guanidine  acetic  acid.  On  boiling  creatine  with  baryta 
water  it  takes  up  a  molecule  of  water  and  splits  in  tlie  situation  of  the 
dotted  line  in  the  formula,  giving 


H^N 


\n, 


CO  (m-ea)  and  NH(CH3)C'H2COOH  (methyl  glycine). 


H^N' 


This  latter  substance  is  known  as  sarcosine  and  is  derived  from  glycine 
by  the  replacement  of  one  atom  of  hydrogen  by  a  methyl  gi-oup  CH^. 

Arginine  has  a  similar  formula.  On  the  left-hand  side  of  the  dotted 
line  the  formula  would  be  identical  with  that  of  creatine.  On  the  right- 
hand  side  the  sarcosine  group  is  replaced  by  a  diamino-acid  of  the  fatty 
series,  diamino- valerianic  acid. or  ornithine. 

DIAMINO-TRIOXYDODECOIC  acid  is,  as  its  formula  implies,  a 
derivative  of  a  twelve-carbon  acid.  Its  constitutional  formula  has  not 
yet  been  made  out. 

B.     AMINO-ACIDS  CONTAINING   AN   AROMATIC  NUCLEUS 
The  best  known  of  these  is  TYROSINE,  which  has  the  formula 

OH 


CkH4 


CH0CH.NH2COOH 

It  is  paraoxyphenyl  a-alanine.  It  is  one  of  the  first  of  the  amino- 
acids  to  be  split  off  from  the  protein  molecule  under  the  influence  of 
hydrolytic  agents.  Owing 
to  its  insolubility  it 
rapidly  separates  out  as 
bundles  of  fine  needle- 
shaped  crystals  at  the 
sides  and  bottom  of  the 
vessel. 

When  tyrosine  is 
treated  with  an  acid  solu- 
tion of  mercuric  nitrate 
containing  a  Httle  nitrous 
acid,  a  precipitate  is 
produced,  and  on  boiling, 
the  precipitate  and  the 
supernatant  fluid  assume 
a  deep  red  colour.  This 
reaction   is    given  by   all 


Fig.   is.     Tyrosine  crystals.     (Pumsieb.) 


94  PHYSIOLOGY 

benzene  derivatives  in  which  one  atom  of  hydrogen  in  the  ring  is 
replaced  by  one  OH  group.  This  is  known  as  HofEmann's  test,  but 
is  identical  with  Millon's  reaction,  which  is  given  by  all  proteins  con- 
taining tyrosine  in  their  molecules. 

Closely   allied   to   the   foregoing  compound   is   another   aromatic 
amino-acidj  namely,  phenyl  a-alanine  : 


CrHk 


CH2CH.NH2COOH 


It  is  an  almost  constant  constituent  of  proteins. 

TRYPTOPHANE  was  known  long .  before  it  had  been  isolated, 
owing  to  the  fact  that  with  bromine  water  it  gives  a  rose-red  colour. 
It  had  long  been  observed  that  this  substance  was  to  be  obtained  at 
a  certain  stage  in  the  digestion  of  proteins  by  pancreatic  juice,  but 
nothing  was  known  about  its  constitution  until  Hopkins  succeeded 
in  isolating  it  by  precipitation  with  mercuric  sulphate  dissolved 
in  5  per  cent,  sulphuric  acid.  Cystine  is  also  precipitated  by  this 
reagent,  but  comes  down  with  a  less  concentration  of  the  salt  than 
tryptophane,  so  that  it  is  possible  to  separate  the  two  substances 
by  a  species  of  fractional  precipitation.  Tryptophane  can  be  isolated 
by  decomposing  the  mercury  salt  with  sulphuretted  hydrogen,  and 
is  obtained  in  a  crystallised  form.  On  distillation  it  gives  an  abundant 
yield  of  indol  and  skatol,  bodies  also  obtained  during  the  putrefaction 
of  proteins.     Tryptophane  itself  is  indol  amino-propionic  acid  : 


C.CH2CHNH2.COOH 


^6^4. 


CH 


NH 


C.     AMINO-ACIDS  OF   HETEROCYCLIC  COMPOUNDS 
Three  of  the  disintegi-ation  products  of  proteins  can  be  grouped  in 
this  class.     Two  of  them  contain  the  pyrrol  ring,  namely,  proline  and 
oxyproline. 

PROLINE,   which   was  first   isolated    by  Fischer,   is  a-pyrrohdin 
carboxylic  acid  and  has  the  formula 

CH2 — CH2  / 

I  I 

CH2    CH.COOH 

\/ 
NH 


THE  PROTEINS  95 

OXYPROLINE  is  the  oxy- derivative  of  this  body  and  has  the  formula 
CjligNO-j,  tlie  exact  position  of  the  oxy-irroup  fiaving  not  yet  been 
determined.  Doubts  have  been  expressed  whether  the  pyrrol  group  is 
present  as  such  in  the  protein  molecule,  or  whether  proline,  for  example, 
is  not  formed  by  the  closing  of  an  open  chain  of  a  compound  belonging 
to  the  amino-acids  in  the  fatty  series.  Thus  from  an  oxy-amino- 
valerianic  acid  CHgOH .  CHg .  CH2 .  CH .  NHg .  COOH  we  can  by  dehy- 
dration make  the  compound  CH2CH2.C.H2.CH.COOH,  which  will  be 


NH 

seen  to  be  identical  with  that  given  for  proline. 

The  third  member  of  this  group  contains  the  iniinuzut  ring  : 

CH-NH 

II  /CH 

C       ~  N 

and  is  known  as  HISTIDINE.     Its  structural  formula  is  as  follows 

CH— NH. 


^CH 


C N^ 

CH2.CH.NH2.COOH 

i.e.  it  is  iminazol  a-amino-propionic  acid  or  iminazol  alanine.  Since 
it  occurs  in  the  phosphotungstic  precipitate  from  the  products  of  acid 
disintegration  of  proteins  and  contains  six  carbon  atoms,  it  was 
formerly  classified  with  lysine  and  arginine  as  a  hexone  base. 

D.  SULPHUR-CONTAINING  AMINO-ACIDS 
Sulphur  forms  an  integral  part  of  the  molecule  of  all  classes  of 
proteins  except  protamines.  In  some  substances  allied  to  proteins, 
such  as  keratin,  it  may  occur  to  the  extent  of  3  per  cent.  On  boil- 
ing ])r()tcins  with  caustic  potash  or  soda,  a  portion  of  the  sul])hur 
is  split  off  to  form  a  sulphide,  which  gives  a  black  precipitate  on 
addition  of  copper  salts.  On  this  account  it  was  formerly  thouuht 
that  the  sulphur  must  be  present  in  two  forms,  the  oxidised  and  the 
unoxidised,  in  the  protein  molecule.  Recent  investigation  has  shown, 
however,  that  j)ractically  the  whole  of  the  sulj)hur  is  present  in  the 
form  of  CYSTINE,  and  that  this  body  on  boiling  with  alkaline  solutions 
gives  up  only  a  little  more  than  half  its  content  in  sulphm:. 

This  substance,  which  has  been  known  for  many  years  as  the 
chief  constituent  of  a  rare  form  of  urinary  calculus  and  as  occurring  m 
the  urine  in  certain  cases  of  disordered  metabolism,  is  again  a  deriva- 


96  PHYSIOLOGY 

tive  of    the   three-carbon    propionic    acid.     On   reduction  it  gives  a 
body  known  as  cysteine,  which  is  a-amino-thiopropionic  acid. 

CHgSH 
CH.NH2 

COOH 

Cystine  itself  is  compounded  of  two  cysteine  molecules  joined  together 
by  their  sulphur  atoms  and  has  the  formula 

CH2 — S — S— CH2 

CH.NH2        CH.NHo 

I  I 

COOH  COOH 

E.  OTHER  CONSTITUENTS  OF  THE  PROTEIN  MOLECULE 
When  we  add  together  the  total  amino- acids  obtainable  by  the 
acid  disintegration  of  any  given  protein,  a  considerable  proportion  of 
the  original  protein  remains  unaccounted  for.  This  remainder  must 
have  a  gxeater  content  in  hydrogen  and  oxygen  than  the  amino- acids 
enumerated  above,  and  it  has  been  suggested  that  among  the  missing 
unascertained  constituents  of  proteins  may  be  oxyamino-acids,  of 
which  serine  would  form  one  of  the  lowest  members.  The  isolation  of 
such  substances  would  present  considerable  interest,  in  that  it  would 
supply  the  intermediate  stages  between  the  constituent  groups  of  the 
protein  molecule  and  the  carbohydrates,  the  first  product  of  assimilation 
by  living  organisms.  Only  one  such  intermediate  body  has  so  far 
been  isolated,  namely,  glucosamine,  an  amino-derivative  of  glucose. 
It  was  first  shown  by  Pavy  that  from  the  products  of  disintegration  of 
a  protein  such  as  egg-white  it  was  possible  to  obtain  a  reducing  sub- 
stance and  to  isolate  an  osazone  resembling  in  its  characters  those 
derived  from  the  sugars.  Since  then  various  observers  have  shown 
that  this  reducing  substance  is  most  probably  glucosamine  : 

CH2OH 

I 
(CHOH), 

I 
CH.NH2 

CHO 

Although   this   substance    may   be    obtained    from    crystallised   egg 
albumin    or    crystallised    serum   albumin,    authorities    are   not   yet 


THE  PROTEINS  07 

convinced  that  it  l"ornis  an  integral  part  of  these  proteins.  Botli  egg- 
white  and  serum  contain  proteins  belonging  to  the  class  of  mucins, 
ovomucoid  and  serum  mucoid,  each  of  which  yields  on  acid  hydrolysis 
from  16  to  30  per  cent,  glucosamine.  Since  various  observers  have 
obtained  results  varying  from  1  to  10  per  cent,  glucosamine  for  crystal- 
lised egg  albumin,  it  seems  possible  that  in  every  case  the  crystals 
carried  down  with  them  some  of  the  carbohydrate-rich  mucoid,  and 
that  the  varying  results  were  due  to  the  different  amounts  of  mucoid 
present  in  the  crystals.  By  our  ordinary  methods  it  is  impossible  to 
prepare  a  specimen  of  either  egg  albumin  or  serum  albumin  which 
is  entirely  free  from  this  amino-derivative  of  carbohydrate. 

Connected  with  this  group  of  proteins  may  be  reckoned  the  diamino- 
trioxydodecoic  acid  already  mentioned  as  occurring  among  the  dis- 
integration products  of  proteins. 


THE    BUILDING    UP   OF    THE    PROTEIN   MOLECULE 

By  simple  hydrolysis  the  protein  molecule  may  be  broken  down 
into  a  large  number  of  amino- acids.  Analyses  of  various  proteins 
show  that  these  amino-acids  are  present  in  different  proportions  in  the 
individual  proteins,  so  that  in  many  cases  a  large  number  of  identical 
amino-acid  gToups  must  be  present  in  the  protein  molecule  with  smaller 
numbers  of  other  groups.  In  endeavom'ing  to  form  an  idea  of  the 
manner  in  which  the  amino-acids  can  be  linked  together  into  one  gigantic 
molecule,  Hofmeister  first  put  forward  the  idea  that  the  hnkage  follows 
the  general  formula  : 

— CH2— NH— CO— 
or         — NH— CH2— CO— NH— 

This  theory  of  the  constitution  of  proteins  was  based  on  the  fact  that 
a  similar  grouping  was  known  to  occur  in  leucinimide,  obtained  by 
the  condensation  of  two  molecules  of  leucine, 

C4H9 

NH  CO 

1  I 

CO  NH 

\ch/ 

and  also  by  the  fact  that  only  a  small  proportion  of  the  NH,  groups 
present  in  the  separated  amino-acids  exist  free  in  the  protein  molecule. 

7 


98  PHYSIOLOGY 

By  the  action  of  nitrous  acid  the  terminal  XHo  groups  are  split  off  and 
replaced  by  OH.  When  proteins  are  treated  with  nitrous  acid  only  a 
small  proportion  of  the  total  nitrogen  is  split  off  in  this  way.  The 
linking  of  the  amino  groups  must  therefore  take  place  by  means  of  the 
nitrogen,  i.e.  by  XH  groups.  Synthetic  experiments  have  fully  con- 
firmed this  hypothesis.  In  1883  Curtius  obtained  a  substance  giving 
the  biuret  reaction,  the  so-called  '  biuret  base.'  by  the  spontaneous 
polymerisation  of  glycocoll  ester.  This  base  has  been  shown  by  recent 
researches  to  consist  of  four  glycine  molecules  arranged  together  in 
an  open  chain.  The  clue  to  the  structure  of  this  base  was  given  by 
Fischer,  who  has  devised  a  number  of  ingenious  methods  for  combining 
together  amino-acids  of  any  character  and  in  any  number.  Thus  from 
two  molecules  of  glycine  we  may  obtain  the  compound  glycyl  glycine, 
as  follows  : 

XH2 .  CH2 .  COOH  -f  HXH .  CH2 .  COOH  —  H,0  - 
NH2 .  CH2.CO.XH.CH2 .  COOH 

This  may  be  prepared  in  various  ways.  In  one  method  glycine  is  converted 
into  its  ester  CH2.XH2.CO.OCH3.  In  a  waterj-  solution  this  undergoes  spon- 
taneous conversion  into  gl\-cine  anhydride,  which  belongs  to  the  class  of  bodies 
kno«-n  as  diketopiperazins,  as  follows  : 

/CHo— CO 
2XHo.CH,CO.OCH3  =  2CH3OH   -1-  XH'  XT! 

methyl  alcohol  QO—CE./ 

On  treating  this  with  dilute  alkali  it  takes  up  water,  splitting  in  the  situation 
of  the  dotted  line  and  forming  glycyl  glycine.  XHoCHoCO.XH.CHoCOOH. 

More  general  methods  have  been  devised  by  Fischer  for  the  same  purpose, 
depending  on  the  use  of  the  halogen  acyl  chlorides. 

Thus  chloracetjichloride  and  alanine  jneld  chloracetalanine  : 

CI .  CH, .  COCI  +  XTI, .  CH( CH3 ) .  COOH  = 
CI.CH2.CO  -  XH.CH(CH3)C00H  +  HCl. 

By  the  subsequent  action  of  ammonia,  the  halogen  group  is  replaced  by  the 
amino  group,  and  a  dipeptide  results  : 

CI.CH2.CO  -  XH.CH(CH3)C00H  +  2XH3  = 
XHo.CHoCO  -  XH.CH(CH3)C00H  -i-  XH4CI. 

Different  halogen  acyl  chlorides  are  u.sed  for  introducing  the  various  amino- 
acid  radicals,  e.g.  chloracetylchloride  for  glycyl,  n-bromopropionylchloride  for 
alan}-l,  &c. 

By  various  such  methods  Fischer  has  succeeded  in  combining 
compounds  containing  as  many  as  eighteen  amino-acids,  e.g.  alanyl 
leucine,  glycyl  tyrosine,  dialanyl  cystine,  dileucyl  cystine,  leucyl 
pentaglycyl  glycine,  and  so  on.  The  last  named  would  be  built  up 
out  of  one  molecule  of  leucine  and  six  molecules  of  glycine.  These 
compounds  have  been  designated  by  Fischer  as  polypeptides,  to  sig- 
nify their  close  connection  with  the  peptones  produced  by  the  agency 


THE  PROTEIXS  99 

of  digestive  ferments  on  the  proteins.  He  distinguishes  di-.  tri-, 
tetra-,  &c.,  peptides  according  to  the  number  of  individual  aniino-acids 
taking  part  in  the  formation  of  the  compound.  The  polypeptides 
resemble  in  all  respects  the  peptones.  Most  of  them,  even  if  derived 
from  relatively  insoluble  amino-acids,  are  soluble  in  water,  insoluble 
in  absolute  alcohol.  They  dissolve  in  mineral  acids  and  in  alkahes 
with  the  formation  of  salts,  thus  resembling  in  their  behaviour  the 
amino-acids.  They  have  a  bitter  taste,  although  the  amino-acids 
from  which  they  are  formed  have  a  shghtly  sweet  taste,  in  this  way 
again  resembling  the  natural  peptones.  The  higher  members  of  the 
series  give  certain  reactions,  such  as  the  biuret  reaction,  which  are 
regarded  as  characteristic  of  peptones,  and  Uke  the  latter  are  pre- 
cipitated by  phosphotungstic  acid.  Their  behaviour  with  trypsin 
depends  on  the  optical  beha>-iour  of  the  amino-acids  from  which  they 
are  formed.  If  synthetised  from  the  amino-acids  identical  with  those 
occurring  in  the  disintegration  of  natural  proteins,  they  resemble  the 
peptones  in  undergoing  hydrolysis  and  disintegration  into  their 
constituent  amino-acids.  Trypsin,  however,  has  no  influence  on  poly- 
peptides compounded  of  the  inactive  amino-acids,  or  of  the  amino- 
acids  which  are  the  optical  opposites  of  those  which  form  the 
constituents  of  normal  proteins.  Though  most  of  the  amino-acids 
which  occur  naturally  are  laevo-rotatory,  the  poh'peptides  formed  from 
them  are  generally  strongly  dextro-rotatory. 

Thus  in  the  building  up  of  the  protein  molecule  there  is  an  almost 
indefinite  couphng  up  of  numerous  amino-acid  groups,  the  connecting 
element  in  each  case  being  the  nitrogen.  Of  the  two  or  more  optical 
isomers  possible  of  each  amino-acid  containing  more  than  two  carbon 
atoms,  only  one  is  made  use  of  for  this  purpose.  A  still  further 
flexibility  in  its  reactions  to  its  environment  is  conferred  on  the  protein 
molecule  by  changes  occurring  with  great  readiness  in  the  intra- 
molecular grouping  of  its  constituent  atoms.  Thus,  if  we  take  the 
simplest  member  of  the  class  of  polypeptides,  glycyl  glycine,  four 
structural  formulae  are  possible,  namely  : 


(1) 

XHXH/l)  -  XH.(H,.COOH 

{^) 

XH.CH,.C() 

1        "      >o 

CO.CH2.XH3 

(3) 

XH..CH2.C(0H)  =  X.CH2.COOH 

(4) 

X.CH2.CO 

II  0 

C(OH)CH2.XTl3 

(2)  and  (4)  being  the  intramolecular  form  of  the  formulae  (1)  and  (3). 


100 


PHYSIOLOGY 


(3)  and  (4)  are  soni.etimes  spoken  of  as  the  enolic  form.  If  we  con- 
sider that  perhaps  some  hundred  of  the  amino-acid  groups  may  go  to 
making  up  a  single  protein  molecule,  it  is  possible  to  form  some  con- 
ception of  the  enormous  variability  in  reaction  possible  to  such  a 
compound. 

THE  CONSTITUTION  OF  DIFFERENT  PROTEINS 

All  the  proximate  constituents  of  proteins,  so  far  as  we  know, 
are  amino- acids.  Of  these  the  following  have  been  isolated,  namely, 
glycine,  alanine,  amino-valerianic  acid,  leucine,  isoleucine,  proline, 
oxyproline,  serine,  phenyl  alanine,  glutamic  acid,  aspartic  acid, 
tyrosine,  tryptophane,  cystine,  lysine,  histidine,  arginine,  and  '  di- 
amino-trioxydodecoic  '  acid. 

The  question  now  arises  whether  all  the  different  varieties  of  pro- 
tein owe  their  peculiarities  to  the  presence  of  different  amino-acids  or 
whether  the  greater  number  of  the  amino-acids  above  mentioned  are 
present  in  all  proteins,  the  differences  between  the  latter  being  deter- 
mined by  differences  in  the  arrangement  and  relative  amounts  of  their 
proximate  constituents.  A  large  number*  of  analyses  of  different 
proteins  have  been  made  by  Abderhalden,  Osborne,  and  others, 
utilising  the  methods  for  the  isolation  of  amino-acids  devised  by 
Fischer.  The  constitution  of  some  representative  proteins  as 
determined  in  this  way  are  given  in  the  following  Table  : 


3    S 

V2     « 

Eclestin 

(hemp 

seeds) 

3 

c 

M 
O 

C 

c 
3 

o 

3 

£ 

'a, 

Tfl 

3 

— 

Keratin 
(from  horse 
hair) 

Glycine 

0 

0 

3-8 

0-9 

0 

0 

0 

16-5 

4-7 

Alanine 

2-7 

8-1 

3-6 

2-7 

1-5 

4-2 

— 

— 

0-8 

1-5 

Serine 

0-fi 

— 

0-33 

0-12 

0-5 

0-6 

7-8 

— 

0-4 

()•(•) 

Amino  -  valeri  - 

anic  acid 

— 

— 

present 

0-3 

7-2 

• — 

4-3 

— 

10 

0-9 

Leucine 

20-0 

71 

20-9 

6-0 

9-35 

29-0 

0 

— 

21 

7-1 

Proline 

10 

2-25 

1-7 

2-4 

0-70 

2-3 

11-0 

— 

5-2 

3-4 

Oxyproline 

— 

— 

2() 

— 

0-23 

1-0 

— 

— 

30 

— 

Glutamic  acid 

7-7 

8-0 

(5-3 

36-,5 

1.5-55 

1-7 

— 

— 

0-88 

3-7 

Aspartic  acid 

.31 

1-.5 

4  •.'5 

1-3 

1-39 

4-4 

— 

— 

0-5() 

0-3 

PlK'nylalaiiine     . 

.31 

4-4 

2-4 

2-G 

3-2 

4-2 

— 

— 

0-4 

0 

Tyrosine     . 

2-1 

11 

21 

2-4 

4-5 

1-5 

— 

— 

0 

3-2 

Tryptophane 

present 

present 

present 

10 

1-50 

present 

■ — 

— 

0 

— 

Cystine 

2-3 

0-2 

0-2.5 

0-45 

1 

0-3 

— 

^ 

— 

ov.  lO'i 

Lysine 

— 

2-1.5 

1-0 

0 

5-95 

4-3 

0 

12-0 

2-75 

1-1 

Arginine     . 

— 

214 

11-7 

3-4 

3-81 

5-4 

87-4 

58-2 

7-62 

4-5 

Histidine   . 

11 

1-7 

2-5 

110 

0 

12-9 

0-4 

0-6 

These  results  show  that  all  the  proteins  contain  a  very  considerable 


THE  PR0TEIN8  101 

proportion  of  the  total  number  of  aniino-afids  wliich  have  as  yet  been 
isolated  from  acid  digests  of  proteins.  The  differences  in  various 
proteins  cannot  therefore  be  determined  by  qualitative  differences 
in  their  constituent  molecules,  but  must  depend  on  the  relative  amounts 
of  the  amino-acids  which  are  present  and  on  their  arrangement  in 
the  whole  molecule.  As  regards  relative  amounts  of  amino-acids  we 
find  very  striking  differences.  Thus,  glutamic  acid,  which  forms  8  per 
cent,  of  egg  albiunin  and  only  1-7  jjer  cent,  of  globin  (derived  from 
haemoglobin),  amounts  to  31-5  per  cent,  in  gliadin,  the  protein  extracted 
from  wheat  flour.  Striking  differences  are  also  noticeable  in  the 
relative  proportions  of  the  diamino-acids  and  bases,  the  so-called  hexone 
bases.  Whereas  in  casein  they  form  about  12  per  cent,  of  the  total 
molecule,  in  globin  they  form  about  20  per  cent.,  and  in  the  prota- 
mines, salmine  and  sturine,  about  85  per  ceiit.  of  the  total  molecule 
consists  of  these  bodies.  On  this  account  the  two  last-named  bodies 
have  a  strongly  basic  character.  From  these  figures  it  is  evident  also 
that  certain  of  the  amino-acids  must  occur  many  times  over  in  the  pro- 
tein molecule.  Thus  in  globin,  if  we  assume  the  presence  of  one 
tyrosine  molecule,  there  must  be  at  least  thirty-two  leucine  and  ten 
histidine  molecules.  On  these  data  the  molecular  weight  of  haemo- 
globin would  come  out  at  about  14.000,  a  figure  which  agrees  with  that 
derived  from  a  study  of  the  amounts  of  sulphur  and  iron  respectively 
in  its  molecule. 

THE    DISTRIBUTION    OF    NITROGEN    IN    THE   PROTEIN 

MOLECULE 
Attempts  have  been  made  to  differentiate  among  the  proteins 
by  a  method  which,  while  less  laborious  than  the  isolation  and  recogni- 
tion of  the  individual  amino-acids,  may  yet  throw  some  light  on  the 
manner  in  which  the  nitrogen  is  combined  within  the  molecule,  and  on 
the  relative  amounts  of  the  different  classes  of  nitrogen  groups  which 
may  be  present.  One  method,  which  was  devised  by  Hausmann,  is 
carried  out  as  follows.  One  gramme  of  the  protein  is  dissociated 
by  boiling  with  strong  hydrochloric  acid.  The  nitrogen,  which  has 
been  split  off  as  ammonia  and  is  present  in  the  solution  as  ammonium 
chloride,  is  then  distilled  off  with  magnesia  and  received  into  deci- 
normal  acid,  where  its  amount  can  be  determined  by  titration.  This 
nitrogen  is  variously  designated  as  amide  nitrogen,  ammonia  nitrogen, 
or  easily  displaceable  nitrogen.  The  remaining  fluid,  freed  from 
ammonia,  is  precipitated  with  phosphotungstic  acid.  By  this  means 
all  the  diamino-acids  and  bases  are  thrown  down.  The  nitrogen  in 
the  precipitate  is  determined  by  Kjeldahl's  method  and  is  called 
diamino-  or  basic  nitrogen.  In  the  remaining  fluid,  which  contains 
mono-amino-acids,  the   total  nitrogen,  the   mono-amino-nitrogen,  is 


102 


PHYSIOLOGY 

Table  I. 


Group 

Protein 

Source 

X  per 

cent 

Amide 
X 

Amino 

Basic 
X 

Humiu 
X 

Protamines 

(  Salmine 
(Sturine 

Salmon -roe 
Stiu-geon-roe 

— 

() 
0 

87-8 
83-7 

Histones 

Histone 

Thymus 

— 

3-3 

38-7 

Albumins 

and 

Ovalbumin 

Egg-white 

15-51 

8-64 

68-13 

21-27 

1-87 

pliospho- 

Caseinogen 

Milk 

15-62 

10-36 

66-00 

22-34 

1-34 

proteins 

' 

Globulins 

1  Globulin 

Wheat 

18-39 

7-72 

53-40 

37-10 

1-52 

(Edestin 

Hemp  seed 

18-64 

10-08 

57-83 

31-70 

0-64 

Alcohol - 
soluble 
proteins 

1  Zein 

Maize 

16-13 

18-40 

77-56 

3-03 

0-99 

1  Gliadin 

Wheat  and  rxt 

17-66 

23-78 

70-27 

5-54 

0-79 

Prot- 

Witte's 

All^umoses 

albuinose 
Hetero- 

peptone 
Witte's 

— 

714 

68-17 

25-42 

— 

albumose 

peptone 

— 

6-45 

57-4 

38-93 

Table  II. — -Distribution  of  the  Nitrogen  in  Various  Proteins 

(Van  Slyke) 


Gliadin 

Edestin 

Hair 
(dog) 

Gelatin 

Fibrin 

Hsemo- 
cyanin 

Ox  haemo- 
globin 

Ammonia  N    . 

25-52 

9-99 

10-05 

2-25 

8-32 

5-95 

5-24 

Melanine  N 

0-86 

1-98 

7-42 

0-07 

3-17 

1-65 

3-60 

Cystine  N 

1-25 

1-49 

6-60 

0 

0-99 

0-80 

0  V 

Arginine  N 

5-71 

27-05 

15-33 

14-70 

13-86 

15-73 

7-70 

Histidine  N 

5-20 

5-75 

3-48 

4-48 

4-83 

13-23 

12-70 

Lysine  N 

0-75 

3-86 

5-37 

6-32 

11-51 

8-49 

10-90 

Amino    N    of    the 

filtrate 

51-98 

47-55 

47-50 

56-30 

54-30 

51-30 

57-00 

Xon-amino  X  of  the 

filtrate       (proline, 

oxyproline,            J 

tryptophane) 

8-50 

1-70 

3- 10 

lJ-90 

2-70 

3-80 

2-90 

Sum 

99-77 

99-37 

99-85 

99-02 

99-58 

l(X)-95 

100-00 

determined  by  Kjeldahl's  method.  Table  I.  (above)  gives  some 
of  the  results  obtained  in  this  manner,  and  shows  that  there  are  con- 
siderable  differences   in   the   distribution   of   the   different   kinds   of 


THE  PROTEINS  103 

nitrogen  amonj^  the  various  classes  of  proteins.  The  method  is, 
however,  only  a  rough  one  as  compared  with  the  separation  of  the 
individual  amino-acids. 

An  improved  means  of  determining  the  distribution  of  nitrogen 
in  the  protein  molecule  has  been  devised  by  Van  Slyke.  Some  of  his 
results  are  gi\'en  in  Table  11..  p.  102. 


TESTS    FOR    PROTEIN 
A.     COLOUR   REACTIONS   OF  THE   PROTEINS 

These  are  of  importance  since  in  many  cases  they  are  an 
indication  of  the  nature  of  the  groups  present  in  the  protein 
molecule. 

(1)  THE  BIURET  REACTION.  When  a  solution  of  a  protein 
is  made  strongly  alkaline  with  caustic  potash  or  soda,  and  dilute  copper 
sulphate  added  drop  by  drop,  a  colour  varying  from  pink  to  violet 
is  produced.  In  the  case  of  the  proteoses  and  peptones  (the  hydrated 
proteins)  the  colour  is  pink  ;  in  the  case  of  the  coagulable  proteins, 
violet.  According  to  Schiflt  this  colour  is  given  by  all  compounds 
containing  the  following  groups  : 

CO.NH2 

NH<( 

CO.NH2 

CO.NH2 

ch/ 

^CO.NH., 
CO— NH, 

CO— NH2 

and  the  group 

I  I 

(NH2)C— CO— NH-C 


We  have  already  seen  that  this  grouping  is  typical  of  the  protein 
molecule. 

(2)  THE  XANTHO-PROTEIC  REACTICN.  On  adding  strong 
nitric  acid  to  a  solution  of  protein  and  l)oiling,  a  yellow  colour  is  pro- 
duced which  turns  to  a  deep  orange  when  excess  of  caustic  alkali  or 
ammonia  is  added.  The  production  of  this  reaction  points  to  the 
existence  of  benzene  derivatives  in  the  protein  molecule,  and  it  is 
therefore  a  general  test  for  the  presence  of  aromatic  gioups. 


104  PHYSIOLOGY 

(3)  MILLON'S  REACTION.  Millon's  reagent  is  a  solution  of 
mercuric  nitrate  in  water  containing  free  nitrous  acid.  On  adding  a 
few  drops  of  this  to  a  protein  solution  a  white  precipitate  is  produced 
which  turns  a  brick-red  colour  on  boiling.  It  depends  on  the  presence 
in  the  protein  of  a  hydroxy- derivative  of  benzene,  and  is  determined 
in  the  protein  by  the  tyrosine,  which  is  oxyphenylalanine. 

(4)  SULPHUR  REACTION.  On  warming  a  solution  of  protein 
with  caustic  soda  in  the  presence  of  lead  acetate  a  black  colour  is 
produced  owing  to  the  precipitation  of  lead  sulphide.  The  depth  of 
coloration  gives  a  rough  indication  of  the  amount  of  sulphur  in  the 
protein  under  investigation. 

(.5)  THE  HOPKINS-ADAMKIEWICZ  REACTION.  It  was  stated 
by  Adamkiewicz  that  on  the  addition  of  acetic  acid  and  concentrated 
sulphuric  acid  to  protein,  a  violet  colour  was  produced.  Hopkins 
and  Cole  showed  that  the  success  of  this  reaction  depended  on  the 
presence  of  glyoxylic  acid  CHO.COOH  as  an  impurity  in  the  acetic 
acid  used.     The  test  is  therefore  performed  now  as  follows  : 

Glyoxylic  acid  is  prepared  by  the  action  of  sodium  amalgam 
on  a  solution  of  oxalic  acid.  A  few  drops  of  this  solution  are  added  to 
the  solution  of  protein,  and  strong  sulphuric  acid  poured  down  the 
side  of  the  tube.  A  bluish-violet  colour  is  produced  at  the  junction 
of  the  two  fluids.  This  reaction  is  due  to  the  presence  in  the  protein 
of  tryptophane. 

The  so-caUed  Liebermann's  reaction  has  been  shown  by  Cole  to  be  essen- 
tially ^  modification  of  the  above,  and  is  due  also  to  the  presence  of  tryptophane. 
In  this  test  the  protein  is  precipitated  by  alcohol,  washed  with  ether,  and  heated 
with  concentrated  hydrochloric  acid,  when  a  blue  colour  is  produced,  glyoxylic 
acid  being  derived  from  the  alcohol  and  ether. 

(6)  REACTIONS  INDICATING  THE  PRESENCE  OF  CARBO- 
HYDRATES. Mohsch's  test  is  applied  as  follows.  A  few  drops  of 
alcoholic  solution  of  a-naphthol  and  then  strong  sulphuric  acid  are 
added  to  a  protein  solution.  A  violet  colour  is  produced,  which  on 
addition  of  alcohol,  ether,  or  potash  turns  yellow.  The  reaction  is 
determined  by  the  presence,  either  as  an  impurity  or  a  constituent 
part  of  the  molecule,  of  a  carbohydrate  radical  which,  under  the 
influence  of  strong  sulphuric  acid,  is  converted  into  furfurol.  The 
furfurol  gives  the  colour  reaction  with  the  a-naphthol. 

Another  test  for  the  carbohydrate  radical  is  the  orcin  reaction. 
A  small  quantity  of  the  dried  albumin  is  added  to  5  c.c.  of  fuming 
hydrochloric  acid,  and  the  mixture  is  then  warmed.  When  the 
albumin  is  nearly  all  dissolved  a  little  solid  orcin  is  added  on  the  point 
of  a  knife,  and  then  a  drop  of  ferric  chloride  solution.  After  warming 
this  mixture  for  some  minutes  a  green  colour  is  produced  which  is 
soluble  in  amyl  alcohol  and  gives  a  definite  absorption  spectrum. 


THE  PROTEINS  105 

B.     METALLIC  SALTS 
The  following  metallic  salts  form  double  insoluble  compounds  witli 
proteins,  and  therefore  cause  a  double  precipitation  when  added  to 
solutions  of  these  bodies :  fenic  chloride,  copper  sulphate,  merc\u:ic 
chloride,  lead  acetate,  zinc  acetate. 

C.  ALKALOIDAL  REACTIONS 
Proteins,  like  the  polypeptides  and  the  amino-acids  of  which  they 
are  composed,  may  function  either  as  weak  acids  or  as  weak  bases, 
according  as  they  are  treated  with  bases  or  acid  radicals  respectively. 
In  the  presence  of  strong  acids,  therefore,  proteins  act  like  organic 
bases,  and  are  thrown  do\\ai  in  an  insoluble  form  by  the  various  alka- 
loidal  precipitants.  With  certain  proteins,  such  as  the  protamines, 
where  there  is  a  preponderance  of  basic  groups,  it  is  not  necessary  to 
add  mineral  acid  in  order  to  ensure  the  precipitation.  The  following 
are  the  principal  alkaloidal  precipitants  which  may  be  employed  : 

(a)  Phosphotungstic  acid. 
{b)  Phosphomolybdic  acid. 
{(■)  Tannic  acid. 

(d)  Potassium  mercuric  iodide. 

(e)  Acetic  acid  and  potassium  ferrocyanide. 

(/)  Trichloracetic  acid.     (In  order  to  precipitate  all  the  coagulable 
proteins  from  a  solution  it  is  treated  with  an  equal  volume 
of  10  per  cent,  trichloracetic  acid,  well  shaken  and  filtered.) 
(g)  Metaphosphoric  acid. 
{h)  Salicyl-sulphonic  acid. 

These  two  latter  are  generally  employed  in  a  5  per  cent, 
solution. 
(i)  Picric  acid. 

A  mixture  of  picric  and  citric  acids  is  largely  employed, 
under  the  name  of  Esbach's  reagent,  as  a  precipitant  for 
coagulable  proteins  in  the  urine. 

D.     TESTS  DEPENDING   ON  THE  COLLOIDAL  CHARACTER 
OF  THE  PROTEIN 

(1)  HEAT  COAGULATION.  On  boihng  proteins  in  a  very 
slightly  acid  solution  some  are  coagulated  and  form  an  insoluble  white 
precipitate.  This  test  is  applicable  to  albumins,  globulins,  and 
under  certain  conditions  to  the  derived  albumins.  In  order  that 
the  separation  of  protein  in  this  way  may  be  comjilete  it  is  necessary 
to  ])rovide  for  the  presence  of  neutral  salts  and  also  for  the  maintenance 
of  a  slight  acidity.     The  best  method  of  carrying  out  this  test,  therefore, 


106  PHYSIOLOGY 

is  to  boil  tlie  protein  in  slightly  alkaline  or  neutral  solution  after  the 
addition  of  2-5  per  cent,  of  sodium  chloride  or  sodium  sulphate. 
While  the  solution  is  in  active  ebullition  1  per  cent,  acetic  acid  is 
added  drop  by  drop  until  the  reaction  is  just  acid  to  litmus.  By  this 
means  a  nearly  perfect  separation  of  all  the  coagulable  proteins  may 
be  effected. 

(2)  HELLER'S  TEST.  On  pouring  a  solution  of  protein  carefully 
down  the  side  of  a  test-tube  containing  strong  nitric  acid  so  as  to 
form  a  layer  on  the  top,,  a  white  layer  of  coagulated  protein  is  pro- 
duced at  the  junction  of  the  two  fluids.  A  similar  coagulative  effect  is 
produced  by  other  strong  mineral  acids. 

(3)  PRECIPITATION  BY  NEUTRAL  SALTS.  On  addition  of  a 
neutral  salt  in  excess  to  a  colloidal  solution  the  relation  between 
the  solvent  and  the  particles  which  are  in  suspension  or  pseudo-solution 
are  altered.  It  is  therefore  possible  in  man}'  cases  by  the  addition  of 
neutral  salts  to  separate  out  the  dissolved  colloid  without  otherwise 
altering  its  characters  in  any  way,  so  that,  on  collecting  the  precipitate 
and  separating  the  salt  carried  down  with  it,  it  can  be  dissolved  again 
by  adding  water.  Some  classes  of  proteins  can  be  salted  out  very 
readily,  while  others  require  a  much  higher  concentration  of  salt 
before  they  are  precipitated. 

The  salts  which  are  generally  employed  for  salting  out  proteins 
have  been  divided  by  Schryver  into  three  classes  : 

Class  I. 

Sodium  chloride. 
Sodium  sulphate. 
Sodium  acetate. 
Sodium  nitrate. 
Magnesium  sulphate. 

Class  II. 

Potassium  acetate. 
Calcium  chloride. 
Calcium  nitrate. 

The  two  calcium  salts  are,  however,  rarely  employed,  as  they  tend 
to  render  the  precipitated  protein  insoluble. 

Class  III. 

Ammonium  sulphate. 
Zinc  sulphate. 

The  salts  of  the  first  class  require  much  higher  concentration 
for  the  precipitation  of  the  albumins  than  those  of  the  second,  and 
these  than  those  of  the  third.     Since  the  degree  of  concentration  of  any 


THE  PKOTELXS  «  107 

salt  necessary  for  the  precipitation  of  any  particular  protein  is  charac- 
teristic for  this  body,  it  is  possible  to  employ  a  fractional  process  of 
salt  precipitation  in  order  to  separate  mixtures  of  proteins  into  their 
components.  Owing,  however,  to  the  tenacity  with  which  different 
colloids  adhere  to  one  another  it  is  difficult,  even  after  many  repetitions 
of  the  process  of  fractional  salting  out,  to  obtain  products  which  can 
be  regarded  as  free  from  admixture.  For  the  purpose  of  fractional 
precipitation  the  salts  most  frequently  employed  are  those  of  the  third 
class,  namely,  ammonium  sulphate  and  zinc  sulphate.  We  shall 
have  to  deal  witli  results  obtained  by  this  method  when  treating  of 
the  separation  of  albumoses  and  peptones.  The  precipitability  of 
different  proteins  with  neutral  salts  serves  also  as  the  basis  of  the 
ordinary  classification  of  these  bodies. 

THE    CLASSIFICATION    OF    PROTEINS 

It  is  possible  that  in  the  future,  when  we  kno^^'  all  the  disintegra- 
tion products  of  the  various  proteins  and  the  manner  in  which  they 
are  arranged  in  the  molecule,  the  classification  of  these  bodies  will 
be  based  on  their  constitution.  At  the  present  time  it  is  obviously 
impossible  to  admit  any  classification  on  such  a  basis,  since  the  neces- 
sary knowledge  is  wanting,  and  we  have  therefore  to  make  use  of  a 
purely  artificial  classification,  such  as  that  adopted  by  the  Chemical 
and  Physiological  Societies  in  1907,  based  chiefly  on  the  solubilities 
of  the  various  proteins  in  water  and  salt  solutions.  We  shall  here 
only  indicate  the  characters  of  the  main  groups  into  which  proteins 
are  conventionally  divided,  and  leave  the  closer  study  of  the  individual 
proteins  to  be  dealt  with  in  connection  with  the  organs  or  tissues  in 
which  they  occur. 

(1)  THE  PROTAMINES.  These  occur  in  the  body  only  in  com- 
bination with  other  groups.  They  are  obtained  from  the  ripe  sperma- 
tozoa of  certain  fishes,  where  they  occur  in  combination  with  nucleic 
acid.  They  are  characterised  by  the  very  large  amount  of  bases 
contained  in  their  molecule,  amounting  to  85  per  cent,  of  the  total 
substance.  It  was  formerly  thought  by  Kossel  that  the  protamines 
contained  only  diamino-acids  and  bases,  but  it  has  been  shown  later 
that  a  small  proportion  of  mono-amino-acids  may  also  be  obtained 
from  their  disintegration  {v.  Table,  p.  100).  On  account  of  their 
constitution  they  jiossess  strongly  basic  characters  and  form  well- 
marked  salts,  e.g.  sul])hates  and  chlorides,  as  well  as  double  salts  with 
platinum  chloride.  They  contain  no  sulphur  and  do  not  coagulate 
on  heating. 

(2)  HISTONES.  Tin's  class  of  j)n)teins.  like  tlic  )in)t;<iniu«\s.  only 
occurs  in  combination  with  other  grouj)s,  such,  for  instance,  as  nuclein 
and  ha)matin.     They   may  be  obtained  from   red    blood  corpuscles, 


108  .  PHYSIOLOGY 

where  they  form  the  giobiii  part  of  the  hsenioglobin  molecule,  or  from 
the  leucocytes  of  the  thymus  gland,  or  from  the  spermatozoa  of  fishes. 
The  histones  are  precipitated  from  their  watery  solutions  by  addition 
of  ammonia,  but  are  soluble  in  excess  of  this  reagent.  In  the  presence 
of  salts  they  are  coagulated  on  boiling.  With  cold  nitric  acid  they  give 
a  precipitate  which  dissolves  on  warming,  but  is  thrown  down  again  on 
cooling.  The  most  characteristic  feature  of  this  class  of  bodies  is, 
however,  the  high  proportion  of  diamine- acids  and  bases  contained  in 
their  molecule. 

(3)  ALBUMINS.  These  are  soluble  in  pure  water  and  are  pre- 
cipitated by  complete  saturation  with  ammonium  sulphate,  zinc 
sulphate,  or  sodio-magnesium  sulphate. 

Egg  Albumin  forms  the  greater  part  of  the  white  of  egg.  It 
gives  the  ordinary  protein  tests,  coagulates  on  heating  at  about 
75°  C,  and  is  precipitated  from  its  solutions  if  shaken  with  a  drop  of 
dilute  acetic  acid  in  excess  of  ether.  It  is  laevo-rotatory,  its  specific 
rotatory  power  being  —  35-5°. 

Serum  Albumin  occurs  in  large  quantities  in  the  blood  plasma, 
serum,  lymph,  and  tissue  fluids  of  the  body.  It  coagulates  at  75°  C, 
and  is  distinguished  from  egg  albumin  by  its  greater  specific  rotatory 
power,  —  56°,  and  by  the  fact  that  it  is  not  precipitated  by  ether  and 
sulphuric  acid.  Some  vegetable  proteins  belong  to  this  class,  e.g.  the 
le^icosin  of  wheat. 

(4)  GLOBULINS.  These  bodies  are  insoluble  in  pure  water  and 
require  the  presence  of  a  certain  amount  of  neutral  salt  to  dissolve 
them.  They  are  precipitated  from  their  solutions  by  complete  satura- 
tion with  magnesium  sulphate  or  by  half-saturation  with  ammonium 
sulphate.     The  chief  members  of  this  class  are  : 

Crystallin,  obtained  from  the  crystalline  lens  by  passing  a 
stream  of  carbon  dioxide  througli  an  aqueous  extract  of  this  body. 

Serum  Globulin  or  Paraglobulin,  a  constituent  of  blood  plasma 
and  blood  serum. 

Fibrinogen,  which  occurs  in  blood  plasma  and  is  converted  into 
fibrin  when  the  blood  clots. 

Paramyosinogen,  a  normal  constituent  of  muscle. 

Midway  between  these  two  groups  may  be  placed  the  nniscle 
protein,  myosin  (or  myosinogen),  which,  though  soluble  in  pure  water, 
resembles  the  class  of  globulins  in  the  ease  with  which  it  is  precipitated 
by  the  addition  of  neutral  salts. 

In  addition  to  the  members  of  the  globulins  named  above  and 
derived  from  the  animal  body,  proteins  allied  to  this  class  form  an 
important  constituent  of  plants,  and  are  found  in  large  quantities  in 
many  seeds  used  as  articles  of  food.  These  are  vegetable  globulins. 
Prominent  members  of  the  group  are  the  edestins,  which  may  be 


THE  PROTEINS  109 

obtained  from  hemp  seeds,  cotton  seeds,  and  sunflower  seeds,  zein 
from  maize,  letjitmin  from  beans. 

(y)  GLIADINS,  contained  in  cereals,  and  soluble  in  alcohol. 

(())  GLUTELINS,  proteins  also  obtained  from  cereals  and  soluble 
in  weak  alkalies. 

(7)  DERIVATIVES  OF  PROTEINS.  A.  METAPROTEINS.  These 
may  be  regarded  as  compounds  of  the  protein  molecule  or  of  part  of 
the  molecule  with  acid  or  basic  radicals. 

Acid  Albumin  is  formed  by  the  action  of  warm  dilute  acids  or  of 
strong  acids  in  the  cold  on  any  of  the  preceding  bodies.  If  a  weak 
alkali  be  added  so  as  to  nearly  neutralise  the  solution  of  acid  albumen, 
this  latter  is  precipitated.  If  the  precipitate  be  suspended  in  water 
and  heated,  it  is  coagulated  and  becomes  insoluble  in  dilute  acids  or 
alkalies. 

Alkali  Albumin  is  formed  by  the  action  of  strong  caustic  potash 
on  white  of  egg  or  on  any  other  protein,  or  by  adding  alkali  in  excess 
to  a  solution  of  acid  albumen.  It  is  precipitated  on  neutralisation  of 
its  solution. 

In  close  association  with  this  group  may  be  included  the  proteins  as  they 
occur  in  combination  Avith  the  metallic  salts,  such  as  copper  sulphate.  On 
splitting  off  the  copper  moiety  from  these  compounds,  the  protein  left  is 
practically  free  from  ash,  and  behaves  in  many  respects  like  an  albuminate, 
being  insoluble  in  absolutely  pure  water,  but  easily  dissolved  by  the  addition  of 
a  trace  of  free  acid  or  alkaU. 

A  group  of  protein  derivatives  described  by  Hopkins  is  produced  by  the 
action  of  the  free  halogens  on  protein  solutions.  We  get  in  this  waj'  two 
definite  classes  of  compounds.  One  class,  which  contains  the  largest  percentage 
of  halogen,  is  obtained  by  treating  a  protein  solution  with  chlorine,  bromine, 
or  iodine,  dissoh-ing  up  the  resultant  precipitate  in  alcohol  and  pouring  the 
alcoholic  solution  into  ether,  when  the  halogen  compound  is  throA\Ti  doA^Ti  as 
a  fine  white  precipitate.  By  dissoh-ing  this  precipitate  in  weak  soda  and 
precipitating  with  acid,  we  obtain  a  series  of  compounds  containing  only  about 
one-third  as  nuich  of  the  halogen  as  is  contained  in  the  first  precipitate, 
suggesting  tliat  the  halogen  forms  both  substitution  and  additive  compounds 
with  the  protein  molecule. 

Albumins,  globulins,  and  metaproteins  are  often  associated 
together  as  the  coagulable  proteins,  since  they  may  be  thrown  down 
entirely  from  their  solution  on  boiling  in  shghtly  acid  medium  in  the 
presence  of  neutral  salts. 

B.  HYDRATED  PROTEINS.  When  proteins  are  subjected  to 
the  action  of  superheated  water  or  steam,  or  heated  with  acids,  or 
acted  on  at  the  body  temperature  by  certain  ferments,  e.g.  pepsin, 
trypsin,  or  papain,  they  undergo  a  change  which  is  attended  by  the 
addition  of  a  number  of  molecules  of  water  to  the  protein  molecule 
(hydrolysis).  This  action,  when  carried  to  its  end,  results  in  tlu» 
production  of  the  amino-acids  which  we  have  already  dealt  with. 


110  PHYSIOLOGY 

These  hydrolytic  changes  proceed,  however,  by  a  series  of  stages, 
so  that  the  intermediate  products  still  present  many  of  the  protein 
reactions.     The  hydrated  proteins  are  divided  into  two  groups,  pro- 
teoses and  peptones.     The  formation  of  these  intermediate  products 
is   especially   marked   with   the    proteolytic   ferments.     Pepsin   with 
hydrochloric  acid,  the  ferment  of  the  gastric  juice,  for  example,  only 
breaks  down  the  protein  molecule  as  far  as  the  proteoses  and  peptones. 
Trypsin  also  gives  rise  to  both  proteoses  and  peptones  as  intermediate 
products.     The  action  of  these  ferments  on  proteins  is  in  fact  closely 
analogous  to  the  action  of  diastase  on  the  great  polysaccharide  molecule 
of  starch.     In  this  case,  as  intermediate  products  we  have  first  dextrins 
of  various  complexity,  secondly  maltose,  and  finally,  if  the  ferment 
maltase  be  also  present,  dextrose.     The  monotony  of  the  starch  mole.- 
cule  determines  a  great  similarity  of  composition  between  its  various 
disintegration  products.     It  may  be  regarded  as  an  anhydride  of  many 
(100  or  more)  molecules  of  a  hexose,  and  the  intermediate  stages  in  this 
hydrolysis  are  also  hexoses  and  their  anhydrides.     The  protein  molecule 
is  distinguished  by  the  variety  of  the  groups  which  enter  into  its  forma- 
tion, and  this  heterogeneous  character  of  the  molecule  renders  possible 
a  much  greater  variety  of  intermediate  products  than  we  find  in  the 
starches.     Thus  a  protein  molecule  may  consist  of  the  groups  A,  B, 
C,  D,  E,  F,  G,  H,  &c.     When  hydrolysis  occurs  it  may  result  in  the 
immediate  splitting  of!,  say,  of  part  of  group  A,  while  the  residue 
breaks  up  into  a  series  of  proteoses  whose  composition  may  be  repre- 
sented as  ABF,  ABC,  DFG,  BDEF,  &c.      With  further  hydrolysis 
these  groups  are  broken  into  still  smaller  ones,  and  the  penultimate 
stages  of  the  hydrolysis  will  be  polypeptides  similar  to  those  which 
have  been    synthetised  by  Fischer  from  the  ultimate  products  of 
protein  hydrolysis.     No  sharp  dividing  line  can  be  drawn  between  the 
proteoses,  peptones,  and  polypeptides.     Of  the  last  group  we  have 
already  seen  that  the  higher  members  give  the  biuret  reaction  as 
well  as  the  other  protein  reactions,  if  the  necessary  gToups,  e.g.  t}Tosine, 
tryptophane,  are  present  in  the  molecule.     The  proteoses  and  pep- 
tones are,  however,  ill-defined  bodies.     We  have  at  present  no  satis- 
factory means  of  isolating  the  different  members  of  these  gToups  and 
obtaining  them  in  a  state  of  chemical  puiity.     Their  classification  is 
therefore,  like   that   of   the  proteins  generally,  a  conventional  one, 
depending  on  their  solubilities  and  their  precipitability  by  neutral  salts, 
especially  ammonium  sulphate.     Both  proteoses  and  peptones  give  the 
xanthoproteic  and  Millon's  reactions  common  to  all  proteins,  and,  Like 
these,  are  precipitated  by  such  reagents  as  mercuric  chloride,  potassio- 
mercuric    iodide,    or    phosphotungstic    acid.     On    adding    excess    of 
caustic  potash  and  a  drop  of  dilute  copper  sulphate  to  solutions  of 
either  of  these  classes  of  bodies,  a  pink  colour  is  produced  which 


THE  PR0TEIN8  ]  1 1 

deepens  to  a  violet  on  addition  of  more  copper  (the  biuret  reaction). 
Their  solutions  can  be  boiled  without  undergoing  coaLrulation.  Many 
of  them  may  be  thrown  down  from  their  solutions  by  absolute  alcohol, 
but  are  not  rendered  insoluble  even  by  prolonged  standing  under  the 
alcohol.  The  characters  of  the  different  members  of  these  groups 
will  be  considered  at  greater  length  when  deaUng  with  the  changes 
undergone  by  the  proteins  during  the  process  of  digestion.  At 
present  we  may  merely  summarise  the  distinguishing  features  of  these 
two  classes. 

(«)  Proteoses,  e.q.  albumose  from  albumin,  caseose  from  casein, 
elastose  from  elastin.  All  of  these  are  precipitated  from  their  solu- 
tions on  saturation  with  ammonium  sulphate.  In  the  presence  of  a 
neutral  salt  they  give  a  precipitate  on  the  addition  of  nitric  acid. 
This  precipitate  is  dissolved  on  heating  the  solution,  but  reappears  on 
cooling.  All,  with  the  exception  of  heteroalbumose,  are  soluble  in 
pure  water,  and  all  are  soluble  in  w^eak  salt  solutions  or  dilute  acids 
or  alkalies.     They  are  slightly  diffusible  through  animal  membranes. 

(6)  Peptones,  e.ij.  fibrin  peptone,  gluten  peptone.  These  are  all 
soluble  in  pure  water,  diffuse  fairly  readily  through  animal  mem- 
branes, but  otherwise  give  the  same  reactions  as  albumoses.  From 
the  latter  class  peptones  are  distinguished  by  the  fact  that  they  are  not 
precipitated  on  saturation  of  their  solutions  either  in  acid  or  alkaline 
reaction  with  ammonium  sulphate  or  any  other  neutral  salt.  Many  of 
them  are  soluble  in  alcohol. 

(8)  THE  PHOSPHOPROTEINS.  In  this  class  may  be  grouped  a 
number  of  substances  of  very  diverse  properties  which,  however, 
resemble  one  another  in  containing  phosphorus  as  an  integral  part 
of  their  molecule.  When  subjected  to  digestion  with  pepsin  and 
hydrochloric  acid  they  are  dissolved,  but  a  small  quantity  of  a  phos- 
phorus-containing complex  may  remain  behind  undissolved.  This 
residue  has  been  called  paranuclein  or  pseudonuclein.  It  is  in  reality 
derived  from  nucleoprotein,  w^hich  is  present  in  the  phosphoprotein 
as  impurity  and  should  be  called  simply  nuclein.  The  phosphoproteins 
have  markedly  acid  characters.  They  are  insoluble  in  pure  water, 
easily  soluble  in  alkalies  and  ammonia  from  wliich  the  original  body 
is  thrown  down  again  on  addition  of  acid.  Their  solutions  in  alkali 
are  not  coagulated  by  heating.  To  this  class  belong  caseinogen,  the 
chief  protein  of  milk,  vitellin,  the  main  protein  in  the  yolk  of  egg,  and 
the  vitellins  in  the  eggs  of  fishes  and  frogs.  The  vitellins  are  generally 
associated  with  a  large  amount  of  lecithiji.  The  phosphoproteins  differ 
from  the  nucleoproteins,  which  also  contain  phosphorus,  in  the  facts 
that  they  are  readily  decomposed  by  caustic  alkali  with  the  libera- 
tion of  phosphoric  acid,  and  do  not  contain  purine  bases.  The  phos- 
phorus of   the  nucleoproteins  is  not  split  off  by  allcali  (1  per  cent.), 


112  PHYSIOLOGY 

and  on  hydrolysis  the  nucleic  acid  constituent  gives  rise  to  purine 
bases. 

(9)  CONJUGATED  PROTEINS.  Various  complex  bodies  which  play 
an  important  part  in  building  up  cells  and  in  the  various  processes 
of  the  body  make  up  this  group  of  compounds.  They  resemble  one 
another  only  in  the  fact  that  in  each  of  them  a  protein  radical  is  com- 
bined with  some  other  body,  often  spoken  of  as  the  prosthetic  group.* 

(a)  Chromoproteins.  Of  this  class,  consisting  of  a  colouring 
matter  combined  with  a  protein,  the  most  important  is  hcBmoglobin. 
This  substance,  which  is  the  red  colouring- matter  of  the  red  corpuscles 
of  the  blood  and  plays  an  important  part  in  the  processes  of  respiration, 
acting  as  an  oxygen  carrier  from  the  lungs  to  the  tissues,  is  com- 
posed of  the  protein,  giobin,  united  with  an  iron-containing  body, 
hsematin.  Oxyhsemoglobin  contains  from  4-5  per  cent,  hsematin 
(C32H32N404Fe).  It  is  easily  crystallisable,  and  its  physical  and 
chemical  characters  have  therefore  been  more  precisely  determined 
than  is  the  case  with  most  other  members  of  the  group  of  conjugated 
proteins.  We  shall  have  to  deal  more  fully  with  its  properties  in  the 
chapters  on  Blood  and  Eespiration. 

(6)  The  Nucleoproteins.  These  are  formed  by  the  combina- 
tion of  a  phosphorised  organic  acid,  nucleic  acid,  with  a  protein 
which  may  belong  to  any  of  the  classes  we  have  enumerated  above. 
Some  of  the  best-marked  members  of  this  group  consist  of  compounds 
of  nucleic  acid  "with  basic  histones  or  protamines.  The  combination 
between  protein  and  the  prosthetic  group  seems  to  take  place  in  two 
stages.  If  a  nucleoprotein  be  subjected  to  gastric  digestion  a  large 
amount  of  the  protein  goes  into  solution  as  proteose  or  peptone, 
leaving  an  insoluble  remainder.  This  precipitate  is  not,  however, 
nucleic  acid,  but  still  contains  a  protein  gTOup,  the  compound  being 
spoken  of  as  nuclein.  From  the  latter  nucleic  acid  can  be  split  off  by 
heating  with  strong  acids  or  other  means.  The  nucleoproteins  are 
soluble  in  water  and  salt  solutions,  and  are  easily  soluble  in  dilute 
alkalies.  They  have  acid  characters  and  are  precipitated  by  the 
addition  of  acids.  The  nucleins,  on  the  other  hand,  are  insoluble  in 
water  and  salt  solutions,  but  are  easily  dissolved  by  dilute  alkalies. 
The  nucleins  and  nucleoproteins  form  the  chief  and  invariable 
constituent  of  cell  nuclei.  They  may  be  therefore  prepared  from  the 
most  diverse  organs.  The  heads  of  the  spermatozoa  of  the  salmon 
consist    entirely    of    nuclein.      Miescher    aiid    Schmiedeberg   found 

*  By  the  Germans  the  term  '  proteid  '  is  often  applied  to  this  group.  In 
English,  however,  the  term  '  proteid  '  has  been  generally  used  for  the  simple 
protein  kno^vn  to  the  Germans  as  '  Eiweisskorper.'  On  account  of  the  con- 
fusion which  has  arisen  from  this  double  use  of  the  term  '  proteid,'  I  have 
attempted  to  avoid  it  altogether  in  this  volume. 


THE  PK0TEIN8  Jl.j 

that  the  nuclein  obtained  from  this  source  contained  GO-5  per  cent, 
nucleic  acid  and  35-56  protamine,  and  was  in  fact  a  nucleate  of  prota- 
mine. The  nuclein  derived  from  the  spermatozoa  of  echinoderms 
has  been  found  to  be  a  compound  of  nucleic  acid  and  histone.  From 
.organs  rich  in  cells,  such  as  the  thymus  and  the  pancreas,  and  from 
nucleated  red  blood  corpuscles,  nucleoproteins  may  be  obtained 
which  can  be  broken  down  into  nuclein  and  protein,  the  nuclein  again 
being  composed  of  a  protein  residue  with  nucleic  acid. 

As  first  extracted  from  the  animal  cell  the  nucleoproteins  are  associated 
with  a  considerable  proportion  of  lecithin,  and  in  this  labile  compound  form  the 
'  tissue  fibrinogen  '  of  Wooldridge.  To  prepare  this  substance  an  organ  rich 
in  cells,  such  as  the  thymus,  is  minced  and  extracted  with  water  or  normal 
salt  solution.  After  separating  the  cells  by  means  of  the  centrifuge,  the  clear 
fluid  is  decanted  off  and  acidified  with  acetic  acid.  A  precipitate  is  produced 
consisting  of  'tissue  fibrinogen,'  This  substance  is  soluble  in  excess  of  acid 
and  is  easily  soluble  in  alkalies.  All  the  tissue  fibrinogens  are  highly  unstable 
bodies  and  undergo  changes  in  the  mere  act  of  precipitation  and  re-solution. 
When  injected  into  the  blood  they  cause  intravascular  clotting.  On  digestion 
with  gastric  juice  they  jield  a  precipitate  of  nuclein,  and  tliis  precipitate  contains 
a  large  proportion  of  the  lecithin  present  in  the  original  substance.  In  the 
nucleoproteins  nucleic  acid  is  combined  with  proteins  in  two  degrees,  a  large 
portion  of  the  protein  being  separable  by  gastric  digestion,  while  the  remainder 
needs  stronger  reagents  for  its  dissociation.  The  relation  of  the  two  portions 
of  the  nucleoprotein  may  be  represented  therefore  by  the  follomng. schema  : 

Nucleo-protein 
Protein  Nuclein 


Protein  Nucleic  acid 

(generally  histone 
or  protamine) 

Since  we  have  already  dealt  with  the  chemical  constitution  of 
the  proteins,  it  remains  only  to  discuss  the  nature  of  imcleic  acid. 
By  various  means,  all  of  which  involve  hydrolysis,  the  nucleic  acid 
may  be  broken  up  into  its  proximate  constituents.  These  differ 
according  to  the  source  of  the  nucleic  acid.  Whatever  the  source,  the 
disintegration  products  belong  to  closely  allied  groups  of  substances. 
These  may  be  gi'ouped  as  follows  . 

(1)  Phosphoric  Acid.  The  proportion  of  phosphorus  varies 
within  but  narrow  limits  in  the  different  nucleic  acids,  the  average 
being  about  10  per  cent.  It  is  probable  that  the  phosj)horic  acid 
represents,  so  to  speak,  the  combining  medium  for  the  groups  contained 
in  the  nucleic  acid  molecule,  as  is  the  case  A\ith  the  various  groups 
which  make  up  the  lecithin  molecule. 

(2)  The  Pvrine  Bases.  Among  the  products  of  disintegration 
of  nucleic  acid  we  find  constantly  one  of  the  bases  adenine,  C5Hj,N5.  and 

8 


114  PHYSIOLOGY 

guanine  (CgHsNgO).  These  substances,  with  the  products  of  their 
oxidation,  xanthine,  C5H4N4O.2,  hypoxanthine,  C5H4N4O.,  have  long 
been  known  to  be  closely  allied  to  uric  acid,  O5H4N4O3,  but  their  true 
relationships  have  only  been  thoroughly  known  since  the  researches  of 
Fischer  on  this  group.  According  to  Fischer  they  can  be  all  regarded 
as  derivatives  of  the  body  purine, 

^N  -«CH 

I  I 

"HC    ^C—NH' 

II  II  >M« 

Each  group  in  this  purine  ring  is  generally  designated  with  a  number 
indicated  in  the  structural  formula,  in  order  that  it  may  be  possible 
to  represent  the  position  of  any  substituted  groups  in  its  derivatives. 
Uric  acid  itself  is  2-6-8-trioxypurine  with  the  following  formula  : 

HN— CO 

I  I 

OC      C— NH 

I        II         >o 
HN—  C— NH^ 

It  can  be  synthetised  by  fusing  together  in  a  sealed  tube  trichloro- 
lactamide  and  urea.     Thus  : 

NH2     CONH2  NH— CO 

II  II. 

CO   +  CHOH  +  NHax  =    CO      C— NH  +  NH4CI.  +  2HC1 

II  /CO  I         II  /CO 

NH,     CCI3  NHa^  NH— C^NH/ 

The  relation  of  xanthine,  hypoxanthine,  guanine,  and  adenine  to  uric 
acid  is  shown  by  the  following  formute  : 


NH— CO 

1           1 

HN- 

-CO 

1           1 
CO      C— NH\ 

1       II          >co 

CO- 

1 

-O-NH, 

11            >CH 

NH— C— NH^        . 

HN- 

Uric  acid 

Xanthine 

2-6-8-trioxypurine 

2-6-dio 

xypurine 

HN— CO 

1          1 

N    =  C.NH2 

1           1 

NH— CO 

1           1 

1          1 
HC     C  - 

-NH 

1           1 
HC       (>-NHx 

I  1 
NH2C        C— NHx 

II  II           >CH 
N—   C— N   -^ 

II        II 
N  — C  - 

.CH 

-N  ^ 

II         II           ^CH 
N—    '(^-N     ^ 

Hypoxanthine 

Adenine 

Guanine 

6-oxypurine 

G -amino -purine 

2-amino  6-oxypurine 

Closely  allied  to  this  group  of  bodies  are  the  chief  constituents  of  tea, 


THE  PROTEINS  115 

coffee,  and  cocoa,  namely  caffeine,  which  is  trimethyl  dioxypurine,  and 
theobromine,  which  is  dimethyl  dioxypurine.  From  the  structural 
formulae  given  it  will  be  seen  that  the  purine  radical  contains  two 
nuclei.     The  nucleus 

N— C 

C     0 

N— C 
is  spoken  of  as  tlie  pyrimidine  nucleus,  pyrimidine  having  the  formula 

^V— «CH 

II        II 

The  other  is  the  radical  which  we  have  met  wth  already  in  histidine, 
a  disintegration  product  of  proteins,  namely   iminazol  : 

HC— NH 


^  CH 


HC— N 


^ 


Besides  the  purine  bases  proper,  we  meet  among  the  disintegration 
products  of  nucleic  acid  with  a  series  of  bases  derived  from  the  pyrimi- 
dine ring.     These  are  uracil,  thymine,  and  cytosine. 
Uracil  is  2-6-dioxypyrimidine, 

NH— CO 
CO      CH 

NH— CH 

Thymine  is  5-methyl  uracil, 

NH— CO 

I  I 

CO     C.CH, 

I  II 

NH— CH 

while  CYTOSINE  is  G-amino-2-oxypyrimidine, 

NH— C.NH2 

CO     CH      . 

I         II 
N    =CH 


116  PHYSIOLOGY 

Besides  these  two  groups  of  nitrogenous  compounds  derived  from 

the  purine  and  pyrimidine  rings,  many  nucleic  acids  yield  on  hydrolysis 

a  carbohydrate.     Thus,  Hammarsten  has  isolated  a  pentose,  xylose, 

from  the  nucleoproteins  of  the  pancreas.      It  is  supposed  that  the 

nucleic  acid  of  the  thymus  gland  contains  a  hexose,  since  it  is  possible 

to  split  ofi  from  it  IsevuUnic  acid,  which  is  one  of  the  first  products  of 

the  decomposition  of  a  hexose.     The  complex  constitution  of  the 

nucleic  acids  and  nucleoproteins   may  be  rendered  clearer  from  the 

following  schema  : 

Nucleo -protein 
on  digestion  yields  ^ — ^^^^ 

nuclein         proteoses  and  peptones 
dissolved  in  alkali   and   precipitated 
with  hydrochloric  acid  yields 

nucleic  acid  acid  derivatives  of  protein,  histones 

or  protamines 
hydrolysed  yields 


phosphoric  acid  reducing  sugar  purine  bases  pyrimidine  bases 

pentose  or  adenine  uracil 

hexose  guanine  thymine 

cytosine 

Tt  must  not  be  imagined,  however,  that  all  these  disintegxation  pro- 
ducts are  present  in  all  nucleic  acids.  Thus  the  nucleic  acid  derived 
from  the  pancreas,  the  so-called  guanylic  acid,  yields  of  the  purine 
bases  only  guanine,  and  of  the  pyrimidine  bases  only  thymine  and  uracil, 
and  every  variety  is  met  "«dth  as  we  analyse  the  nucleic  acids  of  different 
origin.  The  fact  that  nucleic  acid  is  a  characteristic  and  necessary 
constituent  of  all  nuclei  adds  interest  to  the  divergence  of  its  con- 
stituent radicals  from  those  which  distinguish  the  proteins  of  the  cell 
protoplasm.  Further  importance  is  lent  to  this  section  of  the  chemistry 
of  the  body  by  the  close  relationship  which  we  shall  have  to  study  later 
between  the  nuclein  metabolism  of  the  body  and  the  production  and 
excretion  of  uric  acid. 

(c)  The  Glycoproteins.  In  the  glycoproteins  the  prosthetic 
group  is  represented  by  a  carbohydrate  radical,  generally  containing 
nitrogen,  such  as  glucosamine  or  galactosamine.  They  are  spht  into 
their  two  constituents,  protein  and  carbohydrate  radical,  on  prolonged 
boihng  with  dilute  mineral  acids  or  by  the  action  of  alkahes.  They 
may  be  divided  into  the  two  main  groups  of  mucins  and  mucoids. 

The  mucins  play  a  large  part  in  the  animal  kingdom  as  protective 
agents.  They  form  the  slimy  secretion  which  covers  the  inner  surface 
of  the  mucous  membranes  and  the  outer  surface  of  many  marine 


THE  PROTEINS  117 

animals,  and  is  secreted  either  by  the  goblet  cells  of  the  epithelium  or 
by  special  groups  of  cells  collected  together  to  form  a  mucous  gland. 
They  may  be  precipitated  from  their  solutions  or  semi-solutions  by 
the  addition  of  acids,  and  after  precipitation  need  the  addition  of 
alkalies  for  their  re-solution.  They  are  not  coagulable  by  heat.  The 
presence  of  their  protein  moiety  causes  them  to  give  the  various 
typical  protein  tests,  such  as  the  xanthoproteic,  Millon's,  the  biuret 
reaction,  and  so  on.  Prolonged  boiling  with  acids  splits  the  molecule, 
with  the  production  of  acid  albumin  and  albumoses  and  glucosamine. 
From  the  mucin  of  frogs'  eggs  a  similar  treatment  results  in  the  produc- 
tion of  galactosamine. 

With  the  mucins  may  be  classified  certain  bodies  which  have  been  derived 
from  ovarial  cysts,  namely,  pseudomucin  and  paramucin.  Pseudomucin  occurs 
as  a  constituent  of  the  colloid  material  from  ovarian  tumours.  It  forms  slimy 
solutions  which  do  not  coagulate  by  heat  and  are  not  precipitated  by  acetic 
acid.  It  is  precipitated  by  alcohol,  the  precipitate  being  soluble  in  water  even 
after  standing  a  long  time  under  the  alcohol.  On  boUing  with  acid  it  gives 
a  reducing  substance.  Paramucin  differs  from  the  above  in  reducing  Fehling's 
solution  before  boiling  with  acids.  Otherwise  it  resembles  pseudomtcin. 
Leathes,  in  investigating  this  body,  isolated  from  it  a  reducing  substance  which 
apparently  was  an  amino-derivative  of  a  disaccharide,  perhaps  in  combination 
with  glycuronic  acid. 

The  mucoids  include  a  number  of  substances  which  may  be 
extracted  from  various  tissues  by  the  action  of  weak  alkalies,  e.g,  from 
tendons,  bone,  and  cartilage.  The  best  studied  example  of  this  group 
is  the  chondromucoid  which,  with  collagen,  forms  the  ground  substance 
of  cartilage.  Chondromucoid  is  especially  rich  in  sulphur  and  gives 
protein  by  long  treatment  with  weak  alkali.  On  boiling  for  a  short 
time  with  acid  it  is  decomposed  into  sulphuric  acid  and  chondroitin, 
and  this  latter,  on  further  action  of  the  acid.,  is  converted  into  a  sub- 
stance chondrosin,  which  is  certainly  an  amino-derivative  of  a  poly- 
saccharide containing  the  elements  of  glycirronic  acid  and  an  amino- 
disaccharide.  Chondroitin-sulphuric  acid  occurs  not  only  in  cartilage 
but  also  in  bone,  yellow  elastic  tissue,  white  fibrous  tissue,  and  as  a 
constant  constituent  of  the  lardacein  or  amyloid  substance  which 
occurs  as  a  deposit  in  the  middle  coat  of  the  blood-vessels  as  the 
result  of  syphilis  or  long-continued  suppuration,  and  gives  rise  to  the 
condition  known  as  '  lardaceous  disease.'  Another  example  of  this 
class  of  mucoids  is  ovomucoid,  which  is  a  constituent  of  egg-white. 
In  order  to  prepare  ovomucoid  the  globulin  and  albumin  are  pre- 
cipitated by  boiling  diluted  egg-white.  From  the  filtrate  ovomucoid 
can  then  be  thrown  down  by  alcohol.  A  similar  body  has  been 
prepared  from  blood  serum.  Both  these  nmcoids  yield  a  large  amount 
of  reducing  substance  on  hydrolysis.  Thus  from  1(30  grm.  of  ovo- 
mucoid it  is  possible  to  prepare  30  grm.  of  glucosamine. 


118  PHYSIOLOGY 

(10)  THE  ALBUMINOIDS  OR  SCLERO-PROTEINS.  Under  this 
Leading  are  grouped  a  number  of  diverse  substances  which  play  an 
important  part  in  building  up  the  framework  of  the  body.  Their 
value  as  skeletal  tissues  eeems  to  be  determined  by  their  insoluble 
character.  On  this  account  it  is  practically  impossible  to  speak  of 
piu-ifying  them.  Jn  every  case  we  can  simply  take  the  residue  of  a 
skeletal  tissue  which  is  left  after  extraction  of  the  soluble  constituents. 
When  broken  down  by  the  action  of  strong  acids  they  yield  a  series 
of  disintegration  products  which  are  included  among  those  we  have 
already  studied  as  the  disintegration  products  of  proteins.  Their 
difference  from  the  proteins  which  are  employed  in  metabolism  for 
their  nutritive  value  is  caused  either  by  the  absence  of  certain  groups 
common  to  all  the  nutritive  proteins,  by  the  presence  of  an  excess  of  one 
or  two  groups,  or  by  the  presence  of  certain  polypeptides  which 
present  considerable  resistance  to  the  action  of  digestive  ferments. 
This  class  plays  the  part  in  the  animal  economy  which  in  the  vegetable 
kingdom  is  filled  by  the  anhydrides  of  the  hexoses  and  pentoses,  e.g. 
the  celluloses,  lignin,  the  pentosanes,  &c.  Collagen  forms  the  main  con- 
stituent of  white  fibrous  tissue  and  the  ground  substance  of  bone  and 
cartilage.  It  is  insoluble  in  water,  hot  or  cold,  and  in  trypsin.  Under 
the  action  of  acids  or  when  subjected  to  prolonged  boiling  with  water, 
especially  under  pressure,  it  is  converted  into  gelatin,  which  is  soluble 
in  hot  water,  forming  a  colloidal  solution  liquid  at  high  temperatures, 
but  setting  to  a  jelly  when  cold.  When  subjected  to  acid  hydrolysis  it 
gives  a  series  of  amino-acids  from  which  tyrosine  and  tryptophane  are 
wanting.  On  this  account  gelatin  does  not  give  any  reaction  either 
with  Millon's  reagent  or  with  glyoxyhc  acid.  On  the  other  hand,  there 
is  a  preponderance  of  such  groups  as  glycine  and  phenylalanine,  and 
it  is  probable  that  glycine,  phenylalanine,  and  leucine  are  joined 
together,  perhaps  with  other  amino-acids,  to  form  a  polypeptide 
which  is  not  attacked  by  digestive  ferments,  and  therefore  determines 
the  resistance  of  the  original  collagen  molecule  to  solution.  Gelatin 
is  precipitated  by  tannic  acid,  but  not  by  acetic  acid.  It  is 
dissolved  with  hydrolysis  by  gastric  juice  or  by  pancreatic  juice, 
whereas  collagen,  its  anhydride,  is  unaffected  by  the  latter.  On 
prolonged  boiUng  in  water  it  is  converted  into  a  modification  which 
does  not  form  a  jelly  on  cooling.  Under  the  action  of  formaldehyde 
it  is  converted  into  an  insoluble  modification  which  does  not  melt  on 
warming. 

Reticulin.  This  name  has  been  applied  to  the  tissue  which  forms  the  support- 
ing network  of  adenoid  tissue,  and  has  also  been  described  in  the  spleen,  the 
mucous  membrane  of  the  intestine,  liver,  and  kidneys.  It  differs  from  collagen 
in  resisting  digestion  by  gastric  juice,  and  also  in  containing  ])h()spliorus  in  organic 
combination.  According  to  Halliburton  there  is  no  essential  difTerence  between 
reticulin  and  collagen. 


THE  PROTEINS 


119 


The  Jceratins  are  produced  by  the  modification  of  epithelial  cells  and 
form  the  horny  layer  of  the  skin  as  well  as  the  main  substance  of  hairs, 
wool,  nails,  hoofs,  horns,  and  feathers.  They  are  distinguished  by  their 
insolubility  in  water,  dilute  acids  or  alkalies,  and  in  the  higher  animals 
pass  through  the  ahmentary  canal  unchanged.  Although  differing  in 
their  elementary  composition,  according  to  the  tissue  from  which  they 
are  prepared,  they  are  all  distinguished  by  the  very  large  amount  of 
sulphur  present  in  their  molecule.  The  greater  part  of  this  sulphur  is 
in  the  form  of  cystine,  of  which  as  much  as  10  per  cent,  can  be  ex- 
tracted from  keratin.  They  also  yield,  on  acid  hydrolysis,  tyrosine  in 
larger  quantities  than  is  the  case  with  the  ordinary  proteins. 

Neurolceratin,  which  forms  the  basis  of  the  neuroghal  frame- 
work of  the  central  nervous  system,  must  be  grouped  by  its  general 
behaviour  as  well  as  by  its  origin  with  the  keratins.  It  resembles  the 
other  members  of  this  class  in  its  insolubility  and  in  its  high  content  in 
sulphur.  It  is  extracted  from  nervous  tissues  by  boiling  these  \dth. 
alcohol  and  ether  and  then  submitting  the  tissue  to  prolonged  tryptic 
digestion,  which  leaves  the  neurokeratin  unaffected. 


Fibroin 

£eratin 

Keratin 

Keratin 

of 

Elastin 

from 

from 

from 

Gelatin 

silk 

horn 

horsehair 

feathers 

Glycine  .... 

36-0 

25-75 

0-45 

4-7 

2-6 

16-5 

Alanine 

21-0 

6-6 

1-6 

1-5 

1-8 

0-8 

Amino-valerianic  acid 

0-0 

1-0 

4-5 

0-9 

0-5 

10 

Proline  .... 

l.r._-scm 

1-7 

5-2 

Leucine  .... 

1-5 

21-4 

15-3 

71 

8-0 

21 

Phenylalanine 

1-5 

3-9 

1-9 

0-0 

00 

0-4 

Glutamic  acid 

00 

0-8 

17-2 

3-7 

2-3 

0-88 

Aspartic  acid 

l-rescnt 

present 

2-5 

0-3 

11 

0-56 

Cystine  .... 

— 

— 

7-5 

— 

— 

Serine     . 

1-C 



11 

0-6 

0-4 

0-4 

Tyrosine 

10-5 

0-34 

3-6 

3-2 

3-6 

00 

Tryptophane 

— 

— 

— 

— 

— 

00 

Lysine    . 

trace-. 

— 

0-2 

11 

— 

2-75 

Arginine 

10 

0-3 

2-7 

4-5 

— 

7-62 

Histidine 

small 
amount 

— 

— 

00 

— 

0-4 

Oxyproliiu' 

" 

— 

30 

Elastin  is  a  constant  constituent  of  the  connective  tissues,  where 
it  forms  the  elastic  fibres.  In  some  localities,  as  in  the  ligamentum 
nuchse,  practically  the  whole  tissue  is  made  up  of  these  fibres.  Elastin 
is  insoluble  in  water,  alcohol,  or  ether,  or  in  dilute  acids  and  alkalies. 
It  is  slowly  dissolved  on  prolonged  treatment  with  gastric  juice,  but  is 
practically  unaffected  in  the  alimentary  canal.  It  gives  the  xantho- 
proteic and  Millon's  tests. 


120  PHYSIOLOGY 

Other  members  of  this  group  are  fibroin,  which  forms  the  main 
substance  of  silk,  spongin,  the  horny  framework  of  sponges,  conchiolin, 
the  ground  substance  of  shells,  and  perhaps  the  amyloid  substance  or 
iardaoein  which  we  have  already  mentioned  in  connection  with  the 
mucoids.  All  these  sclero- proteins  present  considerable  differences 
in  their  qualitative  and  quantitative  composition  in  amino-acids.  Their 
proximate  composition  is  shown  in  the  Table  on  the  preceding  page 
(Abderhalden). 

We  have  finally  to  mention  a  miscellaneous  collection  of  bodies 
which  are  allied  to  the  proteins  and  are  distinguished  by  their  extreme 
insolubility.  They  are  often  designated  as  albumoids.  Of  their  com- 
position we  know  practically  nothing.  Under  this  name  are  grouped 
such  substances  as  those  forming  the  membrana  propria  of  glands,  the 
sarcolemma  of  striated  muscle,  the  albumoid  of  the  crystalline  lens, 
the  ground  substance  of  the  chorda  dorsalis,  the  organic  basis  of  fish 
scales,  and  many  similar  substances.  In  every  case  the  substance  is 
characterised  necessarily  according  to  its  place  of  origin,  little  or 
nothing  being  known  as  to  its  chemical  composition. 


SECTION  VI 

THE  MECHANISM    OF    ORGANIC    SYNTHESIS 

THE    ASSIMILATION    OF    CARBON 

The  building  up  of  protoplasm  from  the  material  which  is  available 
at  the  earth's  surface  must  be  an  endothermic  process.  The  food 
presented  to  the  plant  contains  the  necessary  elements,  but  as  a 
rule  in  a  state  of  complete  oxidation.  The  energy  of  the  living 
plant,  as  of  animals,  is  derived  almost  entirely  from  the  oxidation  of 
its  constituents.  The  building  up  of  unorganised  into  organised 
material  must  therefore  be  effected  at  the  expense  of  energy  supplied 
from  without.  The  source  of  this  energy  is  the  sun's  rays.  The 
machine  for  the  conversion  of  solar  radiant  energy  into  the  chemical 
potential  energy  of  protoplasm  is  the  green  leaf.  Here  a  deoxidation  of 
the  carbon  dioxide  of  the  atmosphere  takes  place,  Tsdth  the  production  of 
carbohydrates,  generally  in  the  form  of  starch.  The  formation  of  starch 
must  be  regarded  as  the  first  act  in  the  life-cycle,  since  this  substance 
serves  as  a  soiu-ce  of  energy  to  the  aheady  formed  protoplasm  in  its 
work  of  building  up  all  the  other  constituents  of  the  hving  cell.  It  is 
the  solar  energy  captured  by  the  green  leaf  which  is  utilised  by  all 
plants  devoid  of  chlorophyll,  as  well  as  by  the  whole  animal  kingdom. 

There  are  one  or  tMO  exceptions  to  this  statement.  Thus  the  bacterium 
nitrosomonas,  described  by  Winogradsk3%  grows  on  a  medium  devoid  of  all 
organic  constituents,  and  derives  the  energy  for  its  constructional  acti\Tty 
from  that  set  free  in  the  conversion  of  ammonia  into  nitrites.  The  sulphm* 
bacteria  apparently  derive  their  energy  from  the  decomposition  of  hydrogni 
sulphide  and  tlic  liberation  of  sulphur. 

The  fundamental  importance  of  this  process  of  assimilation  for 
the  whole  of  physiology  justifies  some  account  of  the  researches  which 
have  been  directed  to  the  elucidation  of  its  mechanism.  The  produc- 
tion of  oxygen  by  the  green  plant  was  first  discussed  by  Priestley  in 
1772,  and  a  few  years  later  Ingenhaus  showed  that  this  production 
occurred  only  in  the  light  and  was  effected  only  by  green  plants.  De 
Saussure  (1804)  pointed  out  that  the  essential  process  concerned  was  a 
setting  free  of  the  oxygen  from  the  carbon  dioxide  of  the  atmosphere, 
and  recognised  that  the  co-operation  of  water  was  also  necessary. 
Mohl  in  1851  observed  the  formation  of  starch  grains  in  the  chloro- 

121 


122  PHYSIOLOGY 

phyll  corpuscles,  and  regarded  these  as  the  first  products  of  assimila- 
tion. The  organs  of  carbon  dioxide  assimilation  are  the  chloroplasts. 
These,  which  are  responsible  for  the  gxeen  coloiu?  of  plants,  are  generally 
small  oval  bodies  embedded  in  the  cytoplasm,  but  sometimes,  as  in 
spirogyra,  may  have  the  form  of  spiral  bands.  In  a  plant  which  has 
been  kept  for  some  time  in  the  dark,  or  in  an  atmosphere  free  from 
carbon  dioxide,  they  present  no  enclosed  granules.  Within  three  to 
five  minutes  after  exposure  to  light  in  the  presence  of  carbon  dioxide, 
starch  granules  make  their  appearance  within  them,  and  gxow  rapidly, 
assuming  the  typical  laminated  structiure.  Engelmann  has  pointed  out 
a  means  by  which  it  can  be  proved  that  the  chloroplasts  carry  out  this 
process  without  the  co-operation  of  the  rest  of  the  cytoplasm.  Certain 
bacteria  have  a  great  avidity  for  oxygen  and  present  movements  only 
in  the  presence  of  this  gas.  If  a  filament  of  spirogp-a  be  placed  in  a 
suspension  of  these  bacteria  and  be  examined  under  a  microscope,  the 
bacteria  will  be  seen  to  congregate  in  the  immediate  neighbourhood  of 
the  chlorophyll  bands.  The  same  phenomenon  is  observed  in  the  case 
of  chlorophyll  corpuscles  isolated  by  breaking  up  the  cells  in  which 
they  were  contained.  These  corpuscles  therefore  take  up  carbon 
dioxide  and  water,  and  form  carbohydrate  and  oxygen,  as  follows  : 

n{6C0,  +  5H2O)  =  (CeHioO^),,  +n(602) 

The  whole  structiue  of  the  green  leaf  is  directed  to  the  fm-thering  of 
this  process.  Its  cells  contain  chlorophyll  corpuscles,  which,  change 
their  position  according  to  the  intensity  of  the  illumination.  A  free 
supply  of  air  to  all  the  cells  is  provided  by  means  of  the  stomata 
on  the  under  surface  of  the  leaf.  Horace  Brown  has  shown  that  the 
ra'"e  at  which  carbon  dioxide  diffuses  through  such  fine  openings  is  as 
great  as  if  the  whole  leaf  were  an  absorbing  surface.  We  get,  therefore, 
optimum  absorption  of  carbon  dioxide  by  the  leaf,  with  the  maximum 
protection  of  the  absorbing  tissue  and  the  necessary  limitation  of  loss 
of  water  by  transpiration. 

In  view  of  the  very  small  amount  of  carbon  dioxide  in  the  atmo- 
sphere, the  extent  of  the  assimilatory  process  is  remarkable.  One 
square  metre  of  leaf  of  the  catalpa  can  lay  on  1  grm,  of  solid  per 
hour,  using  up  for  this  piupose  784  ccm,  carbon  dioxide.  The  rapidity 
of  assimilation  is  increased  within  limits  by  increasing  the  intensity 
of  the  light  falling  on  the  plant,  though  an  over-stimulation  of  the 
process  is  prevented  by  the  movements  of  the  chloroplasts  just  men- 
tioned. It  is  also  increased  by  raising  the  percentage  of  carbon  dioxide 
in  the  atmosphere  supplied  to  the  leaf.  The  optimum  percentage  of 
carbon  dioxide  will  of  course  vary  with  the  other  conditions  of  the  leaf. 
In  certain  experiments  Kreusler  found  the  optimum  to  be  about 
1  per  cent.     Taking  the  amount  of  assimilation  in  normal  air  witli 


THE  MECHANISM  OF  ORGANIC  SYNTHESIS     123 

•03  per  cent,  carbon  dioxide  at  100,  the  assimilation  in  an  atmosphere 
containing  1  per  cent,  was  237,  and  was  not  increased  by  raising  the 
percentage  of  carbon  dioxide  to  7  per  cent.  Owing  to  the  decomposi- 
tion of  the  organic  matter  of  the  .soil,  the  percentage  of  carbon  dioxide 
near  the  ground  is  always  greater  than  in  the  higher  strata  of  the 
atmosphere — a  fact  which  is  taken  advantage  of  by  the  low-growing 
plants  and  herbage.  Other  necessary  conditions  of  assimilation  are 
the  presence  of  water  and  the  maintenance  of  a  certain  external 
temperatm"e.  The  absorption  of  the  sun's  rays  by  the  leaf  raises  the 
temperature  of  the  latter  above  that  of  the  surrounding  medium,  and 
so  quickens  the  process  of  assimilation. 

The  assimilation  of  carbon  dioxide,  the  formation  of  starch,  and 
the  evolution  of  oxygen  will  go  on  in  the  isolated  chloroplast.  In  the 
absence  of  chlorophyll,  as  in  an  etiolated  leaf,  the  formation  of  starch 
will  take  place  if  the  plant  be  supplied  with  a  sugar  such  as  glucose, 
and  this  conversion  represents  the  main  function  of  the  leucoplasts 
present  in  all  the  cells  of  the  reserve  organs  of  plants.  In  the  absence 
of  chlorophyll  no  decomposition  of  carbon  dioxide  takes  place,  so  that 
this  pigment  is  e\adently  essential  for  the  utilisation  of  the  sun's 
energy.  Chlorophyll  may  be  extracted  from  leaves  by  means  of 
absolute  alcohol.  A  solution  is  thus  obtained  which  is  green  by  trans- 
mitted and  red  by  reflected  hght,  i.e.  chlorophyll  is  a  fluorescent 
substance.  It  presents  four  absorption  bands,  the  chief  being  an 
intense  black  band  between  Eraunhofer's  lines  B  and  C.  If  the  chloro- 
phyll is  the  means  of  conversion  of  the  solar  into  chemical  energ}',  the 
conversion  must  take  place  at  the  expense  of  the  light  which  is 
absorbed  by  the  pigment.  One  would  expect,  therefore,  the  process  of 
assimilation  to  be  most  pronounced  in  those  parts  of  the  spectrum 
corresponding  to  the  absorption  bands — an  expectation  which  has  been 
realised  by  experiment. 

As  to  the  exact  chemical  changes  effected  by  these  absorbed  rays 
physiologists  are  still  undecided.  There  can  be  no  doubt  that  an  early 
product  of  the  process  is  a  hexose,  which  is  rapidly  converted  into  cane 
sugar  or  into  starch.  It  was  suggested  by  Baeyer  in  1870  that  carbon 
dioxide  was  reduced  to  formaldehyde,  which  later  by  condensation 
yielded  sugar.  We  know  that  formaldehyde  easily  polymerises  to 
form  a  mixture  of  hexoses,  but  until  recently  no  evidence  had  been 
brought  forward  of  its  presence  as  an  intermediate  product  in  the 
assimilatory  process.  For  most  plants,  indeed,  formaldehvde  is 
extremely  poisonous,  though  certain  algie,  as  well  as  the  water-plant, 
Elodea,  can  stand  a  solution  containing  -001  per  cent,  formakk'hyde. 
Bokorny  stated  that  spirogyra  could  form  starch  out  of  such  deriva- 
tives of  formaldehyde  as  sodium  oxymethyl-sulphonate,  or  from 
methylal.     The  difficulty  in  the.se  cases  is  that  possibly  a  spontaneous 


124  PHYSIOLOGY 

formation  of  sugar  from  the  formaldehyde  had  taken  place  in  the  solu- 
tion and  that  the  plants  were  using  up  the  sugar  rather  than  the  for- 
maldehyde as  the  source  of  their  starch. 

One  must  assume,  with  TimiriazefE,  that  the  function  of  chlorophyll 
in  the  process  of  assimilation  is  that  of  a  sensitiser.  Just  as  the  addition 
of  eosin  to  the  emulsion  used  for  coating  photographic  plates  will 
render  these  sensitive  to  the  red  and  gxeen  parts  of  the  spectrum,  i.e. 
will  excite  change  in  the  silver  salt  when  light  from  these  parts  of  the 
spectrum  falls  upon  it,  so  the  chlorophyll  serves  as  a  means  by  which 
the  absorbed  solar  energy  can  be  utilised  for  the  production  of  chemical 
change  in  the  chloroplast.  Attempts  have  been  made  to  imitate  this 
process  outside  the  plant.  Thus  Bach  passed  a  stream  of  carbon 
dioxide  through  a  1-5  per  cent,  solution  of  a  fluorescent  substance, 
uranium  acetate,  in  sunlight.  As  a  result  there  was  a  precipitate 
of  uranium  oxide  and  peroxide,  with  the  formation  of  traces  of  for- 
maldehyde. Usher  and  Priestley,  on  treating  a  solution  of  carbon 
dioxide  with  1-5  per  cent,  uranium  acetate  or  sulphate  in  bright  sun- 
light, obtained  uranium  peroxide  and  formic  acid,  but  no  formaldehyde. 
The  formation  of  peroxides  in  these  conditions  suggests  that  the  first 
change  in  the  chloroplast  may  be  as  follows  : 

CO.,  +  3H2O  -=  2H2O2  +  CH2O 

Such  a  reaction  must  he  regarded  as  reversible  since  the  hydrogen 
peroxide  first  formed  would  tend  to  oxidise  the  formaldehyde  again. 
Moreover  it  would  have  a  destructive  influence  on  the  chlorophyll 
itself,  which  is  easily  oxidised.  In  order,  therefore,  that  the  reaction 
should  go  on  in  one  direction  only,  i.e.  that  of  assimilation,  means 
must  be  present  in  the  chlorophyll  corpuscles  for  the  removal  of 
both  hydrogen  peroxide  and  formaldehyde  as  soon  as  they  are  formed. 
The  removal  of  the  hydrogen  peroxide  can  be  effected  by  a  catalase, 
which  is  fairly  widely  distributed  in  plants  and  has  been  shown  by 
the  last-named  authors  to  be  present  in  the  chloroplasts.  In  order 
to  demonstrate  the  production  of  the  first  result  of  assimilation,  i.e. 
formaldehyde,  the  further  stages  in  its  conversion  must  be  stopped 
by  killing  the  plant  and  the  catalase  it  contains.  They  therefore 
placed  leaves,  which  had  been  boiled,  in  water  saturated  with  carbon 
dioxide  and  exposed  them  to  bright  sunlight.  The  leaves  were 
bleached  by  the  oxidation  of  the  chlorophyll,  and  some  substance  of  an 
aldehydic  nature  was  produced,  as  shown  by  the  red  colour  obtained  on 
placing  them  in  rosaniline,  previously  decolorised  with  sulphurous  acid. 

Two  proofs  were  brought  forward  that  this  substance  was  formaldehyde : 
(a)  Some  of  the  bleached  leaves  were  soaked  for  twelve  hours  in  aniline 

water.     Tlie  chloroplasts  under  the  microscope  were  seen  to  contain  crystals 

resembling  methylene  aniline. 


THE  MECHANISM  OF  ORGANIC  SYNTHESIS    1:^5 

(Ij)  Tho  leaves  were  distilled  in  a  current  of  steam.  The  distillate  was 
shown  to  contain  formaldehyde  by  the  formation  of  methylene  aniline  crystals 
on  treatment  with  aniline,  and  by  the  preparation  from  it  of  the  characteristic 
tetrabrome  derivative  of  hexamethylenetetraminc. 

Usher  and  Priestley  conclude  that  the  first  products  of  the  photo- 
lysis of  carbonic  acid  are  hydrogen  peroxide  and  formaldehyde.  Both 
these  substances  are  rapidly  removed  from  the  reaction.  The  hydrogen 
peroxide  is  broken  up  by  the  catalase  into  water  and  oxygen  which 
is  turned  out  by  the  plant.  The  formaldehyde  is  at  once  polymerised 
in  the  protoplasm  of  the  chloroplast  with  the  formation  first  of  a 
hexose  and  then  of  starch.  The  formaldehyde,  if  not  removed  in  this 
way,  destroys  the  catalase.  The  hydrogen  peroxide,  if  not  broken 
up  by  the  catalase,  destroys  the  chlorophyll. 

The  relations  between  the  various  factors  in  this  process  may  be 
diagraimuatically  expressed  thus  : 

Carbon  dioxide  +  Water 


(//  not  removed,  destrous)-^      Chlorophyll 


^  ^ ^^ 

Hydrogen  peroxide  +  Formaldehyde 

/ 
Alf  not  removed,  poisons) 

Enzyme  Lfving  protoplasm 

Oxygen  Carbohydrates 

In  thus  reducing  certain  of  the  stages  in  the  assimilation  of  carbon 
to  phenomena  which  can  be  imitated  outside  the  living  organism  we 
have  made  considerable  strides  in  the  '  understanding  '  of  the  pro- 
cess. The  stage  for  which  the  vitality  of  the  chloroplast  is  absolutely 
essential  is  the  formation  of  starch  from  formaldehyde.  Outside  the 
body,  our  polymerisation  of  formaldehyde  results  in  the  formation  of 
a  mixture  of  sugars  which  are  optically  inactive.  The  same  process, 
in  the  living  cell,  leads  to  the  production  of  optically  active  sugars 
which  are  connected  stereochemically  and  mutually  convertible  one 
into  the  other,  e.g.  fructose  and  glucose.  The  derivatives  of  protoplasm, 
containing  asymmetric  carbon  atoms,  are  in  the  same  way  optically 
active,  and  it  seems  that  the  asymmetry  of  the  protoplasmic  molecule 
conditions  a  corresponding  asymmetry  in  the  substance  which  it 
builds  on  to  itself.  The  protoplasm  fm'iiishes,  so  to  speak,  a  mould 
in  which  polymerisation  of  formaldehyde  can  result  only  in  the  produc- 
tion of  sugars  of  certain  definite  stereochemical  configurations. 

Few,  if  any,  chemical  reactions  are  pure.  Nearly  all  are  attended 
with  by-reactions,  so  that  the  yield  of  end  product  never  attains 


12  G  PHYSIOLOGY 

100  per  cent,  of  the  theoretical  yield.  Even  if  the  above  mechanism 
be  regarded  as  the  chief  one,  it  is  probable  that  side  reactions  take 
place  at  the  same  time,  so  that  we  may  have  the  formation  of  sub- 
stances such  as  giyoxylic  acid  and  other  derivatives  of  the  fatty  acid 
series.  Such  by-products  might  play  an  important  part  in  the  other 
synthetic  activities  of  the  cell,  and  especially  in  the  formation  of  fats  and 
proteins. 

THE   FORMATION  OF    PROTEINS 

Our  knowledge  of  the  mechanism  by  which  proteins  are  synthetised 
in  plants  is  still  more  incomplete  than  that  of  the  synthesis  of  carbo- 
hydrates, and  we  are  reduced  in  most  cases  to  a  discussion  of  the  possible 
ways  in  which,  from  our  knowledge  of  the  chemical  behaviour  of  the 
constituents  of  the  protein  molecule,  we  might  conceive  of  its  forma- 
tion. We  can  at  any  rate  state  the  problems  which  have  to  be  solved 
and  study  the  conditions  under  which  the  synthesis  of  protein  is 
possible  in  plants  and  in  animals. 

We  know  that  plants  are  independent  of  any  organic  food  for 
building  up  their  various  constituents,  whether  carbohydrate,  protein, 
or  fat,  provided  only  that  they  possess  chlorophyll  corpuscles  and  vso 
are  able  to  utilise  the  energy  of  the  sun's  rays.  Most  plants  will  grow 
in  the  dark  if  suppHed  with  sugar  and  with  combined  nitrogen  either 
in  the  form  of  ammonia  or  of  nitrates.  The  higher  plants  are  especially 
dependent  on  the  presence  of  nitrogen  in  the  latter  form,  and  it  is  on 
this  accomit  that  the  nitrifying  bacteria  of  the  soil  acquire  so  gxeat 
an  importance  for  agriculture.  From  the  carbon  dioxide  of  the  atmo- 
sphere or  from  the  hexose  formed  by  the  assimilation  of  carbon,  and 
from  nitrogen,  in  the  form  either  of  ammonia  or  nitrates,  together 
with  inorganic  sulphates,  the  plant  cell  is  able  to  build  up  all  the 
various  types  of  protein  which  are  distributed  throughout  the  vegetable 
kingdom.  Our  study  of  the  disintegxation  products  of  proteins  has 
shown  that  this  class  of  bodies  contains  a  large  number  of  the  most 
diverse  groups,  having  as  a  common  character  the  possession  of 
nitrogen  in  their  molecule,  generally  as  an  NHg  or  NH  gToup.  These 
disintegration  products  can  be  classified  as  follows  : 

(a)  Open  chain  amino-acids. 

(6)  Heterocyclic  compounds;  including  : 

(1)  Pyrrol  derivatives. 

(2)  Pyrimidine  derivatives. 

(3)  Tminazol  derivatives. 

These  two  last  groups  co- exist  in  all  the  purine  compounds. 

(c)  Benzene  derivatives. 

(d)  Indol  derivatives. 

The  first  step  in  the  synthesis  of  proteins  is  probably  the  formation 


THE  MECHANISM  OE  ORGANIC  SYNTHESIS  127 

of  these  constituent  groups.  Just  as  in  digestion  the  protein  mole- 
cule is  taken  to  pieces  with  the  formation  of  the  different  amino-acids, 
so  in  the  synthetic  action  of  protoplasm  the  reverse  process  of  dehy- 
dration occurs,  resulting  in  a  coupling  up  of  the  different  groups,  as  has 
been  effected  by  Fischer  in  the  case  of  the  polypeptides.  Wherever 
transport  of  protein  from  one  part  of  the  organism  to  another  is 
necessary  the  protein  is  carried,  not  in  its  original  form,  but  in  the 
hydrolysed  condition  of  amino-acids.  Thus  the  germination  of  seeds 
which  contain  rich  stores  of  protein  is  accompanied  b}"  a  liberation 
of  proteolytic  ferments  within  the  cells  of  the  seeds,  and  the  break- 
down of  the  reserve  protein  into  its  constituent  amino-acids.  As 
amino-acids  it  is  transported  into  the  growing  tip  and  leaves  of  the 
seedling,  analysis  of  the  latter  showing  a  very  large  percentage  of 
nitrogen  in  the  form  of  amino-acids.  This  is  especially  the  case  if 
the  synthetic  functions  of  the  growing  tip  are  hindered  by  inter- 
ference with  assimilation,  as,  e.g.  by  keeping  the  plant  in  the  dark. 
Under  these  circumstances,  asparagine  may  form  as  much  as 
25  per  cent,  of  the  total  dried  weight  of  the  seedling.  In  animals 
the  greater  part  of  the  protein  of  the  food  is  broken  down  into  its 
constituent  amino-acids  in  the  intestine.  These  are  absorbed  and 
probably  carried  to  the  different  organs  of  the  body,  w^here  they 
are  resynthetised,  generally  in  different  proportions  from  those  that 
obtained  in  the  original  protein,  into  the  protein  specific  for  the  organ 
or  tissue.  The  same  process  of  hydrolysis  and  subsequent  synthesis 
occurs  whenever  the  transport  of  protein  is  necessary  from  one  organ 
to  another.  We  shall  later  on  have  to  discuss  the  possibihty  of 
synthesis  of  the  different  amino-acids  in  animals.  We  need,  therefore, 
at  present  only  deal  with  the  possible  methods  by  which,  from  the 
glucose  or  substances  produced  in  the  assimilation  of  carbon  and  from 
the  ammonia  or  nitrates  derived  from  the  soil,  the  plant  is  able  to  make 
the  different  groups  which  go  to  the  building  up  of  the  protein  molecule. 
All  the  amino-acids  contain  the  NHg  group  in  the  a  position.  We 
can  therefore  consider  them  as  formed  by  the  interaction  of  an 
a-oxyacid  and  ammonia.     Thus  : 

CH3  CH3 

CH .  OH  +  NH  3       =         CH .  NH.  +  H.,0 

COOH  COOH 

lactic  acid  alanine 

This  particular  example,  namely,  the  formation  of  alanine,  may  occur 
at  the  expense  of  the  glucose  produced  as  the  first  product  of  assimila- 
tion of  carbon  dioxide.     If  a  solution  of  glucose  together  with  lime  be 


128 


PHYSIOLOGY 


exposed  to  sunlight  for  a  considerable  time  it  undergoes  decomposition 
with  the  formation  of  lactic  acid.     Thus  : 


^6^12^6 


2C3He03 
lactic  acid 


glucose 

This  change  of  glucose  to  lactic  acid  under  the  catalytic  nifluence 
of  the  alkaline  calcium  hydrate  probably  occurs  by  means  of  a  shifting 
of  the  elements  of  the  water,  a  process  which  in  many  long  chains 
seems  to  occur  with  considerable  facility,  and  is  dependent  on  the 
spatial  configuration  of  the  molecule  involved.  Thus  the  change  of 
sugar  to  lactic  acid  is  readily  effected  by  means  of  many  micro- 
organisms in  the  case  of  glucose,  fructose,  and  mannose,  but  with 
considerable  difiiculty  in  the  case  of  galactose.  In  the  three  former 
sugars  the  atoms  round  the  two  middle  carbon  atoms  of  the  chain 
are  disposed  thus  : 


OH.C.H 
H.C.OH 


or 


H.C.OH 

I 
OH.C.H 


When  either  of  these  arrangements  reacts  with  water,  thus  : 


CH2OH 
CHOH 
OH.C.H  OH 


HCOH 
CHOH 


H 


CH2OH 


CHOH 
COH  +  H2O 

CH.OH 
CHOH 


COH  COH 

we  obtain  two  molecules  of  glyceric  aldehyde,  which  then  by  a  further 
shifting  of  the  OH  and  H  groups  becomes 

CH3 

I 
I 
CH.OH 


COOH 

lactic  acid 


Lactic  acid  with  ammoiiia  and  some  dehydrating  agent  will  give  amino- 


THE  MECHANISM  OF  ORGANIC  SYNTHESIS  129 

propionic  acid  or  alanine.  The  formation  of  the  higher  amino-acids 
involves  a  process  of  reduction  of  the  sugar  first  formed  in  the  chloro- 
phyll granules.  It  is  possible,  however,  that  the  starting-point  for  the 
amino-acid  synthesis  may  be,  not  a  hexose  itself,  but  some  other  sub- 
stances, formed,  so  to  speak,  as  by-products  in  the  assimilation  of  sugar 
from  carbon  dioxide.  We  have  seen  reason  to  believe  that  the  first 
result  of  the  action  of  the  sun's  rays  within  the  chlorophyll  corpuscle 
is  formaldehyde.  This  substance  in  the  presence  of  calcium  carbonate 
when  exposed  to  the  light  gives  a  mixture  of  glyceryl  aldehyde  and 
dihydroxy acetone.  If  we  can  assume  that  acetone  is  formed  from  the 
latter  by  a  process  of  reduction,  we  might  possibly  derive  leucine  from 
an  interaction  of  this  substance  \\-ith  lactic  acid  and  ammonia.     Thus  : 

CH3       CH3 
CH,     CTI3  Ch/ 

CO  +CH.OH  +  NH3  +  H.,        =       CH.       -f2H20 

II  I 

CH3     COOH  CH.NH, 

COOH 

As  an  intermediate  product  in  the  synthesis  of  starch,  glyoxylic  acid 

CHO 

I  has  been  described  as  occurring  in  the  green  parts  of  plants. 

COOH 

This  substance  with  ammonia  gives  formyl  glycine,  and  by  the  splitting 
ofE  of  formic  acid,  glycine  or  amino-acetic  acid.  Why  nitrates  are 
necessary  for  certain  forms  of  plants  is  not  at  present  understood.  In 
the  proteins  nitrogen  always  occurs  in  an  unoxidised  form  as  NH  or 
NH2,  and  the  nitrates  taken  up  from  the  soil  must  therefore  undergo 
reduction  before  they  can  be  built  into  the  protein  molecule.  It  is 
supposed  that  they  may  pass  through  a  series  of  reductions,  namely  : 

HNO3  HNO2  HNO  H2N— OH 

nitric  acid  nitrous  acid       hyponitrous  acid  hydroxylamine 

and  that  the  latter  substance  then  reacts  with  formaldehyde  or  other 
substance  derived  from  the  carbon  dioxide  assimilation  to  form  amino- 
compounds.  In  general  we  may  say  that  the  probable  mechanism 
of  formation  of  amino-acids  is  the  production  of  a-oxyacids,  which  then 
react  with  ammonia  to  form  the  amino-acids  of  the  protein  molecule  ; 
but  of  the  exact  steps  in  this  process  we  are  at  present  ignorant. 
Knoop's  work  would  point  to  the  ketonic  acids  as  forming  one  step, 
and  as  interacting  with  ammonia,  with  simultaneous  reduction,  to 
form  amino-acids. 

9 


130  PHYSIOLOGY 

The  Pyrrol  Ring  which  occurs  in  proline  and  in  oxyproline 
may  possibly  be  derived  from  an  open  chain  amino-acid,  and  it  has, 
in  fact,  been  suggested  that  the  proline  found  in  the  products  of  the  acid 
digestion  of  proteins  is  derived  from  ornithine  by  a  process  of  con- 
densation with  the  loss  of  ammonia.     Thus  : 

CH2NH2 .  CH2 .  CH, .  CH .  NH2COOH  becomes 
CH2.CH2.CH2.CH.COOH 


NH 

or,  as  it  is  generally  written  : 


CH2 — CH2 

CH2    CH.COOH 

\/ 
NH 

Its  pre-existence  in  the  protein  molecule  is,  however,  practically 
assured,  and  it  plays  an  important  part  in  the  building  up  both  of 
chlorophyll  and  of  hsematin,  the  prosthetic  group  of  haemoglobin. 

CH— NH. 
Iminazol  ||  ^^JH 

CH— N 

occurs  in  histidine  (which  is  iminazol  alanine),  and  can  be  formed 
fairly  readily  by  the  action  of  certain  catalytic  agents  on  a  mixture  of 
glucose  and  ammonia.  Thus,  if  a  solution  of  glucose  with  ammonia 
and  zinc  oxide  be  exposed  to  light,  methyl  iminazol  is  formed  in 
large  quantities.  Windaus  and  Knoop  imagined  that  in  this  process 
glyceric  aldehyde  and  formaldehyde  are  first  formed,  and  that  these 
then  interact  with  ammonia  to  form  methyl  iminazol. 

CH3 

C    — NH 

II  JOK 

CH— N    ^ 

It  is  interesting  to  note  that  if  we  attach  to  this  compound  carbamide 
or  urea  we  obtain  a  body  belonging  to  the  class  of  purines.  Xanthin, 
for  instance,,  would  have  a  formula 

NH-CO 

CO     C— NH 

I         II  >H 

NH— CH— N 


THE  MECHANISM  OF  ORGANIC  SYNTHESIS  131 

Thus  by  the  action  of  simple  catalytic  agencies  on  sugar  and  ammonia 
we  can  obtain  the  iminazol  nucleus,  and  by  easy  transitions  pass  through 
this  to  the  purine  nucleus  with  its  contained  ring,  the  pyrimidine 
nucleus,  found  in  the  bases  cytosine,  uracil,  &c.,  which  occur  in  the 
nucleins. 

With  regard  to  the  formation  of  the  aromatic  constituents  of  the 
protein  molecule,  i.e.  those  containing  the  benzene  and  indol  rings, 
we  have  at  present  very  little  indication  even  of  the  lines  along  which 
it  might  be  possible  to  prosecute  our  researches.  It  has  been  suggested 
that  inosite  may  represent  some  stage  in  the  formation  of  the  benzene 
ring  from  the  open  chain  found  in  the  carbohydrates.  Inosite  has 
the  same  formula  as  glucose,  namely,  CeHjjOe,  but  is  a  saturated  ring 
compound  : 

CHOH 


CHOH 
CHOH 


CHOH 
CHOH 


CHOH 

and  may  be  expected  to  be  formed  as  a  result  of  polymerisation  of 
formaldehyde.  We  have  no  evidence,  however,  of  the  possibility  of 
such  a  formation,  and  the  relations  of  this  substance  with  the  benzene 
compounds  are  by  no  means  intimate.  It  is  of  such  universal  occm- 
rence,  both  in  plants  and  animals,  that  it  is  difficult  to  refrain  from  the 
suspicion  that  it  may  play  some  part  as  an  intermediate  stage  between 
the  fatty  and  the  aromatic  series. 

Since  plants  are  able  to  manufacture  all  these  varied  substances  out 
of  the  products  of  assimilation  of  carbon  and  ammonia  or  nitrates, 
they  must  also  find  no  difficulty  in  transforming  one  amino-acid  into 
another,  and  we  know  that  most  plants  can  procure  their  nitrogen 
from  a  solution  of  a  single  amino-acid  as  well  as  from  a  nutrient  fluid 
containing  the  nitrogen  in  the  form  of  ammonia.  In  animals  the 
power  of  transforming  one  amino  acid  into  another,  of  one  group 
into  another,  is  probably  strictly  limited.  So  far  as  we  know,  nearly 
all  the  amino-acids  utilised  in  the  building  up  of  the  animal  proteins 
are  derived  directly  from  those  contained  in  the  food.  On  the  other 
hand,  we  have  evidence  in  the  animal  body  of  synthesis  of  the  purine 
bodies,  and  therefore  of  the  pyrimidine  and  iminazol  rings.  The  hen's 
egg  at  the  beginning  of  incubation  contains  very  little  nuclein, 
nearly  the  whole  of  its  phosphorus  being  present  in  the  form  of  phos- 
phoproteins  and  lecithin.  As  incubation  proceeds  these  substances 
disappear,  their  place  being  taken  by  the  nucleins  which  form  the  chief 
constituent  of  the  nuclei  of  the  developing  chick.  In  the  same  way  the 
ovaries  and  testes  of  the  salmon  are  formed  during  their  sojourn  in 


132  PHYSIOLOGY 

fresh  water  at  the  expense  of  the  skeletal  muscles,  especially  those  of 
the  back.  Here  again  there  is  a  transformation  of  a  tissue  poor  in 
purine  bases  into  a  tissue  which  consists  almost  exclusively  of  nucleins 
and  protamines.  Whether  in  this  case  there  is  a  direct  conversion  of  the 
mono-amino-acids  of  the  muscle  proteins  into  the  diamino-acids  and 
bases  typical  of  protamines,  we  do  not  know.  It  is  more  probable 
that  only  diamino-acids  and  bases  previously  existing  in  the  muscle 
are  utihsed  for  the  formation  of  the  generative  glands,  the  other  amino- 
acids  being  oxidised  and  utilised  for  the  ordinary  energy  requirements 
of  the  animal. 

THE   SYNTHESIS   OF  FATS 

In  some  plants  fat  globules  have  been  stated  to  appear  as  the  first 
products  of  the  assimilation  of  carbon  dioxide  under  the  influence 
of  sunlight,  but  there  is  no  doubt  that  as  a  rule  the  formation 
of  fats  as  reserve  material  in  seeds  or  fruits  occurs  at  the  expense 
of  carbohydrates.  In  the  higher  animals,  too,  although  a  certain 
amount  of  the  fat  of  the  body  is  derived  from  the  fat  taken  up 
with  the  food,  the  organism  can  also  manufacture  neutral  fat 
out  of  the  carbohydrates  presented  to  it  in  its  food.  The  problem, 
therefore,  of  the  s}Tithesis  of  the  fats  is  the  problem  of  the  conversion 
of  a  sugar  such  as  glucose  into  glycerin  and  the  fatty  acids.  Although 
this  conversion  is  apparently  so  easily  effected  by  the  living  organism, 
it  is  one  which  from  the  chemical  standpoint  involves  considerable 
difficulties.  On  account  of  the  fact  that  the  higher  fatty  acids  con- 
sist largely  of  oleic  and  stearic  acids,  i.e.  acids  containing  eighteen 
carbon  atoms  in  their  chain,  it  has  been  thought  that  the  synthesis 
might  be  brought  about  by  the  linking  together  of  three  molecules  of 
a  hexose.  Such  a  change  would  involve  a  series  of  difficult  chemical 
transformations.  For  instance,  no  less  than  sixteen  out  of  the  eighteen 
oxygen  atoms  present  in  the  three  glucose  molecules  would  have 
to  be  dislodged  in  order  to  convert  the  chain  into  stearic  acid. 
Moreover,  although  these  two  acids  contain  a  multiple  of  six  carbon 
atoms,  a  whole  array  of  fats  are  found  both  in  plants  and  animals 
which  could  not  be  derived  by  a  simple  aggregation  of  glucose  mole- 
cules, and  it  is  worthy  of  note  that,  of  all  the  fatty  acids  which  occur 
in  nature,  all  those  with  more  than  five  carbon  atoms  contain  an  even 
number  of  carbon  atoms.  Thus  in  milk,  in  addition  to  the  three  com- 
mon fats,  tristearin,  tripalmitin,  and  triolein,  we  find  the  glycerides 
of  caproic,  capryUic,  capric,  lauric,  and  myristic  acids,  i.e.  acids  with 
6,  8,  10,  12,  and  14  carbon  atoms.  In  all  cases  these  acids  are  the 
normal  acids  with,  straight  unbranched  chains.  It  seems  probable 
that  in  the  transformation  of  carbohydrate  into  fatty  acid  the  latter 
is  built  up,  not  by  six  carbon  atoms,  but   by  two  carbon  atoms  at  a 


THE  MECHANISM  OF  ORGANIC  SYNTHESIS 


133 


time.  It  has  been  suggested  by  Magnus  Lev}'  and  by  Leathes  that 
the  transformation  may  occur  by  way  of  lactic  acid.  We  have  seen 
already  that  glucose  and  the  sugars  of  analogous  composition  may 
be  converted  under  the  influence  either  of  sunlight  or  of  micro- 
organisms into  lactic  acid.  Lactic  acid  breaks  down  with  readiness 
into  aldehyde  and  formic  acid. 


CH, 


CH, 


CHOH    =        CHO  +  H 

I  I 

COOH  COOH 

Aldehyde  undergoes  condensation  to  form  aldol. 


CH. 


CH, 


CHO 


aldehyde 


CHOH 

I 

I 
CHO 

aldol 


Aldol  reacts  with  water  and  midergoes  a  shifting  of  its  OH  and  H 
groups,  in  a  manner  with  which  we  are  already  familiar  as  occurring 
in  the  conversion  of  glucose  into  lactic  acid,  forming  butyric  acid. 
We  may  represent  the  reaction  in  the  following  way,  placing  the  water 
molecules  opposite  those  groups  of  the  aldol  molecule  with  which  they 
react  : 

CH, 


H      HO  CH 


gives 


H 


CH2 
OH         OCH      OH 

CH, 


CH2 

CH, 

I 
COOH 


+  2H,0 


134  PHYSI0L0C4Y 

It  will  be  seen  that  although  water  must  enter  into  the  reaction  there 
is  no  addition  of  water  to  the  aldol  in  order  to  form  the  butyric  acid. 

It  has  been  suggested  that  similar  reactions  might  account  for  the 
formation  of  the  higher  fatty  acids,  in  which  case  one  molecule  of 
acetic  aldehyde  would  be  added  to  the  fatty  acid  in  order  to  build  up 
the  acid  which  is  next  highest  in  the  series.  Although  certain  of  the 
higher  acids  have  been  prepared  in  this  way,  proof  is  still  wanting  that 
a  continuous  series  of  syntheses  may  be  efiected  by  the  continuous 
addition  of  aldehyde.  Such  a  hypothesis  is,  however,  more  probable 
than  the  direct  conversion  of  three  molecules  of  sugar  into  one  molecule 
of  stearic  acid.  The  latter  change  would  be  associated  with  a  very 
great  absorption  of  energy,  whereas  a  continuous  building  up  of  fatty 
acids  by  the  addition  of  aldehyde  obtained  through  lactic  acid  from  the 
disintegration  of  hexose  molecules  only  requires  a  small  expenditure  of 
energy,  which  could  be  obtained  by  the  combustion  of  the  formic  acid 
formed  as  a  by-product  in  the  process.  If  we  suppose  that  the  syn- 
thesis of  the  higher  fatty  acids  from  sugar  is  carried  out  in  this  way, 
the  energy  equations  would  be  as  follows  (Leathes)  : 

1  g.  mol.  glucose       )  f2g.  mols.  aldehyde  +  2  g.  mols.  formic  acid. 

677-2  cals.  /       ^[  2  x  275-5  +  2  x  61-7 

=  674-4  cals. 

2  g.  mols,  aldehyde  )  (^  g-  i"ol.  aldol      )  (I  g.  mol.  butvTic  acid. 

-  551  cals.  j~'^[         546-8  cals.     j       ^\         517-8  cafs. 

Or,  tracing  the  same  change  on  as  far  as  palmitic  acid: 

4  g.  mols.  glucose     )  (I  g.  mol.  palmitic  acid  +  8  g.  mols.  formic  acid. 

2708  cals.  J"      ^  \^         2362  cals.  +  494  cals. 

-=  2856  cals. 

In  the  first  stage  of  the  synthesis,  the  reaction  leading  to  butyric  acid, 
the  net  result  would  be,  supposing  the  formic  acid  to  be  oxidised,  that 
some  160  calories,  or  nearly  25  per  cent,  of  the  w^hole  energy,  would  be 
rendered  available  for  other  purposes.  In  the  latter  stages  leading 
to  palmitic  acid  some  of  the  energy  derived  from  the  oxidation  of  the 
formic  acid  would  be  required  for  effecting  the  synthesis,  and  only  about 
12-5  per  cent,  of  the  original  amount  contained  in  the  sugar  would  be 
set  free.  It  is  worth  noting  that  in  the  butyric  fermentation  of  sugar 
by  micro-organisms  there  is  a  production  first  of  lactic  acid,  and  this 
substance  then  disappears  to  give  place  to  butyric  acid.  At  the  same 
time  carbonic  acid  and  hydrogen  are  evolved,  both  gases  being  derived 
from  the  decomposition  of  the  formic  acid.  In  the  process  a  certain 
amount  of  caproic  acid  is  always  produced,  and  the  crude  butyric  acid 
of  fermentation  is  used  as  the  source  from  which  commercial  caproic 
acid  is  derived. 

The  glycerin  which  enters  into  the  formation   of  the  ordinary 


THE  MECHANISM  OF  ORGANIC  SYNTHESIS  135 

neutral  fats  can  be  synthetised  by  both  plants  and  animals,  and  there 
is  every  ground  for  believing  that  it,  like  the  fatty  acids,  may  be 
derived  from  carbohydrates.  We  have  already  seen  that  in  the  con- 
version of  glucose  into  lactic  acid  the  first  step  is  the  formation  of 
glyceric  aldehyde, 

CH2OH  CH2OH 

I  I 

CHOH    •  CHOH 

I  I 

CHOH  OHO 


CHOH  CH2OH 

CHOH  CHOH 

I  I 

CHO  CHO 

and  it  is  easy  to  understand  how  by  a  process  of  reduction  the  alde- 
hyde is  converted  into  the  corresponding  alcohol,  namely,  glycerin. 
The  synthesis  of  the  neutral  fat  from  glycerin  and  fatty  acid  is  a  change 
which  can  be  accomplished  by  many  ferments.  It  is  one  involving 
practically  no  absorption  or  expenditure  of  energy.  The  change  is  a 
reversible  one,  and  we  find  both  in  plants  and  animals  that  a  hydroiysia 
of  neutral  fat  into  fatty  acid  and  glycerin  always  occurs  when  a  trans- 
port of  the  fat  is  required,  while  the  laying  dovrn  of  fat  as  a  store  of 
energy  is  always  preceded  by  a  resynthesis  of  the  neutral  fat.  We 
shall  have  occasion  to  deal  in  greater  detail  with  these  questions  when 
we  have  to  discuss  the  formation  and  fate  of  the  fat  in  the  animal 
body. 


CHAPTER  IV 
THE  ENERGETIC  BASIS  OF  THE   BODY 

SECTION  I 

THE  ENERGY  OF  MOLECULES  IN  SOLUTION 

Every  vital  act  involves  at  the  same  time  a  transformation  of  the 
material  basis  of  the  living  cell  and  a  transformation  of  energy.  The 
ultimate  source  of  the  energies  displayed  by  the  animal  organism  is  to 
be  sought  in  the  chemical  energy  of  the  substances  taken  in  as  food. 
In  all  the  changes  undergone  by  either  matter  or  energy  in  the  body 
there  is  neither  destruction  nor  creation.  The  living  organism  may 
therefore  be  regarded  in  one  sense  as  a  machine,  that  is  to  say,  a 
system  for  the  conversion  of  one  form  of  energy  into  another.  Thus 
the  steam-engine  converts  the  potential  energy  of  overheated  steam 
into  mechanical  work  ;  a  gas-engine  the  chemical  energ)^  of  an  explo- 
sive mixture  of  gases  into  heat  and  mechanical  energy  ;  in  a  battery 
there  is  a  transformation  of  chemical  into  electrical  energy  ;  in  a 
dynamo,  of  mechanical  into  electrical  energy,  and  so  on.  In  the  living 
cell  the  chemical  energy  of  the  food  may  undergo  conversion  into 
any  of  the  other  forms  mentioned  above,  i.e.  heat,  work,  electrical 
difference  of  potential,  or  it  may  be  used  for  the  production  of 
other  chemical  substances  possessing  perhaps  as  much  potential 
energy  as  or  more  than  the  food-stuffs"  themselves. 

The  protoplasm,  which  is  the  seat  of  all  these  changes  in  both 
plants  and  animals,  is  active  only  within  fairly  narrow  limits  of  tem- 
perature, approximately  between  5°  and  40°  C.  In  consistence  it  is 
slimy  and  wet,  water  forming  from  70  to  95  per  cent,  of  its  bulk. 
No  substance  introduced  into  the  protoplasm  has  any  influence  on  it, 
unless  it  be  soluble,  and  the  first  stage  in  the  preparation  of  food-stuffs 
for  assimilation  always  consists  in  a  process  of  solution.  The  sole 
source  of  energy  to  the  body  being  that  conveyed  with  the  food,  it 
follows  that  all  the  energy  with  which  we  have  to  deal  is  the  energy 
of  molecules  in  watery  solution,  the  playground  of  whose  activities  is 
a  jelly-like  mass  of  colloidal  material,  heterogeneous  yet  structurally 
continuous.  It  is  important,  therefore,  at  the  outset  to  inquire  into 
the  nature  of  this  energy  and  the  methods  by  which  it  may  be  measured. 

136 


H 


THE  ENERGY  OF  MOLECULES  IX  SOLUTION         137 

OSMOTIC  PRESSURE.  If  we  place  two  gas  jars  together,  mouth 
to  mouth,  as  in  Fig.  19,  the  upper  jar  containing  hydrogen  and  the 
lower  jar  some  heavier  gas,  such  as  oxygen  or  carbon  dioxide, 
within  a  very  short  time  the  gases  will  have  become  intimately 
mixed,  and  each  jar  will  contain  an  equal  amount  of  both  gases.  We 
say  that  each  gas  has  diffused  into  the  other,  and  ascribe  the  diffusion 
to  the  movement  of  the  gaseous  molecules.  In  closed  vessels  the 
rapidly  moving  molecules  are  continually  impinging  on 
the  walls  of  the  vessels  and  rebounding,  and  it  is  this 
bombardment  by  the  gaseous  molecules  which  is  respon- 
sible for  the  pressure  exerted  by  a  gas  on  its  containing 
walls.  If  we  double  the  amount  of  gas  in  a  given  space, 
we  double  the  amount  of  molecules  which  strike  a  unit 
area  of  the  wall  in  unit  time,  and  therefore  double  the 
pressure  exerted  by  the  gas  on  the  vessel  wall.  In  this 
way  we  may  explain  the  law  of  Boyle  that  the  pressure 
of  a  gas  is  inversely  proportional  to  its  volume,  or  the 
product  of  pressure  and  volume  at  a  given  temperature 
is  a  constant,  PV  =  C,  or  since  the  energy  of  the  mole- 
cules is  proportionate  to  the  absolute  temperature, 
PV  =  RT,  the  familiar  gas  equation. 

The  molecules  of  substances  in  solution  behave.' 
within  the  limits  of  the  solution,  in  a  manner  precisely- 
similar  to  the  free  molecules  of  a  gas.  Thus,  if  a  vessel 
be  half  filled  with  a  10  per  cent,  solution  of  sugar  and 
be  then  filled  up  by  carefully  pouring  distilled  water, 
so  as  to  form  a  distinct  layer  on  the  heavier  sugar 

solution,  the  sugar  at  once  begins  to   move    upwards     ''"^ ^ 

into    the    distilled    water.      In    consequence    of    the  Fio.  \'j. 

resistance  offered  to  the  movement  of  the  sugar 
molecules  through  the  water,  this  process  of  diffttsion  is  slow,  but  if 
the  vessel  be  left  undisturbed  and  free  from  any  agitation  for  two 
or  three  months  the  sugar  will  be  found  to  spread  gradually  throughout 
the  liquid,  so  that  at  the  end  of  this  time  all  parts  of  the  fluid  contain  a 
uniform  amount  of  sugar. 

This  process  of  diffusion,  like  that  of  gases,  must  be  ascribed  to  a 
continuous  translatory  movement  of  the  dissolved  molecules.  Since 
the  molecules  possess  mass  and  are  endowed  with  a  velocity,  it  is 
evident  that  they  can  exercise  a  pressure  on  any  membrane  or  dividing 
surface  which  tends  to  hinder  their  free  passage  within  the  limits  of  the 
solvent.  Thus  if  we  take  a  pig's  bladder  containing  a  20  per  cent, 
solution  of  dextrose  and  immerse  it  in  distilled  water,  water  will  pass  in 
and  distend  the  bladder  to  such  an  extent  that  it  may  burst  from  the 
rise  of  pressure  in  its  interior.    This  swelling  of  the  bladder  is  due  to 


CO. 


138  PHYSIOLOGY 

the  fact  that  the  molecules  of  sugar  pass  through  it  only  with  diffi- 
culty, and  therefore  in  their  passage  outwards  towards  the  confines 
of  the  water  exert  a  pressure  on  the  walls,  driving  them  apart  and  so 
causing  a  distension  of  the  bladder.  It  is  impossible,  however,  by  this 
means  to  obtain  the  full  osmotic  pressure  due  to  the  pressure  exerted 
by  the  sugar  molecules,  since  the  bladder  wall  itself  is  not  absolutely 
impermeable  to  sugar.  If  we  imagine  the  sugar  solution  confined  in  a 
cylinder  and  covered  with  a  layer  of  distilled  water,  the  movement  of 
the  sugar  molecules  will  cause  them  to  wander  from  the  lower  to  the 
upper  part,  and  this  process  of  diffusion  will  cease  only  when  the 
concentration  has  become  the  same  in  all  parts  of  the  solution.  Sup- 
posing, however,  the  two  fluids  are  separated  by  a  piston,  p  (Fig.  20), 
which  is  '  serai- permeable,'  i.e.  allows  free  passage  to  water,  but  not  to 
the  dissolved  sugar,  the  molecules  of  sugar  will  now  exert  a 
pressure  on  the  piston  similar  to  that  exerted  on  the  walls 
of  the  containing  vessel,  and  will  tend  to  drive  it  upwards. 
The  force  which  it  is  necessary  to  apply  to  the  piston  to 
prevent  its  upward  movement  will  be  the  measure  of  the 
osmotic  pressure  of  the  sugar  in  the  solution.  If  the  piston 
be  pressed  down  with  a  greater  force,  the  sugar  molecules 
alone  are  pressed  together,  since  water  can  pass  freely 
through  the  surface  of  the  piston,  and  the  sugar  solution 
Fig.  20=  is  therefore  rendered  more  concentrated.  Since  force 
must  be  applied  to  the  piston  in  order  to  press  it  down, 
work  is  done  in  the  process,  so  that  the  concentration  of  any  solution 
involves  the  performance  of  an  amount  of  work  determined  by  the 
initial  and  final  osmotic  pressures  of  the  solution.  If,  on  the  other 
hand,  a  weight  be  applied  to  the  piston  which  is  less  than  the  osmotic 
pressure  exerted  by  the  sugar  solution,  the  piston  with  its  weight  will 
be  moved  upwards,  and  the  solution  will  undergo  dilution  until  its 
osmotic  pressure  exactly  balances  the  weight  on  the  piston.  We  see 
that  the  osmotic  pressure  of  a  solution  represents  a  certain  amount 
of  potential  energy,  which  can  be  utilised  in  an  osmotic  machine,  such 
as  that  represented  in  the  diagram,  for  the  performance  of  work. 

THE  MEASUREMENT  OF  THE  OSMOTIC  PRESSURE.  By  a 
method  differing  but  little  from  the  one  just  sketched  out,  Pfeffer 
succeeded  directly  in  measuring  the  osmotic  pressure  of  certain  solu- 
tions. For  this  purpose  Pfeffer  took  advantage  of  the  fact,  discovered 
by  Traube,  that  various  precipitates,  if  deposited  in  the  form  of  mem- 
branes, were  impermeable  to  the  substances  producing  them  as  well 
as  to  some  other  dissolved  substances,  though  allowing  a  free  passage 
of  water.  Thus,  if  a  drop  of  a  concentrated  solution  of  potassium  ferro- 
cyanide  suspended  to  a  glass  rod  be  introduced  carefully  into  a  more 
dilute  solution  of  copper  sulphate,  it  will  be  observed  that   at  the 


THE  ENERGY  Oh'  MOLECULES  IX  SOU'TION 


130 


junction  of  the  drop  and  the  surrounding  fluid  there  is  a  brown  mem- 
branous precipitate  of  copper  ferrocyanide.  In  consequence  of  the 
greater  concentration  of  the  fluid  in  the  drop,  a  constant  passage  of 
water  takes  place  from  without  inwards  through  the  membrane,  and 
the  drop  therefore  grows  continually  in  size,  sometimes  sending  out 
branches  as  a  result  of  slight  currents  in  the  fluid  set  up  by  accidental 
vibrations.  Sugar  introduced  into  such  a  drop,  although  quickening 
its  rate  of  growth,  does  not  pass  out  into  the  surrounding  copper 
sulphate  solution,  nor  is  there  any  passage  of  copper  sulphate  inwards 
or  potassium  ferrocyanide  outwards.  Pfeffer  conceived  the  idea  of 
depositing  such  a  semi-permeable  membrane  within  the  interstices 
of  a  clay  cell.  Strengthened  in  this  way,  it  is  able  to  afford  a  resistance 
to  pressure,  and  therefore  to  permit  of  the  contained  fluid  reaching 
its  full  osmotic  pressure.  For  this  purpose  a  porous  jar  carefully 
cleansed  and  containing  a  solution  of  sugar  mixed  with  a  little  copper 
sulphate  is  dipped  into  a  weak  solution  of  potassium  ferrocyanide.  A 
semi-permeable  membrane  of  copper  ferrocyanide  is  thus  produced 
in  the  pores  of  the  filter,  and  this,  while  allowing  the  passage  of  water, 
is  impermeable  to  the  sugar.  The  tube  is  then  fitted  with  a  cork 
provided  with  a  closed  mercurial  manometer  and  is  immersed  in  distilled 
water,  when  it  is  found  that  water  passes  into  the  cell  until  the  pressure 
within  the  latter  is  equal  to  the  osmotic  pressure  of  the  dissolved 
substances.  By  this  means  Pfeffer  obtained  the  following  results  with 
a  1  per  cent,  solution  of  cane  sugar  at  different  temperatures  : 


Temp.  -C. 

Pressure  in  atmospheres 

Calculated. 

6-8 
13-7 
22-0 
32-0 
360 

Atm. 
0-664 
0-691 
0-721 
0-716 
0-746 

Atm. 

0-665 
0-681 
0-701 
0-725 
0-735 

It  is  always  possible  to  calculate  the  pressure  of  a  gas  when 
its  nature,  its  mass,  and  its  volume  are  known.  By  Avogadro's 
hypothesis,  equal  volumes  of  gases  at  the  same  pressure  contain 
equal  numbers  of  molecules.  On  this  account  the  molecular  weight 
of  any  gas  can  be  reckoned  directly  from  its  density.  The  figures 
obtained  by  Pfeffer  show  that  the  same  laws  apply  to  the  osmotic 
pressure  of  substances  in  solution  as  to  the  pressure  of  gases  in  their 
free  state.    It  is  therefore  possible  to   reckon    the   osmotic   pressure 


140  PHYSIOLOGY 

which  would  be  exerted  by  1  per  cent,  sugar  in  solution  at  a  given 
temperature. 

This  calculation  is  carried  out  as  follows  :  A  gramme  molecule  of  any  gas  at 

0°  C.  and  760  mm.  Hg  has  a  volume  of  22-4  litres,  therefore  342  grammes  of  cane 

sugar  (the  molecular  weight  of  C12H22OU  =  342),  if  it  could  be  converted  into 

a  gas  at  0°  C.  and  760  mm.  Hg,  would  have  a  volume  of  22 -4 litres.     One  gramme 

of  sugar  therefore  at  the  same  temperature  and  pressure  would  have  a  volume  of 

22-4 

— —  litres  =  65-5  c.c.     In  Pfeffer's  experiment  the  gramme  of  sugar  was  dissolved 

342 

in  100  grammes  of  water,  making  a  total  volume  at  0°  C.  of  100-6  c.c.     The 

gaseous  pressure  of  the  sugar  molecules  in  this  solution  will  therefore  amount  to 

65-5 
— — —  =  0-651  atmosphere.     At    a    temperature  of  6-8  the  pressure  would  be 
100-6 

0-667  atmosphere,  as  against  the  observed  0-664  atmosphere. 

Pfeffer's  method  is  difficult  to  carry  out  and  is  not  applicable  to 
all  dissolved  substances,  since  the  cupric  ferrocyanide  membrane  is 
permeable  for  many  substances,  such  as  potassium  nitrate  or  hydro- 
chloric acid.  Other  indirect  methods  have  therefore  been  applied  to  the 
comparison  of  the  osmotic  pressures  of  different  solutions. 

DETERMINATION  OF  THE  OSMOTIC  PRESSURE  BY  PLASMO- 
LYSIS.  Solutions  which  have  the  same  osmotic  pressure  are  spoken 
of  as  isosmotic  or  isotonic.  The  method  of  plasmolysis,  which  we  owe 
to  the  botanist  De  Vries,  consists  essentially  in  the  comparison  of  the 
osmotic  pressure  of  solutions  with  that  of  the  cell  sap  of  certain  plant 
cells,  and  depends  on  the  fact  that  the  primordial  '  utricle,'  the  layer 
of  protoplasm  enclosing  the  cell  sap,  while  freely  permeable  to  water, 
is  impermeable  to  a  large  number  of  salts  and  other  crystalloids,  such 
as  sugar.  It  is  therefore,  so  far  as  concerns  these  substances,  '  semi- 
permeable.' The  cells  which  have  been  most  used  for  this  purpose 
are  the  cuticular  cells  on  the  mid-rib  of  the  lower  surface  of  the  leaves 
of  tradescantia  discolor.  If  some  of  these  cells  are  brought  into  a 
concentrated  salt  solution,  which  is  '  hypertonic  '  as  compared  with 
the  cell  sap,  water  passes  out  of  the  cell  into  the  salt  solution,  until 
the  contents  of  the  cell  attain  a  molecular  concentration  equal  to 
that  of  the  surrounding  medium.  The  protoplasmic  layer  therefore 
shrinks,  leaving  a  space  between  it  and  the  cell  wall  (Fig.  7,  p.  24).  If, 
the  outer  solution  has  a  smaller  molecular  concentration  than  the  cell 
sap,  water  passes  into  the  cell  and  causes  here  a  rise  of  pressure  which 
simply  presses  the  protoplasm  still  more  closely  against  the  cell  wall. 
If  we  determine  the  concentration  of  the  salt  solution  at  which  the 
shrinkage  of  the  protoplasm,  the  plasmolysis,  just  occurs,  and  another 
smaller  concentration  at  which  plasmolysis  is  absent,  we  know  that 
the  concentration  of  the  cell  sap  lies  between  those  of  the  two  salt 
solutions.  Thus,  if  plasmolysis  occurs  in  a  solution  containing  0'60  per 
cent,  sodium  chloride  and  is  absent  in  a  solution  containing  0'59  per 


THE  ENERGY  OF  MOLECULES  IN  SOLUTION 


141 


cent,  of  the  same  salt,  the  concentration  of  the  cell  sap  must  be  about 
equivalent  to  a  0595  per  cent.  NaCl  solution.  Solutions  of  different 
salts,  in  which  plasmolysis  just  occurs,  must  also  be  isotonic  with  one 
another.  Thus  a  TOl  per  cent,  solution  of  KNO3  is  found  to  be 
isotonic  with  a  0'58  per  cent.  NaCl  solution. 

DETERMINATION  BY  HAMBURGER'S  BLOOD-CORPUSCLE 
METHOD.  The  limiting  external  layer  of  red  blood  corpuscles  resembles 
the  primordial  utricle  of  plant  cells  in  being  impermeable  to  a  number 
of  dissolved  substances.  If,  therefore,  it  be  placed  in  a  solution  of 
smaller  concentration  than  the  corpuscle  contents,  it  will  swell  up  and, 
since  it  has  no  supporting  cell  wall,  the  increase  in  size  will  go  on  until 
the  corpuscle  bursts,  and  its  contained  red  colouring-matter,  hsemo- 
globin,  passes  into  solution  in  the  surrounding  fluid.  If  the  corpuscles 
be  then  allowed  to  settle  or  be  centrifuged,  the  fact  that  haemolysis 
has  occurred  is  shown  by  the  red  colour  of  the  clear  supernatant  fluid. 
With  a  given  sample  of  blood,  the  concentration  of  a  potassium  nitrate 
solution  is  found  at  which  the  first  traces  of  hsGmolysis  occur. 
In  order  to  determine  the  osmotic  pressure  of  a  solution,  say,  of 
sugar  or  of  sodium  chloride,  these  are  also  added  in  various  dilutions 
to  blood  corpuscles  until  we  get  solutions  in  which  hajmolysis  just 
occurs.  These  solutions  will  then  be  isotonic  with  the  first  determined 
potassium  nitrate  solutions.  As  an  example  of  this  method  may  be 
adduced  the  following  results  : 


Concentiatioii 

Concentration 

of  the  solution 

of  the  solution 

in  wliich  tlie 

in  which  the 

Mean 

blood  corpuscles 

blood  corpuscles 

concentration 

do  not  lose 

begin  to  lose 

luiiinoglobin 

bsemoglobiu 

Per  cent. 

Per  cent. 

Per  cent. 

Potassium  nitrate 

1-04 

0-9G 

1-00 

Sodium  chloride 

0-60 

0-56 

0-585 

Cane  sugar 

6-29 

5-63 

5-96 

Potassium  iodide 

1-71 

1-57 

1C4 

Sodium  iodide 

1-54 

1-47 

1-505 

Potassium  bromide 

1-22 

11 3 

1-17 

OSMOTIC  PRESSURE  OF  ELECTROLYTES.  It  will  be  noticed  in 
the  last  Table  that  the  isotonic  solutions  of  difterent  salts  contain  these 
salts  in  the  proportion  of  their  molecular  weights,  i.e.  each  solution 
contains  the  same  number  of  molecules  of  dissolved  salt.  For  the  term 
isotonic  we  might  therefore  employ  equimolecular.  When,  however, 
these  salts  are  compared  with  solutions  of  sugar,  it  is  foimd  that  the 
osmotic  pressures  of  the  salt  solutions  are  double  or  nearly  double 
those  of  equimolecular  solutions  of  sugar.       The    osmotic   pressure 


142  PHYSIOLOGY 

of  a  sugar  solution  is  equal  to  the  pressure  which  its  molecules 
would  exert  if  they  occupied  the  same  space  in  a  gaseous  form.  A 
dilute  salt  solution  therefore  acts  as  if  every  one  of  its  molecules 
were  doubled.  This  deviation  of  salt  solutions  from  solutions  of 
sugar  is  bound  up  with  the  power  of  the  former  to  conduct  an  electric 
current.  A  sugar  solution  conducts  electricity  little  better  than  pure 
water.  On  the  other  hand,  the  smallest  trace  of  salt  added  to  distilled 
water  enormously  increases  its  conducting  power.  As  Arrhenius  has 
shown,  this  increase  of  the  osmotic  pressure  of  a  salt  solution  is  deter- 
mined by  the  dissociation  which  all  these  salts  undergo  in  watery 

/         2    J    't    S      6      7      8  9 

(  —       I  I     ■    H     M       1  t--M- 


^/y//yyyy//y///////yy/////y//y////^^^^ 


y///A'y////////''.''y///^^i^//Ay/'^^^^^^^^^ 


Fig.  21.  Diagram  to  illustrate  Barger's  method  of  determi:img  osmotic 
pressure.  The  upper  figure  shows  the  capillary  tube  with  nme  alter- 
nate drops  of  cane  sugar  and  the  substance  under  investigation. 

solution.  A  dilute  solution  of  sodium  chloride  contains,  not  the  mole- 
cule NaCl,  but  an  equal  number  of  the  ions  Na  and  CI,  Na  carrying  a 
positive  charge  while  the  CI  ions  carry  a  negative  charge.  As  regards 
osmotic  pressure  and  various  other  properties,  each  of  these  charged 
ions  acts  as  a  whole  molecule.  It  is  the  existence  of  these  ions  which 
confers  on  the  salt  solution  the  power  of  conducting  electricity — a 
power  the  exercise  of  which  is  attended  with  a  dissociation  (an  electro- 
lysis) of  the  salt  into  its  constituent  ions,  the  electro-positive  ion 
being  d'eposited  at  the  negative  pole  while  the  electro-negative  ion 
is  deposited  at  the  positive  pole.  The  molecular  weight  of  NaCl  is 
58"5.  The  molecular  weight  of  glucose  is  180.  If  there  were  no  disso- 
ciation, a  0'58  per  cent,  solution  of  NaCl  would  be  isotonic  or  isosmotic 
with  a  1"8  per  cent,  solution  of  glucose.  On  account  of  the  ionic  disso- 
ciation or  ionisation,  it  is  actually  isosmotic  with  a  glucose  solution 
of  about  3-6  per  cent. 

INDIRECT  METHODS  OF  MEASURING  OSMOTIC  PRESSURE, 
Equimolecular  solutions  have  the  same  osmotic  pressures.  Since  the 
osmotic  pressure  of  a  solution  is  therefore  directly  dependent  on  the 


THE  ENERGY  OF  MOLECULES  IN  SOLUTION         143 

number  of  molecules  it  contains  in  unit  space,  any  method  which  will 
give  us  information  as  to  the  number  of  molecules  present  will  also 
enable  us  to  determine  the  osmotic  pressure.  Other  properties  of 
solutions  which,  like  the  osmotic  pressure,  are  functions  of  the  number 
of  molecules  present,  are  vapour-tension,  boiling-point,  freezing-point. 
The  presence  of  a  substance  in  solution  in  water  diminishes  its  vapour- 
tension  at  any  given  temperature,  raises  its  boiling-point,  and  depresses 
its  freezing-point,  and  the  extent  of  the  deviation  from  distilled  water 
is  proportional  to  the  number  of  dissolved  molecules  present.  The 
determination  of  the  rise  of  boiling-point,  though  much  employed  by 
chemists,  is  of  very  little  value  in  physiolog}',  owing  to  the  fact  that 
nearly  all  the  fluids  of  the  body  are  seriously  modified  in  character 
by  a  rise  of  temperature  to  100"  C.  On  the  other  hand,  Barger  has 
suggested  an  ingenious  method  in  which  the  alteration  of  vapour- 
tension  is  made  the  basis  of  a  method  for  determining  the  osmotic 
pressure  of  small  quantities  of  fluids  at  ordinary  temperatures.  And 
this  method  may  find  important  applications  in  physiolog}'. 

BARGER'S  METHOD,  Drops  of  the  fluid,  the  vapour-tension  of  which  it 
is  desired  to  ascertain,  are  drawn  up  into  a  tube  (To  mm.  in  diameter),  so  as  to 
alternate  with  small  drops  of  cane  sugar  solution  of  known  content  (Fig.  21). 
Water  in  a  state  of  vapour  wiU  pass  from  the  solution  of  which  the  vapour-tension 
is  the  higher.  By  observing  the  edge  of  a  drop  under  a  magnification  of  65 
diams.,  it  can  be  easily  seen  whether  it  has  grown  or  diminished  in  size.  If  the 
edge  of  the  drop  remains  stationary',  it  shows  that  the  vapour-tension  and  the 
osmotic  pressure  of  the  two  fluids  are  equal.  A  series  of  trials  is  made  viith 
different  strengths  of  salt  solution  until  this  equahty  is  estabUshed.  In  this 
method  only  minimal  quantities  of  material  are  required,  and  the  determination 
of  the  aqueous  tension  is  made  at  ordinary  temperatures. 

The  method,  however,  which  is  of  greatest  value  in  physiology 
is  the  measurement  of  the  depression  of  freezing-point.  The 
determination  is  carried  out  in  a  Beckmann's  apparatus  with  a 
thermometer  reading  to  -ruu°  C.  (Fig.  22).  A  solution  freezes  at 
a  lower  temperature  than  pure  water,  and  the  depression  of  freezing- 
point  is  proportional  to  the  number  of  molecules  present.  Thus  the 
freezing-point  of  a  1  per  cent,  solution  of  NaCl  is  — 061°  C.  The 
depression  of  freezing-point  is  generally  represented  by  the  Greek 
letter  A-  This  method  has  the  advantage  that  the  fluids  are  in 
most  cases  in  no  wise  altered  by  the  process  of  freezing,  and  it  can 
be  applied  to  solutions  containing  coagulable  proteins  which  would 
be  irretrievably  altered  by  any  considerable  rise  of  temperature. 
The  depression  of  freezing-point  can  be  converted  directly  into 
osmotic  pressure  by  multiplying  the  depression  of  freezmg-point 
observed  by  the  factor  122'7.  Thus  a  1  per  cent,  solution  of 
sodium  chloride  with  A  =  OGl  will  have  an  osmotic  pressure  of 
0-61  X  122-7  =  74-847  metres  of  water. 


144 


PHYSIOLOGY 


Every  substance  in  solution  possesses,  therefore,  a  certain  amount 
of  potential  energy  in  the  form  of  osmotic  pressure.  This  pressure  is 
independent  of  the  nature  of  the  substance  dissolved  and  is  deter- 
mined merely  by  its  molecular  concentration.  It  can  be  used  as  a 
driving  force  for  the  movement  by  diffusion  of 
the  molecules  themselves,  or  by  the  use  of 
appropriate  mechanisms  or  '  machines '  for  the 
performance  of  mechanical  work,  or,  as  will  be 
seen  later,  for  the  production  of  electrical 
differences  of  potential. 

In  addition  to  this  osmotic  or  volume 
energy  every  molecule  in  solution  can  be  re- 
garded as  endowed  with  a  chemical  energy, 
which  is  dependent  not  only  on  the  number  of 
molecules  present,  but  also  on  the  nature  of  the 
molecules.  In  the  case  of  electrolytes  and  of 
substances  which  are  susceptible  of  ionisation, 
the  potential  or  intensity  of  the  chemical  energy 
of  each  molecule  is  capable  of  measurement. 
On  the  other  hand,  the  chemical  energy  of  a 
substance  such  as  glucose  cannot  be  definitely 
expressed  apart  from  consideration  of  the  con- 
ditions under  which  it  is  present.  If  we  take 
the  whole  course  of  transformatioiis  undergone 
by  glucose  in  the  body,  we  may  speak  of  it  as 
having  a  potential  energy,  which  is  measured  by 
the  total  heat  energy  given  out  by  this  sub- 
stance on  its  complete  combustion  with  oxygen 
to  carbon  dioxide  and  water.  In  the  inter- 
mediate changes  which  it  undergoes  during  its 
metabolism  in  the  cells  of  the  body,  this  energy 
is  probably  set  free  by  degrees,  but  its  chemical 
energy  in  any  given  phase  cannot  be  measured 
unless  the  conditions  and  the  end  results  of 
the  chemical  changes  which  it  is  undergoing 
are  known.  This  chemical  energy  may 
be  utilised  for  the  production  of  heat, 
for  the  performance  of  chemical  work  in  the  building  up  of  other 
substances,  or,  by  the  multiplication  of  the  number  of  molecules  in  a 
solution,  for  the  production  of  increased  osmotic  pressure,  which  in 
its  turn  may  be  converted  into  the  energy  of  movement  either  of  masses 
or  of  molecules. 


Fig.  22.  B  e  ck  m  a  n  n '  s 
apparatus  for  determina- 
tion of  freezing-point. 


SECTION  II 

THE  PASSAGE   OF  WATER   AND   DISSOLVED 
SUBSTANCES   ACROSS  MEMBRANES 

We  have  already  seen  that  if,  in  a  solution,  the  concentration  of 
the  dissolved  substance  or  solute  is  not  uniform,  there  is  a  movement 
of  the  substance  from  the  place  of  higher  to  the  place  of  lower  concen- 
tration, and  this  movement  proceeds  until  the  concentration  is  equal 
throughout  the  fluid.  This  movement  of  dissolved  substances  through 
a  fluid  is  spoken  of  as  diffusion,  and  is  analogous  in  all  respects  with 
the  process  by  which  the  intermixture  of  gases  is  attained.  The  move- 
ment in  the  case  of  dissolved,  substances,  as  of  gases,  takes  place  from 
the  region  of  higher  to  the  region  of  lower  (osmotic)  pressure.  It  can 
therefore  be  ascribed  to  differences  of  pressure,  or  rather  to  the  factor 
which  we  regarded  as  responsible  for  the  production  of  the  pressure, 
viz.  the  movement  of  the  molecules  themselves.  The  rate  of  diffusion 
is  not  the  same  for  all  substances.  In  gases  the  rate  varies  inversely 
as  the  squaie  root  of  the  density  of  the  gas.  Thus  hydrogen  (density 
=  1)  diffuses  four  times  as  rapidly  as  oxygen  (density  =16).  We  find 
similar  differences  between  the  rates  of  diffusion  of  dissolved  substances 
— differences  which  also  are  determined  in  all  probability  by  the  weight 
and  size  of  the  individual  molecules,  although  the  relation  between 
molecular  weight  and  rate  of  diffusion  is  not  so  simple  as  the  ratio 
between  these  two  quantities  in  gases.  The  diffusibility  of  a 
substance  is  given  by  its  diffusion  coefl&cient.  The  amount  of  dissolved 
substance,  which  diffuses  in  a  unit  of  time  across  a  given  area  of  fluid, 
is  proportional  to  the  difference  between  the  osmotic  pressures  at 
two  cross-sections  of  the  column  of  fluid  at  an  infinitesimallv  small 
distance  apart.  If  we  take  a  cylindrical  mass  of  solution  which  is  one 
centimetre  long  and  has  a  sectional  area  of  one  square  centimetre 
(Fig.  23),  and  maintain  a  constant  difference  of  concentration  between 
A  and  B  =  1,  the  diffusion  coefficient  is  the  amount  of  substance  which 
diffuses  in  a  unit  of  time  from  A  to  B.  Thus  the  statement  that  the 
diffusion  coefficient  of  urea  is  OSlO  at  7-5"  C.  denotes  that  if  A 
be  continually  filled  with  a  1  per  cent,  solution  of  urea,  while  in  B  a 
constant  current  of  distilled  w^ater  is  kept  up  so  as  to  maintain  the 
concentration  at  zero,  in  the  course  of  a  day  0"810  gramme  of  urea 
will  pass  from  A  to  B  through  the  cylinder  of  one  centimetre  in  length 

145  10 


146 


PHYSIOLOGY 


and  one  square  centimetre  in  cross-section.  The  determination  of 
these  diffusion  coefficients  presents  many  difficulties.  The  task  is, 
however,  rendered  easier  by  the  fact,  first  ascertained  by  Graham, 
that  diffusion  of  salts  occurs  as  rapidly  through  a  solid  jelly  of  gelatin 
or  agar-agar  as  through  water.  It  is  therefore  possible  to  make  the 
plug  in  the  diagram  solid  by  the  admixture  of  one  of  these  two  sub- 
stances, and  to  maintain  a  constant  concentration  on  the  two  sides  of 
it  by  the  circulation  of  fluid  wdthout  affecting  the  rate  of  diffusion 
through  the  cylinder  by  setting  up  accidental  currents. 


More  important  from  the  physiological  point  of  view  than  diffusion 
through  fluids  is  the  exchange  of  fluids  (water  and  dissolved  substances), 
which  may  take  place  across  membranes.  Such  processes  are  of 
constant  occurrence  in  all  parts  of  the  body  and  are  concerned  in  such 
functions  as  the  formation  and  absorption  of  lymph,  the  absorption 
from  and  secretion  into  the  intestines,  absorption  from  serous  cavities, 
and  so  on.  In  many  of  these  functions  we  shall  have  to  consider  later 
whether  the  transference  across  the  membrane  is  determined  solely 
by  the  nature  and  concentration  of  the  fluids  on  the  two  sides  of  it  or 
is  effected  by  the  active  intervention,  involving  the  expenditure  of 
energy,  on  the  part  of  living  cells  forming  constituent  elements  of  the 
membrane  itself.  It  is  worth  our  while,  therefore,  to  consider  at  some 
greater  length  the  purely  physical  factors  which  may  be  concerned  in 
the  passage  of  water  and  dissolved  substances  across  membranes. 

In  the  case  of  fluids  containing  only  one  substance  in  solution,  the 
exchange  across  the  membrane  will  be  determined  entirely  by  the 
osmotic  pressures.  Thus,  if  two  watery  solutions,  with  the  same  osmotic 
pressure,  are  separated  by  a  membrane  through  which  diftusion  can 
take  place,  no  change  in  volume  occurs  on  either  side  of  the  membrane. 
If  the  solutions  on  either  side  of  the  membrane  are  of  unequal  osmotic 
pressure,  water  passes  from  the  side  where  the  pressure  is  lower  to 
the  side  where  it  is  higher,  and  there  is  a  simultaneous  passage  of  the 
solute  from  the  side  of  greater  to  the  side  of  less  concentration. 

If,  however,  the  solutions  on  the  two  sides  contain  dissimilar 
substances,  with  different  diffusion  coefficients,  the  conditions  are 
more  complicated,  and  may  tend  even  to  produce  a  movement  of 


PASSAGE  OF  WATER  AND  DISSOLVED  SUBSTANCES     H7 

fluid  in  apparent  opposition  to  the  difference  of  osmotic  pressure. 
Under  these  circumstances  the  nature  of  the  membrane  itself  is  all- 
important.  We  may  therefore  shortly  consider  the  various  modes  in 
which  interchanges  may  take  place  across  membranes  of  varying 
permeability.  We  shall  see  that  the  close  analogy  which  exists  between 
substances  in  solution  and  gases,  when  dealing  with  '  semi-permeable  ' 
membranes,  is  also  borne  out  by  experiment  when  used  to  predict 
the  behaviour  of  solutions  separated  by  such  permeable  membranes 
as  occur  in  the  body. 

The  simplest  case  is  that  in  which  two  fluids  are  separated  by  a 
perfect  semi-permeable  membrane  that  permits  the  passage  of  water 
but  is  absolutely  impermeable  to  dissolved  substances.  In  this  case 
the  transference  of  water  from  one  side  to  the  other  depends  entirely 
on  the  difference  of  osmotic  pressure  between  the  two  sides. 


A 

B 

Fig.  24. 

If  we  suppose  two  vessels,  A  and  B  (Fig.  24)  separated  by  such  a 
membrane,  A  containing  a  solution  of  a  and  B  a  solution  of  \],  water  will 
pass  from  A  to  B  so  long  as  the  osmotic  pressure  of  fi  is  greater  than  the 
osmotic  pressure  of  the  solution  of  a.  If  B  be  subjected  to  a  hydrostatic 
pressure  greater  than  the  osmotic  difference  between  the  two  fluids, 
water  will  pass  from  B  to  A  until  the  force  causing  filtration  or  transu- 
dation (the  hydrostatic  pressure)  is  equal  to  the  force  causing  absorp- 
tion into  B  (the  difference  of  osmotic  pressures).  Under  no  circum- 
stance will  there  be  any  transference  of  salt  or  dissolved  substance 
between  the  two  sides.  Such  semi-permeable  membranes  as  this, 
however,  rarely  occur  in  the  body  over  any  extent  of  surface.  The 
external  layer  of  the  cell  protoplasm  may  resemble  the  protoplasmic 
pellicle  of  plant  cells  in  possessing  this  '  semi- permeability '  ; 
but  in  nearly  all  cases  where  we  have  a  mc!ubrane  made  up  of  a 
number  of  cells,  it  can  be  shown  to  permit  the  free  passage  of  at 
any  rate  a  large  number  of  dissolved  substances. 

Let  us  now  consider  wiiat  will  occur  when  the  two  solutions  A  and 
B  are  separated  by  a  membrane  which  permits  the  free  passage  of 
salts  and  water.  If  the  osmotic  pressure  of  B  be  higher  than  A  at  the 
commencement  of  the  experiment,  the  force  tending  to  move  water 
from  A  to  B  will  be  equal  to  this  osmotic  difference.  But  there  is  at 
the  same  time  set  up  a  diffusion  of  the  dissolved  substances  from  B 


148  PHYSIOLOGY 

to  A  and  from  A  to  B.  The  result  of  this  diffusion  must  be  that  there 
is  no  longer  a  sudden  drop  of  osmotic  pressure  from  B  to  A,  and  the 
result  of  the  primary  osmotic  difference  on  the  movement  of  water 
will  be  minimised  in  proportion  to  the  freedom  of  diffusion  which 
takes  place  through  the  membrane.  Now  let  us  take  a  case  in  which 
A  and  B  represent  equimolecular  and  isotonic  solutions  of  a  and  /3. 
It  is  evident  that  the  movement  of  water  into  A  will  vary  as  k/p  —  Bp* 
=  0.  But  diffusion  also  occurs  of  a  into  B  and  of  /3  into  A.  Now  the 
amount  of  substance  diffusing  from  a  solution  is  proportional  to  the 
concentration,  and  therefore  to  its  osmotic  pressure,  as  well  as  to  its 
diffusion  coefficient. 

Hence  the  amount  of  a  diffusing  into  B  will  vary  as  A  f.ak 
(when  k  is  the  diffusion  coefficient). 

In  the  same  way  the  amount  of  /3  diffusing  into  A  will  vary  as 
Bp.  ^k'. 

Hence,  if  ak  is  greater  than  /3k',  i.e.  if  a  is  more  diffusible  than  ^, 
the  initial  result  must  be  that  a  greater  number  of  molecules  of  a 
will  pass  into  B  than  of  jS  into  A.  The  solutions  on  the  two  sides  of 
the  membrane  will  thus  be  no  longer  equimolecular,  but  the  total 
number  of  molecules  of  a  +  |8  in  B  will  be  greater  than  the  number 
of  molecules  of  a  +  /^  in  A,  and  this  difference  will  be  most  marked 
in  the  layers  of  fluid  nearest  the  membrane.  The  result,  therefore, 
of  the  unequal  diffusion  of  the  two  substances  is  to  upset  the  previous 
equality  of  osmotic  pressures.  The  layer  of  fluid  on  the  B  side  of  the 
membrane  will  have  an  osmotic  pressure  greater  than  the  layer  of 
fluid  in  immediate  contact  with  the  A  side  of  the  membrane,  and  there 
wall  thus  be  a  movement  of  water  from  A  to  B.  Hence  if  we  have 
two  equimolecular  and  isotonic  solutions  of  different  substances 
separated  by  a  membrane  permeable  to  the  solutes,  there  will  be 
an  initial  movement  of  fluid  towards  the  side  of  the  less  diffusible 
substance. 

We  have  an  exact  parallel  to  this  iii  Graham's  familiar  experiment, 
in  which  a  porous  pot  filled  with  hydrogen  is  connected  by  a  vertical 
tube  with  a  vessel  of  mercury.  In  consequence  of  the  more  rapid 
diffusion  outwards  of  the  hydrogen  than  of  atmospheric  air  inwards, 
the  pressure  within  the  pot  sinks  below  that  of  the  surrounding  atmo- 
sphere and  the  mercury  rises  several  inches  in  the  tube. 

We  must  therefore  conclude  that,  even  when  the  two  solutions  on 
either  side  of  the  membrane  are  isotonic,  there  may  be  a  movement  of 
fluid  from  one  side  to  the  other  with  a  performance  of  work  in  the 
process.  In  fact,  osmosis  may  occur  from  a  fluid  having  a  higher 
towards  a  fluid  having  a  lower  osmotic  pressure.  If,  for  example, 
equimolecular  solutions  of  sodium  chloride  and  glucose  be  separated 
*  Ap  =  osmotic  pressure  of  A,  &c. 


PASSAGE  OF  WATER  AND  DISSOLVED  SUBSTANCES    149 

by  a  peritoneal  membrane,  the  osmotic  flow  will  take  place  from 
the  fluid  havin<T  the  hifrher  osmotic  pressure — sodium  chloride.  * 
We  might  compare  with  this  experiment  the  results  of  separating 
hydrogen  at  one  atmosphere's  pressure  from  oxygen  at  two  atmo- 
spheres' pressure  by  means  of  a  plate  of  graphite.  In  this  case  the 
initial  result  will  be  a  still  further  increase  of  pressure  on  the  oxygen 
side  of  the  diaphragm — a  movement  of  gas  against  pressure  taking 
place  in  consequence  of  the  greater  diffusion  velocity  of  hydrogen. 

So  far  we  have  considered  only  the  behaviour  of  solutions  when 
separated  by  a  membrane,  the  permeability  of  which  to  salts  is  com- 
parable to  that  of  water  ;  so  that  the  passage  of  salts  through  the 
membrane  depends  merely  on  the  diffusion  rates  of  the  salts.  There 
can  be  no  doubt,  however,  that  we  might  get  analogous  movements 
of  fluid  against  total  osmotic  pressure  determined,  not  by  the  diffu- 
sibility  of  the  salts,  but  by  the  permeability  of  the  membrane  for  the 
salts — a  permeability  which  may  depend  on  a  state  of  solution  or 
attraction  existing  between  membrane  and  salts.  We  have  a  familiar 
analogue  to  such  a  condition  of  things  in  the  passage  of  gases  through 
an  india-rubber  sheet.  If  two  bottles,  one  containing  carbonic  acid, 
the  other  hydrogen,  be  separated  by  a  sheet  of  india-rubber,  carbon 
dioxide  passes  into  the  hydrogen  bottle  more  quickly  than  hydrogen 
can  pass  out  into  the  carbon  dioxide  bottle,  so  that  a  difference  of 
pressure  is  created,and  the  rubber  bulges  into  the  carbon  dioxide  bottle. 
We  might,  in  the  same  way,  conceive  of  a  membrane  which  permitted 
the  passage  of  dextrose  more  easily  than  that  of  urea.  The  importance 
of  the  membrane  in  determining  the  direction  of  the  osmotic  passage  of 
fluid  is  well  illustrated  by  Raoult's  experiments.  When  alcohol  and 
ether  were  separated  by  an  animal  membrane,  alcohol  passed  into 
the  ether,  whereas  if  vulcanite  were  employed  for  the  diaphragm,  the 
osmotic  flow  was  in  the  reverse  direction,  and  an  enormous  pressure 
was  set  up  on  the  alcohol  side  of  the  diaphragm."}* 

The  next  point  to  be  considered  is  the  passage  of  a  dissolved  sub- 
stance across  membranes,  in  consequence  of  differences  in  the  partial 
pressure  of  the  substance  in  question  on  the  two  sides  of  the  membrane. 
Stress  has  been  laid  by  Heidenhain  and  others  on  the  fact  that  in  the 

*  In  con.scquence  of  ionic  dis.sociation  of  the  sodium  chloride,  a  decinormal 
solution  of  this  salt  will  have  an  osmotic  pressure  nearly  twice  as  great  as  that 
of  a  similar  solution  of  the  non-ionised  glucose. 

t  Here  we  have  a  possible  clue  to  the  explanation  (A  some  phenomena  of 
cell  activity,  to  which  the  term  '  vital  '  is  often  a.ssigned.  In  the  swimming- 
bladder  of  fishes,  for  instance,  we  find  a  gas  which  is  extremely  rich  in  oxygen, 
and  the  oxygen  is  .said  to  have  been  secrctt^d  by  the  cells  lining  the  bladder. 
It  is,  however,  possible  that  the  processes  here  may  be  analogous  to  Graham's 
atmolysis,  and  that  the  bladder  may  represent  a  perfected  form  of  (iraham's 
india-rul)lxT  bag. 


150 


PHYSIOLOGY 


peritoneal  cavity,  as  well  as  from  the  intestine,  salt  may  be  taken  up 
from  fluids  containing  a  smaller  percentage  of  this  substance  than 
does  the  blood  plasma,  and  they  regard  this  absorption  as  pointing 
indubitably  to  an  active  intervention  of  living  cells  in  the  process. 
This  argument  requires  examination.  Let  us  suppose  the  two  vessels  A 
and  B  (Fig.  25)  to  be  separated  by  a  membrane  which  offers  free  passage 
to  water  and  a  difficult  passage  to  salts.  Let  A  contain  0-5  per  cent,  salt 
solution  and  B  a  solution  isotonic  with  a  1  per  cent.  NaCl,  but  con- 
taining only  0-65  per  cent,  of  this  salt,  the  rest  of  its  osmotic  tension 
being  due  to  other  dissolved  substances.  If  the  membrane  were 
absolutely  '  semi-permeable,'  water  would  pass  from  A  to  B  until 
the  two  fluids  were  isotonic,  i.e.  until  A  contained  1  per  cent.  NaCl 
(we  may  regard  volume  B  as  infinitely  great  to  simplify  the  argument). 


m 


B 


Fig.  25. 


If,  however,  the  membrane  permitted  passage  of  the  dissolved  sub- 
stances, the  course  of  events  might  be  as  follows  :  At  first  water  would 
pass  out  of  A,  and  salt  would  diffuse  in  until  the  percentage  of  NaCl 
in  A  was  equal  to  that  in  B.  There  would  now  be  an  equal  partial 
pressure  of  NaCl  on  the  two  sides  of  the  membrane,  but  the  total 
osmotic  i^ressure  of  B  would  still  be  higher  than  A.  Water  would 
therefore  still  continue  to  pass  from  A  to  B  more  rapidly  than  the  other 
ingredients  of  B  could  pass  into  A.  As  soon,  however,  as  more  water 
passed  out  from  A,  the  percentage  of  NaCl  in  A  would  be  raised  above 
that  in  B.  The  extent  to  which  this  occurs  will  depend  on  the  imper- 
meability of  the  membrane.  As  the  NaCl  in  A  reaches  a  certain 
concentration  it  will  pass  over  into  B,  and  this  will  go  on  until  equili- 
brium is  established  between  A  and  B.  Extending  this  argument  to 
the  conditions  obtaining  in  the  living  body,  we  may  conclude  that 
neither  the  raising  of  the  percentage  of  a  salt  in  any  fluid  above  that 
of  the  same  salt  in  the  plasma,  nor  the  passage  of  a  salt  from  a  hypo- 
tonic fluid  into  the  blood  plasma,  can  afford  in  itself  any  proof  of  an 
active  intervention  of  cells  in  the  process. 

In  the  case  of  the  pleura,  for  example,  we  seem  to  have  a  membrane  which 
is  very  imperfectly  semi -permeable.  It  is  permeable  to  salts,  but  presents 
rather  more  resistance  to  their  passage  than  to  the  pas.sage  of  water.  Hence 
on  injecting  0-5  per  cent.  NaCl  solution  into  the  pleural  cavity,  water  passes 


PASSAGE  OF  WATER  AND  DISSOLVED  SUBSTANCES    151 

from  the  pleural  fluid  into  the  blood,  until  the  percentage  of  sodium  chloride 
in  the  fluid  is  raised  perceptibly  above  that  in  the  blood  plasma.  The  limit 
of  the  resistance  of  the  pleural  membrane  to  the  passage  of  salt  is,  liowever,  soon 
reached,  and  then  salt  passes  from  pleural  fluid  into  blood  ;  but  in  every  case 
this  passage  is  from  a  region  of  higher  to  a  region  of  lower  partial  pressiure. 
Hence  at  a  certain  stage  of  the  experiment  we  And  a  higher  percentage  of  salt 
in  the  pleura  than  in  the  blood-vessels,  althougli  the  total  amount  of  salt  in 
the  plem-al  fluid  is  less  than  that  originally  put  in,  or,  in  other  words,  salt  has 
been  absorbed. 

We  have  already  seen  that  the  effective  osmotic  pressure  of  a 
substance,  i.e.  its  power  of  attracting  water  across  a  membrane, 
varies  inversely  as  its  clifEusibility,  or  as  the  permeability  of  the 
membrane  to  it.  What,  then,  will  be  the  efiect  if  on  one  side  of  the 
membrane  we  place  some  substance  in  solution  to  which  the  membrane 
is  impermeable  ? 

We  will  suppose  that  A  and  B  both  contain  1  per  cent.  NaCl,  but 
that  B  contains  in  addition  some  substance  x  to  which  the  membrane 
is  impermeable.  Since  the  osmotic  pressure  of  B  is  higher,  by  the 
partial  pressure  of  x,  than  that  of  A,  fluid  will  pass  from  A  to  B  by 
osmosis.  But  the  consequence  of  this  passage  of  water  will  be  to 
concentrate  the  NaCl  in  A,  so  that  the  partial  pressure  of  this  salt 
in  A  is  greater  than  in  B.  NaCl  will  therefore  diffuse  from  A  to  B, 
with  the  result  that  the  former  difference  of  total  osmotic  pressure 
will  be  re-established.  Hence  there  will  be  a  continual  passage  of 
both  water  and  salt  from  A  to  B,  until  B  has  absorbed  the  whole  of  A 
This  result  will  be  only  delayed  if  the  osmotic  pressure  of  A  is  at  first 
higher  than  B,  in  consequence  of  a  greater  concentration  of  NaCl  in  A. 
There  may  be  at  first  a  flow  of  fluid  from  B  to  A,  but  as  soon  as  the 
NaCl  concentration  on  the  two  sides  has  become  the  same  by  diflEusion, 
the  power  of  x  to  attract  water  from  the  other  side  will  make  itself 
felt,  and  this  attraction  will  be  proportional  to  the  osmotic  pressure 
of  X.  We  shall  have  occasion  to  discuss  a  specific  instance  of  this  case 
when  dealing  with  the  mechanism  of  absorption  of  fluid  by  the  blood- 
vessels from  the  connective  tissue  spaces. 

A  more  familiar  example  is  afforded  by  the  process  known  as 
dialysis.  Many  animal  membranes,  all  of  which  are  colloidal  in 
character,  and  others  such  as  vegetable  parchment,  while  freely 
permeable  to  salts,  are  impermeable  to  dissolved  colloids.  If,  therefore, 
a  fluid  containing  both  colloids  and  crystalloids  in  solution,  e.g. 
blood-serum,  be  enclosed  in  a  tube  of  vegetable  parchment,  which  is 
hung  up  in  a  large  bulk  of  distilled  water  (Fig.  20),  all  the  salts  dift'use 
out,  and  if  this  be  frequently  changed,  we  obtain  finally  a  fluid  within 
the  dialyser  free  from  salts  and  other  crystalloid  substances,  but 
containing  the  whole  of  the  colloidal  proteins  originally  present. 

Thus  the  transference  of  fluids  and  dissolved  substances  across 


152 


PHYSIOLOGY 


membranes  is  determined  not  only  by  the  osmotic  pressure  of  the 
solutions,  but  also  by  the  diffusion  coefficient  of  the  solutes  and  the 
permeabihty  of  the  membrane.  This  permeability  may  be  of  the 
same  character  as  the  permeability  of  water,  in  which  case  the  rates 
of  passage  of  the  dissolved  substances  across  the  membrane  vary  as 
their  diffusibilities,  and  are  therefore  probably  some  function  of  their 


Fig.  26.  Dialyser,  consisting  of  a  tube  of  parchment  paper  immersed 
in  a  vessel  through  which  a  constant  stream  of  sterile  distilled 
water  can  be  passed.     (Wrobleski.) 


molecular  weights.  On  the  other  hand,  the  membrane  may  exhibit 
a  certain  attraction  for,  or  power  of  dissolving,  some  of  the  solutes  to 
the  exclusion  of  others,  in  which  case  there  will  be  no  relation  between 
the  diffusibilities  and  the  rates  of  passage  of  the  dissolved  substances. 
In  a  recent  paper  Bayliss  has  drawn  attention  to  certain  other 
factors  which  may  determine  permanent  inequality  of  distribution  of 
a  salt  on  the  two  sides  of  a  membrane  permeable  to  the  salt.  If  Congo 
red,  which  is  a  compound  of  an  indiffusible  colloid  acid  with  sodium, 
be  placed  in  an  osmometer  which  is  immersed  in  water,  a  certain 
osmotic  pressure  is  developed.  On  adding  sodium  chloride  either  to 
the  inner  or  outer  fluid,  there  is  a  fall  in  the  osmotic  pressure  if  time 
be  allowed  for  equilibrium  to  be  established.     At  this  point  it  is  found 


PASSAGE  OF  WATER  AND  DISSOLVED  SUBSTANCES     153 

that  the  outer  fluid,  which  is  free  from  dye,  contains  a  larger  percentage 
of  sodium  chloride  than  the  inner  solution  of  dye.  This  diSerence  is 
permanent  and  is  more  marked  the  greater  the  concentration  of  the 
dye  salt.  In  the  following  Table  is  given  the  concentrations  of  the 
two  fluids  with  different  percentages  of  salt.      The  numbers  indicate 


Dye 

O.h.nw 

Iiisifie 

Out-i.i<.- 

30 

30 

30 

100 

52 
465 
<5500 
32-9 

30 
730 
180 
29-5 

the  litres  to  which  each  gramme  molecule  of  the  salt  is  diluted.  Appa- 
rently the  difierence  depends  on  the  fact  that  the  non-dissociated  salt 
must  be  equal  on  the  two  sides  of  the  membrane  and  that  the  dissocia- 
tion is  much  impeded  on  the  inner  side  on  account  of  the  presence 
there  of  another  salt  of  sodium.  A  sodium  salt  of  any  other  indiffusible 
substance,  e.g.  of  a  protein  such  as  caseinogen,  would  behave  in  a 
precisely  similar  fashion. 


SECTION  III 

THE   PROPERTIES   OF  COLLOIDS 

Although  the  chemical  changes  involved  in  the  varions  vital 
phenomena  occur  between  substances  in  watery  solution,  the  solution 
in  every  case  is  bound  up  within  the  meshes  or  adsorbed  by  the 
surfaces  of  a  heterogeneous  mass  of  colloids.  The  complex  chemical 
molecules  which  make  up  protoplasm  itself  are  all  colloidal  in  character. 
The  active  participation  of  colloids  in  chemical  reactions  introduces 
conditions  and  modes  of  reaction  differing  widely  from  those  which 
have  been  studied  in  watery  solutions.  Om-  knowledge  of  these  con- 
ditions is  still  very  imperfect,  but  the  important  part  played  by  col- 
loids in  the  processes  of  life  renders  it  necessary  to  discuss  in  some 
detail  their  properties  and  modes  of  interaction. 

The  term  colloid,  from  koW^,  glue,  was  first  introduced  by  Thomas 
Graham,  Professor  of  Chemistry  at  University  College  from  1836  to 
1855.  Graham  divided  all  substances  into  two  classes,  viz.  crystalloids, 
including  such  substances  as  salt,  sugar,  urea,  which  could  be  crystal- 
lised with  ease,  diffused  rapidly  through  water,  and  were  capable  of 
difiusing  through  animal  membranes ;  and  colloids,  which  included 
substances  such  as  gelatin  or  glue,  gum,  egg-albumin,  starch  and 
dextrin,  were  non-crystallisable,  formed  gummy  masses  when  their 
solutions  were  evaporated  to  dryness,  diffused  with  extreme  slowness 
through  water,  and  would  not  pass  through  animal  membranes.  The 
process  of  dialysis  was  therefore  introduced  by  Graham  for  the  sepa- 
ration of  crystalloids  from  colloids.  Although  the  broad  distinction 
drawn  by  Graham  between  colloids  and  crystalloids  still  holds  good, 
some  of  the  criteria  by  which  he  distinguished  the  two  classes  are  no 
longer  strictly  applicable.  For  instance,  it  has  been  shown  that  many 
typical  colloidal  substances,  such  as  haemoglobin,  can  be  obtained  in 
a  crystalline  form.  On  the  other  hand,  all  gradations  exist  between 
substances,  such  as  egg-albumin,  which  are  practically  indiffusible, 
and  those,  such  as  common  salt,  which  are  very  diffusible.  Graham 
pointed  out  that  colloids  exist  under  two  conditions  : 

(1)  In  a  state  of  solution  or  pseudo-solution,  in  which  they  form 
sols,  and  are  distinguished  as  hydrosols,  when  the  solvent  is  water ; 
and 

(2)  In  a  solid  state,  in  which  a  relatively  small  amount  of  the  colloid 

164 


THE  PROPERTIES  OF  COLLOIDS  155 

sets  with  a  large  amount  of  a  fluid,  such  as  water,  to  form  a  jelly. 
This  solid  form  is  known  as  a  gel.  The  most  familiar  instance  is  the 
jelly  which  is  obtained  on  dissolving  a  little  gelatin  in  hot  water  and 
allo\dng  the  mixture  to  cool.  Such  a  jelly  is  known  as  a  hydrogel. 
In  many  of  these  gels  the  water  can  be  replaced  by  other  fluids,  such 
as  alcohol,  without  any  alteration  in  the  appearance  of  the  solid, 
which  is  then  known  as  an  alcogel.  Another  example  of  an  alcogel 
is  the  jelly  which  can  be  made  by  dissolving  soap  in  warm  alcohol  and 
allowing  the  mixtiure  to  cool. 

A  number  of  these  colloidal  substances  can  be  shown  on  purely 
chemical  grounds  to  consist  of  monstrous  molecules.  Thus  the  mole- 
cular weight  of  haemoglobin  is  at  least  16,000,  and  one  must 
ascribe  similar  high  molecular  weights  to  such  substances  as  egg- 
albumin  and  globulin.  Still  greater  must  be  the  molecular  size  of  such 
substances  as  the  cell  proteins,  which  may  be  made  up  of  more  than 
one  type  of  protein  built  up  with  various  nucleins,  with  lecithin 
and  cholesterin,  to  form  a  gigantic  complex,  to  which  it  would  probably 
not  be  an  exaggeration  to  ascribe  a  molecular  weight  of  over 
100,000.  This  chemical  complexity  is  not,  however,  a  necessary 
condition  of  the  colloidal  state,  as  is  shown  by  the  existence  of 
colloidal  silica,  of  colloidal  ferric  hydrate  and  alumina,  and  even  of 
colloidal  metals.  On  neutralising  a  weak  solution  of  sodimu  silicate 
or  water-glass  by  means  of  HCl,  we  obtain  a  solution  which  contains 
sodium  chloride  and  silicic  acid.  On  dialysing  this  mixture  for  some 
days  against  distilled  water,  the  whole  of  the  NaCl  passes  out,  and  a 
solution  of  silicic  acid  or  colloidal  silica  is  left  in  the  dialyser.  This 
solution  can  be  concentrated  over  sulphuric  acid.  When  concentrated 
to  a  syrupy  consistence  it  becomes  extremely  unstable.  The  addition 
of  a  minute  trace  of  sodium  chloride  or  other  electrolyte  to  the  solution 
causes  it  to  set  at  once  to  a  solid  jelly  (gelatinous  silica),  the  change 
being  accompanied  by  an  appreciable  rise  of  temperatiu-e.  The  change 
is  irreversible,  in  that  it  is  not  possible  to  bring  the  silicic  acid  into 
solution  again  by  removal  of  the  electrolyte  by  means  of  dialysis. 
If,  however,  it  be  allowed  to  stand  with  weak  alkali  for  some  time,  it 
gradually  passes  into  solution.  Analogous  methods  are  employed  for 
the  preparation  of  colloidal  FcoOg  and  ALOg. 

Of  special  interest  are  the  colloidal  solutions  of  the  metals.  Faraday 
long  ago  pointed  out  that,  on  treating  a  weak  solution  of  gold  chloride 
with  phosphorus,  it  underwent  reduction  with  the  formation  of  metallic 
gold.  The  gold,  however,  was  not  precipitated,  but  remained  in  sus- 
pension or  pseudo-solution,  giving  a  deep  red  *  or  a  blue  liquid,  accord- 
ing to  the  conditions  under  which  the  reaction  was  effected.     This 

*  Ruby  glass  is  a  colloidal  '  solid '  solution  of  gold  in  a  mixture  of 
silicates. 


15G  PHYSIOLOGY 

solution  was  homogeneous  in  that  it  could  be  filtered  without  change, 
and  could  be  kept  for  months  without  deposition  of  the  gold.  The 
latter  was,  however,  thrown  down  on  addition  of  mere  traces  of 
impurity,  though  greater  stability  could  be  conferred  on  the  solution 
by  adding  to  it  a  little  '  jelly,"  i.e.  a  weak  solution  of  gelatin.  In 
1899  Bredig  showed  how  similar  hydrosols  might  be  prepared  from  a 
number  of  different  metals,  viz.  by  the  passage  of  a  small  arc  or 
electric  sparks  between  metallic  terminals  submerged  in  distilled  water. 
If,  for  example,  the  terminals  be  of  platinum,  the  passage  of  the  current 
is  seen  to  be  accompanied  by  the  giving  off  of  brown  clouds,  which 
spread  into  the  surrounding  fluid.  These  clouds  consist  of  particles 
of  platinum  of  all  sizes.  The  larger  settle  at  the  bottom  of  the  vessel, 
the  smaller — which  are  ultra-microscopic  in  size,  *'.e.from  5  ^/i  to  40  /x/jt* 
— ^remain  in  suspension,  and  we  obtain  a  brown  fluid  which  can  be 
filtered  through  paper  or  even  through  a  Berkefeld  filter  without 
losing  its  colour.  It  may  be  kept  for  months  without  any  deposit 
taking  place.  The  addition  of  minute  traces  of  electrolytes  precipitates 
the  platinum  particles,  leaving  a  colourless  fluid.  We  shall  have  to 
return  later  on  to  the  consideration  of  the  behaviour  of  these  metallic 
sols. 

PROPERTIES  OF  GELS.  A  typical  hydrogel  is  the  firm  mass  in 
which  a  solution  of  gelatin  sets  on  cooling.  It  is  clear,  hyaline,  appa- 
rently structureless,  and  possesses  considerable  elasticity,  i.e.  resist- 
ance to  deforming  force.  It  ma}^  be  regarded  as  formed  by  the  separation 
of  the  warm  pseudo-solution  of  gelatin  into  two  phases  :  first  a  solid 
phase,  rich  in  gelatin  and  forming  a  tissue  or  meshwork,  in  the  inter- 
stices of  which  is  embedded  the  second  phase,  consisting  of  a  very 
weak  solution  of  gelatin.  If  the  process  be  observed  under  the  micro- 
scope, according  to  Hardy,  minute  drops  first  appear,  which,  as  they 
enlarge,  touch  one  another  and  form  networks.  In  stronger  solutions 
the  first  structures  to  make  their  appearance  consist,  not  of  the  more 
concentrated  phase,  but  of  droplets  of  the  dilute  solution  of  gelatin  ; 
the  stronger  solution  collects  round  these  drops  and  solidifies  to  a 
honeycomb  structure.  In  many  cases  the  more  fluid  part  of  the 
gel  is  practically  pure  water.  In  such  a  case  immersion  in  alcohol 
causes  a  diffusion  outwards  of  the  water,  which  is  replaced  by  alcohol 
with  the  formation  of  an  alco-gel.  In  a  dry  atmosphere  the  gel 
loses  water  and  becomes  shrivelled  and  dry,  but  in  some  cases,^e.gf. 
gelatin,  it  can  resume  its  former  size  and  characters  on  immersion 
in  water.  Other  gels,  such  as  silicic  acid  or  ferric  hydrate,  lose  the 
power  of  swelling  up  after  drying.  The  change  in  them  is  therefore 
irreversible.    A  gel  adheres  to  the  last  traces  of  water  with  extreme 

*  One  /i  is  one-thousandth  of  a  niillimetrc  ;  one  /u/<  is  one-thousandth  fi,  i.e, 
one-millionth  of  a  millimetre.   . 


THE  PROPERTIES  OF  COLLOIDS  157 

tenacity.  In  consequence  of  its  structure,  it  presents  an  enormous 
extent  of  surface  on  which  adsorption  can  take  place.  At  this  surface 
the  vapour-tension  of  fluids  is  diminished,  as  well  as  the  osmotic 
pressure  of  dissolved  substances.  On  this  account  gelatin  must  be 
heated  for  many  hours  at  a  temperature  of  120°  C.  in  order  to  be 
thoroughly  dried.  When  dry,  it,  as  well  as  other  solid  colloids,  can 
exert  a  considerable  amount  of  energy  when  caused  to  swell  up  by 
moistening.  This  energy  was  made  use  of  by  the  ancient  Egyptians 
in  the  quarrying  of  their  stone  blocks  by  the  insertion  of  wedges  of 
wood  ;  water  was  poured  on  the  wood,  and  the  swelling  of  the  wedges 
split  the  rock  in  the  desired  direction.* 

It  is  on  account  of  the  extent  of  surface  that  it  is  practically  impos- 
sible to  wash  out  the  inorganic  constituents  from  a  gel.  The  diminu- 
tion of  the  osmotic  pressure  of  many  dissolved  substances  at  surfaces 
causes  the  concentration  at  the  surface  of  a  gel  to  be  greater  than  that  in 
the  surrounding  medium.  Thus,  if  dry  gelatin  be  immersed  in  a  salt 
solution  it  will  swell  up,  but  the  solution  which  it  absorbs  will  be  more 
concentrated  than  the  solution  in  which  it  is  immersed,  so  that  the 
proportion  of  salt  in  the  latter  will  be  diminished.  When,  however, 
equilibrium  is  established  between  a  gel  and  the  surrounding  fluid, 
it  is  found  to  present  no  appreciable  resistance  to  the  passage  of 
dissolved  crystalloids.  Thus  salt  or  sugar  diffuses  through  a  column  of 
solid  gelatin  as  if  the  latter  were  pure  water.  On  the  other  hand, 
gels  are  practically  impermeable  to  other  colloids  in  solution.  This 
impermeabiUty  is  made  use  of  in  the  separation  of  crystalloids  from 
colloids  by  dialysis,  membranes  used  in  this  process  being  generally 
irreversible  and  heterogeneous  gels  [i.e.  vegetable  parchment,  animal 
membranes).  Other  gels,  such  as  tannate  of  gelatin  or  copper  ferro- 
cyanide,  are  not  only  impermeable  to  colloids,  but  also  to  many 
crystalloid  substances.  These  membranes,  therefore,  were  used  by 
Pfeffer  for  the  determination  of  the  osmotic  pressure  of  such  crystal- 
loids as  cane  sugar. 

PROPERTIES  OF  HYDROSOLS.  Substances  such  as  dextrin  or 
egg-alhiiiiiiii  may  be  dissolved  in  water  in  almost  any  concentration. 
If  a  solution  of  egg-albumin  be  concentrated  at  a  low  temperature, 
it  becomes  more  and  more  viscous  and  finally  solid.  But  there  is  no 
distinct  point  at  which  the  fluid  passes  into  the  solid  condition.  Such 
solutions  are  known  as  hydrosols.  Much  discussion  has  arisen  whether 
they  are  to  be  regarded  as  true  solutions  or  as  pseudo-solutions  or 
suspensions.  The  chief  criterion  of  a  true  solution  is  its  homogeneity. 
In  a  solution  the  molecules  of  the  solute  are  equally  diffused  throughout 
the  molecules  of  the  solvent,  and  it  is  impossible,  without  the  applica- 

*  According  to  Rodewald,  the  maximal  pressure  with  which  dry  starch 
attracts  water  amounts  to  2073  kilo,  per  sq.  cm. 


158  PHYSIOLOGY 

tion  of  energy,  to  separate  one  from  the  other.  Thus  filtration,  gravita- 
tion leave  the  composition  of  the  solution  unchanged.  It  is  true  that, 
by  the  employment  of  certain  kinds  of  membrane,  e.g.  the  semi-per- 
meable copper  ferrocyanide  membrane,  it  is  possible  to  separate 
solute  from  solvent,  but  in  this  case  the  force  required  to  effect  the 
filtration  is  enormous  and  grows  with  every  increase  in  the  strength 
of  the  solution.  The  measure  of  the  force  required  is  the  osmotic 
pressure  of  the  solution,  and  it  becomes  natural  therefore  to  regard 
the  possession  of  an  osmotic  pressure  as  a  distinguishing  criterion  of 
a  true  solution.  Is  there  any  evidence  that  colloid  solutions  also 
display  an  osmotic  pressure  ? 

Sabanejeff  has  attempted  to  decide  this  question  in  an  indirect  manner, 
i.e.  by  the  determination  of  the  depression  of  freezing-point  caused  by  the 
addition  to  water  of  various  colloids.  The  depressions  observed  by  this  author 
were  so  small  that  they  might  be  regarded  as  falling  within  the  limits  of  experi- 
mental error.  Assuming  that  the  depression  in  each  case  was  due  to  the  presence 
of  the  dissolved  colloid,  Sabanejeff  arrived  at  the  following  molecular  weights 
for  certain  colloids : 


Tamain 

1,322 

Egg-album'n  . 

15,000 

Starch  . 

.    over 

30,000 

Silicic  acid 

jj 

49,000 

I  have  shown,  however,  that  it  is  possible  to  determine  the  osmotic  pressure 
of  colloidal  solutions  directly,  taking  advantage  of  the  fact  that  colloidal 
membranes,  while  permitting  the  passage  of  water  and  salts,  are  impermeable 
to  colloids  in  solution. 

The  method  originally  adopted  Avas  as  follows  :  In  order  to  determine  the 
osmotic  pressure  of  the  colloidal  constituents  of  blood-serum,  150  c.c.  of  clear 
filtered  serum  are  filtered  under  a  pressure  of  30-40  atmospheres  tlirough  a 
porous  cell  which  has  been  previously  soaked  with  gelatin.  The  first  10-20  c.c. 
of  filtrate,  which  contain  the  water  squeezed  out  of  the  meshes  of  the  gelatin 
and  have  also  lost  salt  in  consequence  of  absorption  by  the  gelatin,  are  rejected. 
The  filtration  is  allowed  to  go  on  for  another  twenty-four  hours,  when  about 
75  c.c.  of  a  clear  coloiirless  filtrate  is  obtained,  perfectly  free  from  all  traces 
of  protein,  but  possessing  practically  the  same  freezing-point  as  the  original 
serum.  (Although  the  colloids,  if  they  possess  an  osmotic  pressure,  must  also 
ca  ise  a  depression  of  the  freezing-point,  any  such  depression  would  be  within 
the  errors  of  observation,  since  a  pressure  of  45  mm.  Hg.  would  correspond 
only  to  0'005  C.)  The  concentrated  serum  left  behind  in  the  filter  is  then  put 
into  the  osmometer,  the  filtrate  being  used  as  tlic  inner  fluid.  The  construction 
of  the  osmometer  is  shown  in  the  diagram  (Fig.  57). 

The  tube  BB  is  made  of  silver  gauze,  connected  at  each  end  to  a  tube  of 
solid  silver.  Romid  the  gauze  is  WTappcd  a  piece  of  peritoneal  membrane, 
as  in  making  a  cigarette.  This  is  painted  all  over  with  a  solution  of  gelatin 
(10  per  cent.)  and  then  a  second  layer  of  membrane  applied.  Fine  thread  is  now 
twisted  many  times  round  the  tube  to  prevent  any  disturbance  of  the  membranes, 
and  the  whole  tube  is  soaked  for  half  an  hour  in  a  warm  solution  of  gelatin. 
In  this  way  one  obtains  an  even  layer  of  gelatin  between  two  layers  of  peri- 
toneal membrane  and  supported  by  the  wire  gauze.  The  tube  so  prepared  is 
placed  within  a  wide  tube,  AA,  which  is  provided  with  two  tubules  at  the  top. 


THE  PROPERTIES  OF  COLLOIDS 


159 


One  of  these,  0,  is  for  filling  the  outer  tube  ;  the  other  is  fitted  with  a  mercurial 
manometer,  M.  Two  small  reservoirs,  CC,  are  connected  with  the  outer  ends 
of  BB,  by  means  of  rubber  tubes.  The  whole  apparatus  is  placed  in  a  wooden 
cradle,  DD,  pivoted  at  X,  and  provided  with  a  cover  so  that  it  may  be  filled 
with  fluids  at  different  temperatures  if  necessary.  The  colloid  solution  is  placed 
in  AA,  and  the  reservoirs,  CC,  and  inner  tube,  BB,  are  filled  with  the  filtrate,  i.e. 
with  a  salt  solution  approximately  or  absolutely  isotonic  with  the  colloid  solution. 
The  apparatus  is  then  made  to  rock  continuously  for  days  or  weeks  by  means  of 
a  motor.  In  this  way  the  fluid  on  the  two  sides  of  the  membrane  is  continually 
removed,  and  the  attainment  of  an  osmotic  equilibrium  facihtated.  With  this 
apparatus  I  found  that  the  colloids  in  blood-serum,  containing  from  7  to  8  per 
cent,  proteins,  had  an  osmotic  pressure  of  25  to  30  mm.  Hg.,  which  would  corre- 
spond to  a  molecular  weight  of  about  30,000. 

A  more  convenient  form  of  osmometer  lias  been  devised  by  B. 
Moore,  using  parchment  paper  as  the  membrane.     With  this  osmo- 


D 


meter,  the  existence  of  an  osmotic  pressure  in  colloidal  solutions 
has  been  definitely  established  both  by  Moore  in  the  case  of  haemo- 
globin, proteins,  and  soaps,  and  by  Bayliss  in  the  case  of  colloidal 
dyes,  such  as  Congo  red.  The  osmotic  pressure  of  haemoglobin  was 
found  by  Hufner  to  correspond  to  a  molecular  weight  of  about 
16,000,  i.e.  a  molecular  weight  already  deduced  from  its  composition 
and  its  combining  powers  with  oxygen.  Often,  however,  the  osmotic 
pressure  shows  a  molecular  weight  which  is  very  nnich  smaller  than 
would  be  expected  from  the  molecular  weight  of  the  substance,  owing 
to  the  fact  that  colloids  in  solution  may  be  in  many  different  condi- 
tions of  aggregation.  Thus  the  molecule  of  colloidal  silica  must  be 
many,  probably  thousands  of,  times  larger  than  the  molecule  as 
represented  by  HgSiOa.  The  osmotic  pressure  being  proportional 
to  the  number  of  molecules  in  a  given  volume  of  solution,  the  larger 
the  aggregate  the  smaller  would  be  the  total  number  of  molecules, 
and  the  smaller  therefore  the  osmotic  pressure  of  the  solution. 

It  is  in  consequence  of  the  huge  size  of  the  molecular  aggregates 


160  PHYSIOLOGY 

that  colloidal  solutions,  such  as  starch  or  glycogen,  and  probably 
globulin,  display  no  appreciable  osmotic  pressure.  We  cannot 
divide  colloidal  solutions  into  two  classes,  viz.  those  which  form 
true  solutions  and  present  a  feeble  osmotic  pressure,  and  those  which 
only  form  suspensions  and  therefore  exert  no  osmotic  pressure.  In 
inorganic  colloids,  such  as  arsenious  sulphide,  Picton  and  Linder 
have  shown  that  all  grades  exist  between  true  solutions  and 
suspensions.  With  increasing  aggregation  of  the  molecules,  the 
suspension  becomes  coarser  and  coarser  until  finally  the  sulphide 
separates  in  the  form  of  a  precipitate. 

The  measurement  of  the  osmotic  pressure  of  the  colloids  of  serum 
points  to  their  having  a  molecular  weight  of  about  30,000.  Chemical 
evidence  shows  that  haemoglobin  has  a  molecular  weight  of  about 
16,000,  and  we  have  every  reason  to  believe  that  the  much  more 
complex  molecules  forming  the  cell  proteins  may  have  molecular 
weights  of  many  times  this  amount.  When,  however,  we  arrive 
at  molecular  weights  of  these  dimensions,  the  disproportion  between 
the  size  of  the  molecules  and  those  of  the  solvent,  water,  becomes 
so  great  that  a  homogeneous  distribution  of  the  two  substances, 
solute  and  solvent,  is  no  longer  possible.  The  size  of  a  molecule  of 
water  has  been  reckoned  to  be  -7  X  10  —  8  mm.  A  molecule  10,000 
times  as  large  would  have  a  diameter  of  -7  X  10  —  4  mm.  =  -07  /x,  a 
size  just  within  the  limits  of  microscopic  vision.  Long  before  molecules 
attained  such  a  size  they  would  no  longer  react  according  to  the  laws 
which  have  been  derived  from  the  study  of  the  behaviour  of  the  almost 
perfect  gases,  but  would  possess  the  properties  of  matter  in  mass. 
They  have  a  surface  of  measurable  extent,  and  their  relations  to  the 
molecules  of  water  or  solvent  will  be  determined  by  the  laws  of 
adsorption  at  surfaces  rather  than  by  the  laws  of  interaction  of  mole- 
cules. As  a  matter  of  fact  we  find  that  such  solutions  present  an 
amazing  mixture  of  properties,  some  of  which  betray  them  as  mechani- 
cal suspensions,  while  others  partake  of  the  nature  of  the  chemical 
reactions  such  as  those  studied  in  the  simpler  compounds  usually 
dealt  with  by  the  chemist. 

OPTICAL  BEHAVIOUR  OF  HYDROSOLS.  Nearly  all  colloidal 
solutions  present  what  is  known  as  the  Faraday-Tyndall  phenomenon. 
When  a  beam  of  light  is  passed  through  an  optically  homogeneous 
fluid,  the  course  of  the  beam  is  invisible.  A  beam  of  sunlight  falling 
into  a  dark  room  is  rendered  visible  by  impinging  on  and  illuminating 
the  dust  particles  in  its  course.  Each  of  these  particles,  being  illu- 
minated, acts  as  a  centre  of  dispersion  of  the  light,  so  that  the  course  of 
the  beam  is  apparent  to  a  person  standing  on  one  side  of  it.  Tyndall 
showed  that,  if  the  particles  were  sufficiently  minute,  the  light  dis- 
persed by  them  at  right  angles  to  the  beam  was  polarised.     This 


THE  PROPERTIES  OF  COLLOIDS  161 

can  be  easily  tested  by  looking  at  the  beam  through  a  Nicol's  prism. 
If  the  prism  be  slowly  rotated,  it  will  be  found  that,  while  at  one  posi- 
tion the  light  is  bright,  in  the  position  at  right  angles  to  this  it  becomes 
dim  or  is  extinguished.  The  production  of  the  Tyndall  phenomenon 
may  therefore  be  regarded  as  a  test  for  the  presence  of  ultra-microscopic 
particles,  varying  in  size  from  5  to  50  fi/n.  The  phenomenon  is 
perhaps  too  sensitive  to  be  taken  as  a  proof  that  a  fluid  presenting 
it  is  a  suspension  rather  than  a  solution.  It  is  shown,  for  instance,  by 
solutions  of  many  bodies  of  high  molecular  weight,  such  as  raffinose 
(a  tri-saccharide)  or  the  alkaloid  brucine  (Bayliss). 

A  particle  having  a  diameter  less  than  half  the  wave-length  of 
light,  i.e.  about  300  \  or  -3  /x,  cannot  be  clearly  distinguished  under  any 
power  of  the  microscope.  The  fact  that  an  ultra-microscopic  particle 
may  serve  as  a  centre  for  disp3rsal  of  light  may  be  used  for  rendering 
such  particles  visible  under  the  microscope.  For  this  purpose  a  strong 
beam  of  light  is  passed  in  the  plane  of  the  stage  of  the  microscope 
through  a  cell  containing  the  hydrosol,  which  is  then  examined  under 
a  high  power.  The  arrangement  for  this  purpose  was  first  devised 
by  Zsigmondy  and  Siedentopf .  On  examining  with  this  apparatus  a 
dilute  gold  sol,  we  see  a  swarm  of  dancing  points  of  light,  "  like  gnats 
in  the  sunhght,"  which  move  rapidly  in  all  directions,  rendering  it 
almost  impossible  to  count  their  number  in  the  field.  The  coarser 
particles  present  shght  oscillations  similar  to  those  long  known  as 
the  Brownian  movements.  The  smallest  particles  which  can  be 
seen  show  a  combined  movement,  consisting  of  a  translatory  move- 
ment, in  which  the  particle  passes  rapidly  across  the  field  in  one- 
sixth  to  one-eighth  of  a  second,  and  a  movement  of  oscillation  of 
much  shorter  period.  The  representation  of  the  course  of  such  a 
particle  is  given  in  Fig.  28. 

The  size  of  the  smallest  particles  seen  in  this  way  may  amount  to 
•1)05^.  Not  all  colloidal  solutions  show  these  particles  in  the  ultra- 
microscope.  In  some  cases  this  is  due  simply  to  the  small  size  of  the 
particles,  and  the  addition  of  any  substance,  which  causes  aggregation 
and  therefore  increase  in  the  size  of  the  particles,  will  bring  them  into 
view.  In  others  the  absence  of  optical  inhomogeneity  may  be  due 
to  the  coincidence  of  the  refractive  indices  of  the  two  phases  of  the 
hydrosol,  or  to  the  absence  of  any  surface  tension  and  therefore  dividing 
surfaces  between  the  two  phases. 

ELECTRICAL  PROPERTIES  OF  COLLOIDS 

In  the  case  of  many  hydrosols  tlie    ultra-microscopic  particles 

of  which  they  are  composed  carry  an  electric  charge  which,  according 

to  the  nature  of  the  solution,  may  be  either  positive  or    negative. 

On  this  account,  the  particles  move  if  placed  in  an  electric  field,   and 

11 


162 


PHYSIOLOGY 


the  direction  of  their  movement  reveals  the  nature  of  their  change. 
Thus  colloidal  ferric  hydrate  is  electro- positive  and  travels  from  anode 
to  cathode.  Silicic  acid,  in  the  presence  of  a  trace  of  alkali,  is  electro- 
negative, and  the  same  is  true  of  a  hydrosol  of  gold.  When  a  current  is 
passed  through  these  hydrosols,  the  colloidal  particles  travel  to  the 
anode,  where  they  are  precipitated.  In  certain  colloids  the  charge 
varies  according  to  the  conditions  under  which  they  are  brought 
into  solution.  If,  for  instance,  egg-white  be  diluted  ten  times 
with  distilled  water,  filtered  and  boiled,  no  precipitate  occurs,  but 
we  obtain  a  colloidal  suspension   of  albumin.      When  thoroughly 


Fig.   28.     Movements  of  two  particles  of  india-rubber  latex  in  colloidal  solution, 
recorded  by  cinematograph  and  idtra-microscope.     (Henri.) 


dialysed,  this  protein  is  insoluble  in  pure  water,  but  is  soluble  in  traces 
of  either  acid  or  alkali.  In  acid  solution  the  protein  particles  carry 
a  positive  charge,  whereas  in  alkaline  solution  their  charge  is  negative. 
The  charged  condition  of  these  particles  must  play  a  considerable 
part  in  keeping  them  asunder  and  therefore  in  preventing  their  aggrega- 
tion and  precipitation.  This  is  shown  by  the  fact  that  any  agency 
which  will  tend  to  discharge  them  will  cause  precipitation  and  coagu- 
lation. Among  such  agencies  is  the  passage  of  a  constant  current, 
just  mentioned.  To  the  same  action  is  due  the  coagulative  or  pre- 
cipitating effects  of  neutral  salts.  Thus  any  of  the  colloids  we  have 
mentioned,  ferric  hydrate,  silica,  gold,  or  boiled  albumen,  are  thrown 
down  by  the  addition  of  traces  of  neutral  salts,  and  it  is  found  that 
in  this  process  they  carry  with  them  some  of  the  ion  with  the  opposite 
charge  to  that  of  the  colloidal  particle.  Thus,  in  the  precipita- 
tion of  the  electro-positive  ferric  hydrate  the  acid  ion  of  the  salt 
i^  the  determining  factor,  the  coagulative  power  increasing  rapidly 


THE  PROPERTIES  OF  COLLOIDS  163 

with  the  valency  of  the  acid.  On  the  other  hand,  in  the  precipitation 
of  a  gold  sol  the  electro-positive  ion  is  the  effective  agent,  and  here 
again  the  coagulative  effect  is  enormously  increased  by  a  rise  in 
valency.  This  is  shown  in  the  following  Tables,  where  it  will  be  seen 
that,  in  the  coagulation  of  gold,  barium  chloride,with  the  divalent  Ba'', 
is  seven  times  as  powerful  as  K2SO4,  containing  the  univalent  K'. 
On  the  other  hand,  in  the  precipitation  of  the  electro-positive  ferric 
hydrate,  K2SO4,  with  a  divalent  S0/\  is  400  times  as  effective  as 
BaCL. 

Amount  of  Salt  necessary  to  pre'jipitate  Colloidal 
Solutions 


To  coagulate  FeoO;j 
K2SO4   1  g.  mol.  in  4,000,000  c.c. 
MgS04     „       „     „    4,000,000    „ 
BaCl2       „       „     „         10,000    „ 
NaCl        „       „     „         30,000   „ 


To  coagulate  Gold 
BaClg   1  g.  mol.  in  500,000  c.c. 
NaCl       „       „     „     72,000   „ 
K0SO4    „       „     „     75,000   „ 


The  presence  of  a  charge  is  not,  however,  a  necessary  condition 
for  the  stability  of  a  colloidal  solution.  Thus  the  proteins  of  serum, 
globulin  in  a  weak  saline  solution,  or  gelatin,  present  no  drift  when 
exposed  to  a  strong  electric  field.  In  such  cases  one  must  assume 
the  stability  of  the  solution  to  be  determined  by  the  absence  of  any 
surface  tension  between  the  two  phases  in  the  solution,  or  between  the 
particles  of  solute  and  the  solvent.  Thus  no  force  is  present  tending 
to  cause  aggregation  of  the  particles. 

The  charged  condition  of  a  colloidal  particle  makes  it  behave  in  an 
electric  field  in  much  the  same  way  as  a  charged  ion  of  an  electrolyte, 
and  this  similarity  extends  also  to  its  chemical  behaviour,  so  that 
wc  have  a  class  of  compounds  formed  resembling  in  many  respects 
chemical  combinations,  but  differing  from  these  in  the  absence 
of  definite  quantitative  relations  between  the  reacting  substances. 
This  class  of  continuously  varying  chemical  compounds  has  been 
designated  by  Van  Bemmelen  absorption  compounds.  Since,  how- 
ever, the  interaction  must  take  place  at  the  surface  layer  bounding 
the  charged  particles,  it  will  be  perhaps  better,  as  Bayliss  has  done, 
to  use  the  term  adsorption.  The  huge  molecules  or  aggregates  of 
molecules  which  distinguish  the  colloidal  state  form  a  system  with 
a  considerable  inertia,  so  that  we  have  a  tendency  to  the  establish- 
ment of  conditions  of  false  equilibrium.  Once  a  configuration  is 
established,  it  is  necessary,  in  consequence  of  the  inertia,  to  overstep 
widely  the  conditions  of  its  formation  in  order  to  destroy  it.  Thus 
a  10  per  cent,  gelatin  solution  sets  at  21°  C,  but  does  not  melt  until 
warmed  to  29-6°  C.  Solutions  of  agar  in  water  set  at  about  35^  C,  but 
do  not  melt  under  90°  C.  A  gel  of  jiclatin  takes  twentv-four  hours 
after  setting  to  attain  a  constant  melting-point. 


164 


PHYSIOLOGY 


The  factors  involved  in  the  formation  of  adsorption  or  absorption 
combinations  are  therefore  : 

(1)  Extent  of  surface.  In  a  colloidal  solution  this  must  be 
enormous  in  proportion  to  the  mass  of  substance  in  solution.  Thus 
a  10  c.c.  sphere  with  a  surface  of  22  sq.  cm.,  if  reduced  to  a  jfiiie  powder 
consisting  of  spherules  of  "00000025  cm.  in  diameter,  will  have  a 
surface  of  20,000,000  sq.  cm.,  i.e.  nearly  half  an  acre.  At  the  whole 
of  this  surface  adsorption  may  take  place,  involving  the  concentration 
of  dissolved  electrolytes,  ions,  or  gases. 

(2)  Chemical  nature  of  particle. 

(3)  Electric  charge  on  the  surface.  The  sign  of  this  may  be  deter- 
mined by  the  chemical  nature  of  the  colloid  and  its  relation  to  the 
electrolytes  in  the  surrounding  medium. 

Another  factor  which  may  determine  the  character  of  the  charge  on  the 
particles  has  been  pointed  out  by  Coehn.  This  observer  finds  that,  when  various 
non-conducting  bodies  are  immersed  in  fluids  of  different  dielectric  constants, 
they  assume  a  positive  or  negative  charge  according  as  their  own  dielectric 
constants  are  higher  or  lower  than  the  fluid  with  which  they  are  in  contact. 
For  instance,  glass  (5  to  6)  is  negative  in  water  (80)  or  alcohol  (26),  whereas  in 
turpentine  (2-2)  it  is  positive.  In  water,  as  Quincke  has  found,  nearly  all  non- 
conducting bodies  take  on  a  negative  charge.  Among  these  are  cotton-wool 
and  silk.  Particles  of  these  in  water,  exposed  to  an  electric  field,  move  towards 
the  anode.     The  same  is  true,  as  BayUss  has  shown,  of  paper. 

The  conditions  which  determine  the  formation  of  these  adsorption 
compounds  can  be  studied  in  their  simplest  form  on  the  adsorption 
of  dyestuffs  by  substances  such  as  paper.  If  we  take  a  series  of 
solutions  of  a  dye,  such  as  Congo-red,  in  progressively  diminishing 
concentration,  and  place  in  each  solution  the  same  amount  of  filter- 
paper,  we  find  that  a  part  of  the  dye  is  taken  up  by  the  paper,  and  the 
proportion  taken  up  is  larger  the  more  dilute  the  solution.  This 
relation  has  been  spoken  of  by  Bayliss  as  the  law  of  adsorption. 
This  is  illustrated  by  the  following  Table  of  results  of  such  an 
experiment  : 


ConcL'iitra 

ion  of 

l'ioi>ortion  of  dye 

Proportion  of  dye 

soliiti 

III 

in  solution 

in  papt-r 

Initial 

Final 

Per  cent. 

Per  cent. 

0014 

0-0056 

40 

60 

0012 

0-0024 

20 

80 

O-OIO 

0-0009 

9-3 

90-7 

0-008 

0-0003 

4 

96 

0-000 

0-00008 

1-3 

98-7 

0-004 

— 

trace 

practically  all 

0-002 

^^ 

traco 

practically  all 

If  put  into  the  form  of  a  curve,  where  the  ordinates  represent  the 


THE  PROPERTIES  OF  COLLOIDS  165 

percentage  of  dve  left  in  solution,  and  the  abscissae  the  original  con- 
centration of  the  solution,  the  curve  only  approaches  the  axis  {i.e. 
zero  concentration)  asymptotically.  In  other  words,  however  dilute 
the  original  solution  may  be,  there  will  always  be  a  certain  amount 
of  the  dye  left  unabsorbed  by  the  paper.  Similar  relations  are  found 
to  exist  between  proteins  and  electrolytes.  By  continuously  washing 
a  protein  or  gelatin  with  distilled  water,  the  removal  of  electrolytes 
becomes  slower  and  slower,  but  it  is  practically  impossible  within 
finite  time  to  get  rid  in  this  way  of  the  last  traces  of  ash. 

Although,  therefore,  the  chemical  behaviour  of  colloids  is  largely 
determined  by  surface  phenomena,  it  presents  at  the  same  time 
analogies  with  more  strictly  chemical  reactions,  since  it  is  conditioned 
by  the  chemical  structure  of  the  colloid  molecule  as  well  as  by  the 
charge  carried  by  the  latter.  A  good  example  of  these  adsorption 
combinations  is  presented  by  globulin,  the  behaviour  of  which  has 
been  studied  by  Hardy.  This  may  be  obtained  from  diluted  blood- 
serum  by  precipitation  with  acetic  acid.  Four  states  can  be  recog- 
nised in  both  the  solid  condition  and  in  solution,  viz.  globulin  itself, 
compounds  with  acid  or  with  alkali,  and  compounds  with  neutral  salt. 
The  amount  of  acid  and  alkali  combining  with  the  globulin  is  indeter- 
minate, the  effect  of  adding  either  acid  or  alkali  to  the  neutral  globulin 
being  to  cause  a  gTadual  conversion  of  an  oqaque,  milky  suspension 
into  a  limpid,  transparent  solution.  On  drying  HCl  globulin,  the 
dried  solid  is  found  to  contain  all  the  chlorine  used  to  dissolve  it. 
The  acid  may  therefore  be  regarded  as  being  in  true  combination. 
Both  acid  and  alkali  globulins  act  as  electrolytes,  the  globulin  being 
electrically  charged  and  taking  part  in  the  transport  of  electricity.  In 
order  to  produce  the  same  extent  of  solution,  the  concentration  of 
the  alkali  added  must  be  double  that  of  the  acid.  The  relation  of 
globuHn  to  acids  and  alkalies  is  similar  to  that  of  the  so-called  ampho- 
teric substances,  such  as  the  amino-acids.  An  amino-acid,  such  as 
glycine,  can  react  as  a  basic  anhydride  with  other  acids,  thus  : 

NH2  /NHaHCl 


CHg/  +  HGl  =  CH< 

^COaH  CO2H 

or  as  an  acid  anhydride  with  bases  : 

CH2.NH2  CH2.NH, 

I  +NaHO=   I  +H2O 

COOH  COONa 

Like  these  too,  globulin  forms  soluble  compounds  with  neutral  salts. 
An  amphoteric  electrolyte  thus  acts  as  a  base  in  the  presence  of  a 
strong  acid,  and  as  an  acid  in  the  presence  of  a  strong  base. 

From  true  electrolytes,  colloidal  solutions  differ  in  the  fact  that 


166  PHYSIOLOGY 

their  particles  are  of  varying  size  according  to  the  conditions  in  which 
they  exist,  and  carry  varying  charges  of  electricity,  whereas  an  ion 
such  as  Na  or  CI  has  a  mass  which  is  ccnstant  for  the  ion  in  question, 
and  always  carries  the  same  electric  charge.  The  charged  particles  of  an 
acid-  or  alkali- globulin  may  be  distinguished  therefore  as  fseudo-ions. 
In  these  adsorption  combinations,  although  the  chemical  nature  of 
the  colloidal  molecules  is  concerned,  there  is  an  absence  of  definite 
equihbrium  points,  such  as  we  are  accustomed  to  in  most  chemical 
reactions.  The  inertia  of  the  system  and  the  large  size  of  the  molecules 
determine  the  occurrence  of  false  equilibria  and  of  delayed  reaction, 
so  that  the  condition  and  behaviour  of  a  colloidal  system  at  any 
moment  are  determined,  not  entirely  by  the  quantitative  relations 
of  its  components,  but  also  by  the  past  history  of  the  system. 

COMBINATIONS  BETWEEN  COLLOIDS 
Besides  the  compounds  between  colloids  and  electrolytes,  com- 
bination, or  at  least  interaction,  takes  place  between  different  col- 
loids. Many  colloids  are  precipitated  by  other  colloidal  solutions. 
This  effect  is  always  found  to  occur  when  the  colloidal  solutions 
carry  different  charges.  Thus  ferric  hydrate  in  colloidal  solution 
is  precipitated  by  colloidal  sihca  or  colloidal  gold,  both  colloids  being 
thrown  out  of  solution.  On  the  other  hand,  certain  colloids  may 
exercise  a  protective  influence  on  other  colloidal  solutions.  Thus, 
as  Faraday  first  showed,  colloidal  gold  is  much  more  stable  in  the 
presence  of  a  little  gelatin.  The  colloids  of  serum  can  dissolve  a 
considerable  amount  of  purified  globulin.  Although  the  latter  in 
solution  shows  a  drift  in  the  electric  field,  the  resulting  solution  is 
quite  unaffected  by  the  passage  of  a  current  through  it.  In  these 
cases  the  protective  colloids  carry  no  charge,  but  the  same  protective 
effect  may  be  observed  if  a  large  excess  of,  e.g.  an  electro-positive 
colloid  be  added  to  an  electro -negative  colloid.  This  interaction 
between  different  colloids  probably  plays  an  imjDortant  part  in  many 
physiological  phenomena.  We  have  reason  to  believe  that  the  re- 
actions between  toxin  and  antitoxin,  between  ferment  and  substrate, 
which  w^e  shall  study  later,  are  of  this  character,  and  that  the  com- 
pounds formed  belong  to  the  class  of  adsorption  combinations. 

THE  COAGULATION  OF  COLLOIDS 
Most  colloidal  solutions  are  unstable,  and  the  relations  between  the 
suspended  particle  or  molecule  and  the  surrounding  fluid  may  be 
upset  by  slight  (hanges  of  reaction  or  the  presence  of  minute  traces 
of  salts.  As  a  result  the  hydrosol  is  destroyed,  the  suspended  par- 
ticles aggregating  to  form  larger  complexes.  These  aggregations  may 
settle  to  the  bottom  of  the  fluid  as  a  precipitate,  or  may  form  a  species 


THE  PROPERTIES  OF  COLLOIDS  167 

of  network,  the  result  varying  according  to  the  nature  of  the  coUoid 
and  its  concentration.  Thus  gelatin  changes  from  the  condition  of 
hydrosol  to  hydrogel  with  fall  of  temperature.  The  same  is  true  of 
agar.  On  the  other  hand,  by  adding  calcium  chloride  to  an  alkahne 
solution  of  casein,  we  obtain  a  mixture  which  sets  to  a  jelly  on  warming, 
but  becomes  fluid  again  on  cooling.  Other  agencies  may  lead  to  the 
production  of  changes  which  are  irreversible.  Thus  a  strong  solution 
of  colloidal  silica  sets  to  a  solid  jelly  on  the  addition  of  a  trace  of  neutral 
salt,  and  it  is  not  possible  to  reform  the  hydrosol,  however  long  the 
jelly  is  ..ubmitted  to  dialysis. 

Two  methods  of  bringing  about  coagulation  of  hydrosols  deserve 
special  mention.  The  first  of  these  is  heat- coagulation.  If  a  solution 
of  egg- albumin  or  globulin  be  heated  in  neutral  or  slightly  acid  medium 
and  in  the  presence  of  neutral  salt,  the  whole  of  it  is  thrown  down 
in  an  insoluble  form.  This  coagulated  protein  is  insoluble  in  dilute 
acids  or  alkalies.  The  same  coagulative  efEect  of  heating  is  observed 
in  the  metallic  sols.  With  concentrated  solutions  of  protein,  heat 
coagulation  results  in  the  formation  of  a  gel,  i.e.  a  network  of  insoluble 
protein,  containing  water  or  a  very  dilute  solution  of  protein  in  its 
meshes.  In  dilute  solutions  the  result  is  the  production  of  a  floccu- 
lent  precipitate. 

Another  method  is  the  so-called  mechanical  coagulation.  If  a 
solution  of  globulin  or  albumin  be  introduced  into  a  bottle,  which  is 
then  violently  shaken,  a  shreddy  precipitate  makes  its  appearance  in 
the  solution,  and  this  precipitate  increases,  so  that  by  prolonged 
shaking  it  is  possible  to  throw  down  80  or  90  per  cent,  of  the  dissolved 
protein  in  the  coagulated  form.  Ramsden  has  shown  that  this 
mechanical  coagulation  is  a  surface  phenomenon.  It  depends  on  the 
fact  that  a  large  number  of  substances  in  solution  (viz.  any  which 
lower  the  surface  tension  of  their  solutions)  midergo  concentration 
at  the  free  surface  of  the  fluid.  Such  substances  are  proteins,  bile- 
salts,  quinine,  saponin,  &c.  In  the  case  of  proteins  the  concentra- 
tion reaches  such  an  extent,  and  the  molecules  at  the  surface  are 
so  closely  packed  together,  that  they  form  an  actual  soHd  pelhcle, 
which  hinders  the  movement  of  any  object,  such  as  a  compass  needle, 
suspended  in  the  surface.  When  the  solution  is  violently  shaken,  new 
surfaces  are  constantly  being  formed,  and  as  the  older  smlaces  are 
withdrawn  into  the  fluid,  the  solid  pellicle  on  them  is  rolled  up  into 
a  fine  shred  of  coagulated  protein,  and  this  process  will  continue  until 
there  is  no  protein  left  to  form  a  pellicle. 

We  must  conclude  that  colloidal  solutions,  although  diflering 
so  widely  from  true  solutions  in  many  of  their  properties,  are  con- 
nected with  these  by  all  possible  grades.  In  a  solution  of  an  ordinary 
crystalloid  or  electrolyte  the  molecules  of  the  dissolved  substance  are 


168  PHYSIOLOGY 

distributed  equally  and  homogeneously  among  the  molecules  of  the 
solvent.  In  the  various  grades  of  solution  a  colloid  solution  or 
hydrosol  may  be  assumed  to  begin  when  the  size  of  the  molecule  is 
increased  out  of  all  proportion  to  that  of  the  molecules  of  the  solvent. 
The  '  dissolved '  molecules  now  begin  to  have  the  properties  of 
matter  in  mass  and  to  present  surfaces  with  all  their  attendant 
attributes.  The  same  sort  of  solution  may  be  formed  with  smaller 
molecules,  such  as  SiOg,  when  these  are  aggTegated  together  with 
adsorbed  water  into  huge  molecular  complexes,  or,  as  in  metallic  sols, 
by  the  division  of  the  solid  metal  into  ultra-microscopic  particles.  The 
distinguishing  features  of  a  colloidal  solution  are  due  to  this  lack  of 
homogeneity,  and  to  the  fact  that  in  every  solution  there  are  two 
phases — a.  fluid  phase,  and  a  second  phase,  which  is  either  sohd  or  a 
concentrated  or  supersaturated  solution  of  the  colloid.  The  huge 
size  of  the  molecules  and  the  development  of  surface  not  only  determine 
the  formation  of  adsorption  combinations,  but,  on  account  of  the 
inertia  of  the  system,  cause  a  delay  in  changes  of  state,  and  tend  to 
the  formation  of  false  equilibria  dependent  on  the  past  history  of  the 
system. 

IMBIBITION 

All  colloids,  even  those  such  as  starch  or  gelatin,  which  are  insoluble 
in  cold  water,  exhibit  a  j)henomenon,  viz.  '  Quellung  '  or  imbibition, 
which  in  many  cases  it  is  impossible  to  distinguish  from  the  process  of 
solution.  This  phenomenon,  which  was  long  ago  studied  by  Chevreul 
and  has  lately  been  the  subject  of  a  series  of  careful  experiments  by 
Overton,  is  exhibited  by  all  animal  tissues  and  all  colloids.  Thus 
elastic  tissue  dried  in  vaxiuo  absorbs  from  a  saturated  solution  of 
common  salt  36-8  per  cent,  of  water  and  salt.  If  dried  colloids  be 
suspended  in  a  closed  vessel  over  various  solutions,  they  will  take  up 
water  in  the  form  of  vapour  from  the  solution,  and  the  osmotic  pres- 
sure of  the  solution  in  question  will  inform  us  as  to  the  amount  of  work 
which  would  be  necessary  in  order  to  separate  the  water  again  from 
the  colloids. 

Thus  it  has  been  reckoned  that  to  press  out  water  from  gelatin 
containing  284  parts  of  water  to  100  parts  of  dried  gelatin  would 
require  a  pressure  of  over  two  hundred  atmospheres.  The  imbibition 
pressure  of  colloids  increases  rapidly  with  the  concentration  of  the 
colloid  and  at  a  greater  rate  than  the  latter.  In  this  respect,  however, 
imbibition  pressure  resembles  osmotic,  or  indeed  gaseous,  pressure.  At 
extreme  pressures  the  pressure  of  hydrogen  rises  more  rapidly  than 
its  volume  diminishes.  In  solutions  this  effect  is  more  marked  the 
larger  the  size  of  the  molecule.  Thus  a  6-7  per  cent,  solution  of  cane 
sugar  has  the  same  vapour- tension,  and  therefore  the  same  osmotic 


THE  PROPERTIES  OF  COLLOIDS  169 

pressure,  as  a  '67  per  cent.  NaCl  solution.  A  67  per  cent,  cane-sugar 
solution  has,  however,  the  same  osmotic  pressure  as  an  18|  per  cent, 
solution  of  common  salt.  It  is  impossible,  therefore,  to  draw  any 
hard  line  of  distinction  between  imbibition  pressure  and  osmotic 
pressure  In  the  same  way  it  is  impossible  to  say  where  a  fluid  ceases 
to  be  a  solution  and  becomes  a  suspension.  All  grades  are  to  be  found 
between  a  solution  such  as  that  of  common  salt  with  a  high  osmotic 
pressure  and  optical  homogeneity,  and  a  solution  such  as  that  of 
starch,  which  scatters  incident  light  and  is  therefore  opalescent,  and 
has  no  measurable  osmotic  pressure. 

The  close  connection  between  the  processes  of  imbibition  and  of 
solution  is  shown  also  by  the  fact  that  the  latter  occurs  only 
in  certain  media,,  the  nature  of  the  media  being  dependent  on  the 
chemical  character  of  the  substances  in  question.  Thus  all  the  crystal- 
line carbohydrates — -such  as  grape  sugar  and  cane  sugar — are  easily 
soluble  in  water,  only  shghtly  soluble  in  alcohol,  and  practically 
insoluble  in  ether  and  benzol.  The  amorphous  carbohydrates,  which 
must  be  regarded  as  derived  by  a  process  of  condensation  from  the 
crystalhne  carbohydrates — e.g.  starch,  cellulose,  gum  arable,  &c. — 
have  a  strong  power  of  imbibition  for  water.  This  power  may  be 
limited,  as  in  the  case  of  cellulose,  or  may  be  unlimited,  as  in  the  case 
of  gum  arable,  so  that  a  so-called  solution  results.  On  the  other  hand, 
they  swell  up  but  slightly  in  alcohol,  and  are  unaffected  by  ether  and 
benzol.  In  the  same  way  proteins  all  take  up  water,  and  in  many  cases 
form  a  so-called  solution,  but  are  unaffected  by  ether  and  benzol — b, 
behaviour  which  is  repeated  in  the  case  of  the  amino-acids,  out  of 
which  the  proteins  are  built  up,  and  which  are' easily  soluble  in  water, 
but  are  practically  insoluble  in  ether  and  benzol.  On  the  other  hand, 
india-rubber  and  the  various  resins  take  up  ether,  benzol,  and  tur- 
pentine often  to  an  indefinite  extent,  while  they  are  untouched  by 
water.  With  this  behaviour  we  may  compare  the  easy  solubility  of 
the  hydrocarbons,  the  aromatic  acids,  and  esters  in  ether  and  benzol, 
and  their  insolubility  in  water.  As  Overton  has  pointed  out,  the  power 
of  amorphous  carbohydrates  to  take  up  fluids  is  modiiied  by  alteration 
of  their  chemical  structure  in  the  same  direction  as  the  solubility 
of  the  corresponding  crystalline  carbohydrates.  Thus,  if  the  hydroxyl 
groups  in  the  siigars  be  replaced  by  nitro,  acetyl,  or  benzoyl  groups, 
they  become  less  soluble  in  water,  while  their  solubility  in  alcohol, 
acetone,  &c.,  is  increased.  In  the  same  way  the  replacement  of  the 
hydroxyl  groups  in  cellulose  by  NO2  groups  diminishes  the  power 
possessed  by  this  substance  of  taking  up  water,  but  renders  it  capable 
of  swelling  up  or  dissolving  in  alcohol  and  acetone. 


SECTION  IV 

THE  MECHANISM  OF  CHEMICAL  CHANGES   IN 
LIVING  MATTER.     FERMENTS 

All  the  events  wliicli  make  up  the  life  of  plants  and  animals  are 
accompanied  and  conditioned  by  chemical  changes  of  the  most  varied 
character.  In  a  previous  chapter  we  have  endeavoured  to  form  an 
•  idea  of  the  ways  in  which  some  of  the  synthetic  processes  that  occur 
in  the  living  body  may  be  efiected.  We  saw  that,  although  it  was 
possible  to  imitate  in  many  respects  the  vital  syntheses  by  ordinary 
laboratory  methods,  the  imitation  fell  far  short  of  the  process  as  it 
actually  occurs  in  the  living  cell,  both  in  completeness  of  the  reaction 
and  in  the  ease  with  which  it  could  be  effected.  We  can,  for  instance, 
by  passing  carbon  dioxide  over  red-hot  charcoal,  convert  it  into  carbon 
monoxide,  and  this  gas,  acting  on  dry  potassium  hydrate,  forms 
potassium  formate.  Formate  of  hme,  on  dry  distillation,  gives  a  small 
proportion  of  formaldehyde  which,  under  the  influence  of  dilute 
alkaUes,  will  condense  to  the  mixture  of  sugars  known  as  acrose.  The 
green  leaf  in  sunlight  absorbs  the  minimal  quantities  of  carbon  dioxide 
present  in  the  atmosphere  and  converts  it  almost  quantitatively  into 
starch  within  a  few  minutes,  and  this  change  is  effected  in  the  absence 
of  any  concentrated  reagents  and  at  the  ordinary  temperature  of  the 
atmosphere.  Many  of  the  chemical  transformations  effected  by  living 
cells  we  have  so  far  been  quite  unable  to  imitate.  The  problem  of  the 
synthesis  of  camphor,  of  the  terpenes,  of  starch,  of  -cellulose,  is  still 
unsolved,  and  even  in  the  case  of  those  substances  which  we  can 
manufacture  outside  the  living  cell  our  methods  involve  the  use  of 
powerful  reagents  and  of  high  temperatures,  and  result  in  most  cases 
in  the  production  of  many  side  reactions,  besides  that  which  it  is  our 
special  object  to  imitate.  The  distinguishing  characteristics  of  the 
chemical  changes  wrought  by  the  living  cell  are  : 

(1)  The  rapidity  with  which  they  are  effected  at  ordinary  tem- 
peratures. 

(2)  The  specific  direction  of  the  process,  which  is  therefore  almost 
complete,  with  a  surprising  absence  of  the  side  reactions  which  inter- 
fere to  such  an  extent  with  the  yield  of  the  methods  employed  in  a 
chemical  laboratory. 

This  second  characteristic  may,  however,  be  regarded  as  a  con- 
sequence of  the  first,  since  an  increase  in  the  velocity  of  any  given 

170 


CHEMICAL  CHANGES  IN  LIVING  MATTER.   FERMENTS    171 

reaction  will  determine  a  preponderance  of  this  reaction  over  all  other 
possible  ones.  A  fundamental  question,  therefore,  in  physiology  must 
relate  to  the  manner  in  which  the  cell  is  able  to  influence  the  velocity 
of  some  specific  reaction. 

In  spite  of  the  enormous  diversity  of  chemical  reactions  occurring 
in  the  body,  they  may  be  divided  into  a  relatively  small  number  of 
types.  Nearly  all  the  reactions,  are  reversible.  The  chief  types  of 
chemical  change  are  as  follows  : 

(1)  HYDROLYSIS.  In  most  cases  this  involves  the  taking  up  of 
water  and  a  decomposition  into  smaller  molecules.  Thus  the  proteins 
are  broken  down  in  the  intestine  into  their  constituent  amino-acids. 
The  disaccharides,  such  as  maltose  or  lactose,  take  up  one  molecule 
of  water  and  give  rise  to  two  molecules  of  monosaccharide.  The  fats 
take  up  three  molecules  of  water  with  the  formation  of  fatty  acid 
and  glycerin.  Hippuric  acid  is  broken  down  into  benzoic  acid  and 
glycine.  The  reverse  change,  that  of  dehydration,  is  also  effected, 
apparently  with  equal  facility,  by  the  living  cell,  the  hexoses  losing 
water  and  being  converted  into  a  complex  starch  or  glycogen  molecule, 
while  the  amino-acids  are  built  up  first  into  polypeptides,  and  these 
again  into  the  complex  proteins  of  the  cell.  Besides  the  reactions  in 
which  there  is  a  difference  in  the  amount  of  free  water  on  the  two 
sides  of  the  equation,  it  seems  probable  that  hydrolysis  and  simul- 
taneous dehydrolysis  at  different  parts  of  the  molecule  determine  a 
number  of  chemical  transformations,  which  at  first  sight  seem  to 
involve  a  simple  splittmg  of  the  molecule.  An  example  of  such  a 
process  is  afforded  by  the  conversion  of  glucose  into  lactic  acid  described 
on  p.  128. 

(2)  DEAMINATION.  This  process  involves  the  splitting  off  of  an  NHg 
group  from  an  amino-acid  as  ammonia,  and  its  replacement  by  H  or  OH. 
Many  tissues  of.  the  body  appear  to  have  this  power.  In  most  cases 
the  nature  of  the  change  in  the  remaining  fatty  moiety  of  the  molecule 
has  not  yet  been  ascertained.  If,  for  instance,  to  a  mass  of  liver  cells 
some  amino-acid,  such  as  glycine,  alanine,  or  leucine,  be  added,  ammonia 
is  set  free  in  proportion  to  the  amount  of  amino-acid  which  was  added. 
This  ammonia  is  therefore  assumed  to  be  derived  from  the  amino-acid, 
and  it  has  been  suggested  that  here  also  the  process  of  splitting  off 
ammonia  is  a  hydrolytic  one  and  that  the  NHg  gi"oup  is  replaced  bv 
OH.    Tlms- 

CH,  CH, 


CH.NH2  +  H2O  -  CH.OH  +  NH 

I  I 

COOH  COOH 

(nlanino) 


172  PHYSIOLOGY 

Recent  work  by  Neubaiier  tends  to  show  that  deamination  is 
accompanied  in  the  first  place  by  oxidation,  so  that  the  first  inter- 
mediate product  formed  is  not  an  a  oxy-acid,  but  an  a  ketonic  acid.  A 
second  atom  of  oxygen  is  then  taken  up,  and  carbon  dioxide  is  split 
off,  with  the  production  of  the  next  lower  acid  of  the  series. 

We  might  represent  these  changes  as  follows  : 

(1)     CH3  CH3 

1  I 

C^NH.,  +  O  =  CO        +  NH3 

I  I 

COOH  COOH 


i:2)       C:H3 


CH3 


CO  +0=     I        +CO2 

I  COOH 

COOH 

Is  the  reverse  change  ever  effected  in  the  animal  body  ?  If  it 
were  possible  to  replace  the  OH  gi'oup  in  an  oxy-fatty  acid  by  NHg  or 
the  0  in  an  a  ketonic  acid  by  HNHo,  it  ought  also  to  be  possible  to 
nourish  an  animal  from  a  mixture  of  carbohydrates  and  ammonia, 
or  at  any  rate  by  supplying  him  with  a  mixture  of  the  appropriate 
oxy-acids  or  ketonic  acids  and  ammonia.  Until  recently  there  was 
no  evidence  that  the  animal  body  is  able  to  utilise  nitrogen,  except 
in  organic  combination  as  amino-acids  or  the  complex  aggregate  of 
amino-acids  known  as  proteins.  In  the  plant  the  process  of  synthesis 
of  protein  from  ammonia  and  a  carbohydrate  such  as  hexose  is  con- 
tinuously going  on,  and  it  is  probable  that  the  formation  of  amino- 
acid  occurs  by  a  process  the  reverse  of  that  which  we  have  just  been 
studying.  Knoop  has  shown  that  the  same  reversed  change  may  occur 
even  in  a  mammal,  and  that  here  again  the  intermediate  substance  is  an 
a  ketonic  acid.  On  administering  benzylpyrotartaric  acid  (CgHg. 
CHg.CHg.CO.COOH)  to  a  dog,  a  certain  amount  of  benzylalanine 
(CeH5.CH,.CH2.CHNH2.COOH)  appeared  in  the  urine.  The  first 
phase  of  the  oxidative  deamination  of  amino-acids  is  thus  a  reversible 
one  and  may  be  represented  : 


R 

R 

OH 

R 

1 

CHNH2  +  0        =r 

c<            - 

NH2 

CO  +  NH 

COOH 

COOH 

COOH 

(3)  DECARBOXYLATION.     Many  amino-acids  when  subjected  to 


CHEMICAL  CHANGES  IN  LIVING  GUTTER.   FERMENTS    173 

the  agency  of  bacteria  lose  a  molecule  of  carbon  dioxide  and  are 
converted  into  a  corresponding  amine. 

For  instance,  lysine,  which  is  diamino-caproic  acid,  is  converted  into 
pentamethylene  diamine  or  cadaverine.     Thus  : 

CH2.NH2  CH2.NH2 

I  I 

CH.  CHj 

I     "  I 

CH.,  becomes  CHj 

1  "  I 

CH2  CH2 

I  I 

CH.NHo  CH2.NH2 

1 
COOH 

In  the  same  way  ornithine  derived  from  the  breakdown  of  arginine  is 
converted  by  putrefactive  bacteria  into  tetra-methylene  diamine  or 
putrescine.    Other  examples  of  this  process  of  decarboxylation  are  : 

Isoamylamine  from  leucine,  (CTl3)2.CH.CH2.CH2.NH2. 

/3  phenylethylamine  from  phenylalanine,  CgHj.CHa.CHj.NHg. 

Para,  oxyphenylethylamine  from  t\TOsine,  OH.C6H4.CH2.CH2.NH2. 

A  similar  process  has  been  supposed  to  take  place  as  a  step  in  the 
successive  oxidation  of  the  carbon  atoms  in  the  long  chain  fatty  acids 
or  carbohydrates,  but  a  thorough  study  of  this  process  as  it  occurs 
in  the  higher  animals  is  still  wanting,  and  its  very  existence  is  indeed 
still  hypothetical.  In  the  case  of  the  fats  the  oxidation  takes  place 
chiefly  or  entirely  in  the  p  position.  On  the  other  hand,  decarboxyla- 
tion certainly  takes  place  in  substances  such  as  the  a  amino-acids, 
where  the  first  oxidation  change  occurs  in  the  a  group,  and  probably 
closely  follows  this  oxidation  change.  The  reverse  reaction,  namely, 
the  insertion  of  the  group  CO.O  at  the  end  of  the  long  carbon  chain, 
is  not  known  to  take  place.,  but  would  furnish  a  means  by  which  the 
organism  with  apparent  simphcity  could  build  up  long  carbon  chains 
and  so  imitate  the  process  which  in  the  laboratory  is  generally  effected 
by  attaching  a  CN  group  to  the  end  of  the  molecule.  In  the  case  of  the 
fats  the  building  up,  like  the  oxidative  breakdown,  appears  to  occur 
by  two  carbon  atoms  at  a  time  ;  hence  all  the  fatty  acids  met  with  in 
the  body  have  an  even  number  of  carbon  atoms  in  their  chain. 

It  is  worthy  of  note  that  all  the  changes  which  we  have  been 
considering — changes  which  not  only  account  for  the  greater  part  of 
the  chemical  reactions  of  the  U\ang  body,  but  may  lead  to  the  produc- 
tion of  the  most  complex  substances  known — are  performed  with  little 


174 


PHYSIOLOGY 


expenditure  or  evolution  of  energy.  This  is  evident  if  we  examine  the 
heat  evolved  by  the  total  combustion  of  one  gramme  molecule  of  the 
initial  and  final  substances  in  a  number  of  typical  reactions.  In  the 
following  Table  these  are  given  for  the  substances  involved  in  typical 
instances  of  the  three  classes  of  chemical  change  that  we  have  just 
been  considering : 

(1)  Hydrolysis 


Initial 
substance 

Heat  of  com- 

Heat 

bustion  per 
gram  molecule 

Final 
substance 

of 

combustion 

Maltose 

.       1350 

2  Glucose     . 

1354 

Ghicose 

677 

2  Lactic  acid 

659 

Hippuric  acid 

.       1013 

/  Glycine     . 

2351  1008 

\  Benzoic  acid 

773  1  ^"" 

(2)  Deamination 

Initial 

Heat  of 

Final 

Heat  of 

substance 

combustion 

substance 

combustion 

Alanine 

389-2 

Lactic  acid 

329-5 

Leucine 

855 

Caproic  acid 

837 

Aspartic  acid 

386 

Succinic  acid 

354 

(3)  Decarboxylation 

Initial 

Heat  of 

Final 

Heat  of 

substance 

combustion 

substance 

combustion 

Alanine 

389 

Ethylamine . 

409 

Leucine 

855 

Amylamine . 

867 

(4)  OXIDATION  AND  REDUCTION.  The  fourth  class  of  chemical 
reactions  differs  from  those  just  described  in  being  attended 
with  a  very  considerable  energy  change.  This  class  involves  the 
processes  of  oxidation  and  reduction.  In  almost  every  living  cell 
by  far  the  largest  amount  of  the  energy  available  for  the  discharge 
of  the  functions  of  the  cell  is  derived  from  the  oxidation  of  the 
food-stuffs,  and  even  in  the  plant  the  energy  is  obtained  from  the 
oxidation  of  the  food-stuffs,  built  up  in  the  first  instance  at  the 
cost  of  the  energy  of  the  sun's  rays.  If  we  take  the  final  changes 
in  the  food-stuffs,  the  very  large  evolution  of  energy  attending 
their  oxidation  is  at  once  apparent.  Thus  in  the  conversion 
of  glucose  into  COg  and  water  there  is  an  evolution  for  each 
gramme  molecule  of  677  calories.  In  the  combustion  of  glycerin  397 
calories  are  evolved.  In  the  oxidation  of  a  fat  such  as  trimjnristin 
there  are  6650  calories  evolved.  The  change  does  not,  in  the  living  cell, 
occur  all  at  once,  but  the  molecule  is  oxidised  step  by  step.  In  each  step 
the  heat  change  will,  however,  be  probably  greater  than  the  heat  changes 
in  the  other  types  of  chemical  change  which  we  have  been  considering. 

Since  the  mechanism  of  oxidation  in  the  animal  body  will  have  to 
be  discussed  at  length  in  a  subsequent  part  of  this  work,  we  may  at 
present  confine  our  attention  to  the  other  types  of  chemical  change. 


CHEMICAL  CHANGES  IN  LIVING  MATTER.   FERMENTS    175 

Of  these,  all  which  involve  a  splitting  of  a  large  molecule  into  smaller 
ones  with  the  taking  up  of  one  or  more  molecules  of  water,  as  well  as, 
in  all  probability,  those  in  which  the  reverse  change  of  dehydration 
and  synthesis  occur,  are  effected  in  the  body  by  means  of  ferments. 
To  the  same  agency  are  also  ascribed  the  process  of  deamination, 
which  takes  place  in  many  organs  of  the  body,  and,  though  with  less 
certainty,  the  processes  which  involve  decarboxylation. 

FERMENTS 

Under  the  name  ferments  we  include  a  number  of  substances  of 
indefinite  composition  whose  existence  is  chiefly  known  to  us  by 
their  action  on  other  substances.  A  ferment  has  been  defined  as  a 
body  which  on  addition  to  a  chemical  system  is  able  to  effect  changes 
in  this  system  without  supplying  any  energy  to  the  reaction,  without 
being  used  up,  and  without  taking  any  part  in  the  formation  of  the 
end  products.  It  differs  therefore  from  the  reacting  substances  in 
the  absence  of  any  strict  quantitative  relationships  between  it  and 
the  substances  included  in  the  system  in  which  its  effects  are  produced. 
Minimal  quantities  of  ferment  can  induce  chemical  changes  involving 
almost  indefinite  quantities  of  other  substances,  the  only  result  of  in- 
creasing the  quantity  of  ferment  being  to  quicken  the  rate  of  the  change. 
Since  they  are  effective  in  minimal  doses  they  occur  in  hving  tissues 
in  minute  quantities,  and  it  is  partly  due  to  this  fact  that  it  has  hitherto 
proved  impossible  to  obtain  any  preparation  of  a  ferment  which  could 
be  regarded  as  a  pure  substance.  The  difficulty  in  their  isolation 
is  increased  by  the  fact  that  all  of  them  are  colloidal  or  semi- 
colloidal  in  character,  and  present,  therefore,  the  tendency  common  to 
all  colloids  of  adhering  to  other  colloidal  matter  as  well  as  to  surfaces 
such  as  those  presented  by  a  precipitate.  A  common  method  of  isolat- 
ing, or  rather  obtaining  a  concentrated  preparation  of  a  ferment  is  to 
produce  in  its  solution  an  inert  precipitate  such  as  cholesterin  or 
calcium  phosphate.  The  ferment  is  carried  down  on  the  precipitate 
and  may  be  obtamed  in  solution  on  washing  the  precipitate  with 
water.  A  further  difficulty  in  their  preparation  lies  in  the  unstable 
character  of  many  members  of  the  group.  Although  they  are  not 
coagulated  by  alcohol,  they  are  nevertheless  gradually  changed,  so 
that  every  act  of  precipitation  of  a  ferment  tends  to  rob  it  of  some  of 
its  powers,  i.e.  of  the  only  characteristic  by  which  we  can  establish 
its  identity. 

Of  these  ferments  a  large  number  have  already  been  described 
as  taking  part  in  the  ordinary  chemical  processes  of  life.  So  wide 
is  their  dominion  in  cell  chemistry  that  many  physiologists  have 
thought  that  the  whole  of  life  is  really  a  continual  series  of  ferment 
actions.     The  following  list  represents  some  of  the  ferments  whose 


17G  PHYSIOLOGY 

existence  has  been  definitely  established  in  the  animal  body.  The 
greater  part  of  them  are  involved  in  the  processes  of  digestion  in  the 
ahmentary  canal.  The  preponderance,  however,  of  digestive  ferments 
in  the  list  is  due  to  the  fact  that  we  know  more  about  digestion  than 
about  the  other  chemical  processes  taking  place  within  the  cells 
of  the  body. 

List  of  Ferments 


Ferment 

Converting 

Into 

Amylase    (of    saliva,     pancreatic 

Starch 

Maltose  and  dextrin 

juice,  liver,  blood  serum,  &c.) 

Pepsin       ..... 

Proteins     . 

Proteoses   and   pep- 
tones 

Trypsin     ..... 

Proteins     . 

Peptones  and  amino- 
acids 

Enterokinase     .... 

Trypsinogen 

Trypsin 

Erepsin      ..... 

Proteoses 

Amino-acids 

Lipase  (of  pancreatic  juice,  liver. 

Neutral  fats 

Fatty       acid       and 

&c.) 

glycerin 

Maltase     ..... 

Maltose 

Glucose 

Lactase     ..... 

Milk  sugar 

Glucose  and  galactose 

Invertase  or  sucrase   . 

Cane  sugar 

Glucose    and    levu- 
lose 

Arginase  ..... 

Arginin 

Urea  and  ornithine 

Urease       ..... 

Urea 

Ammonium      carbo- 
nate 

Lactic  acid  ferment     . 

Glucose 

Lactic  acid. 

Zymase  (?  present  in  the  body)    . 

Glucose 

Alcohol  and  COg 

Deaminating  ferment  (?)  r.  p.  171 

Amino-acids 

Oxy-acids  ( ?) 

Many  other  ferments  will  probably  be  distinguished  with  increase 
in  our  knowledge  of  cellular  metabolism.  The  long  list  which  is  here 
given  suffices  to  show  how  great  a  part  these  bodies  must  play  in  the 
normal  processes  of  life.  A  study  of  the  conditions  of  ferment  actions 
is  therefore  essential  if  we  would  form  a  conception  of  the  chemical 
mechanisms  of  the  living  cell. 

It  is  important  to  note  that  all  the  changes  wrought  by  ferments 
can  be  effected  by  ordinary  chemical  means.  Thus  the  disaccharides 
can  be  made  to  take  up  a  molecule  of  water  and  undergo  conversion 
into  monosaccharides.  If  a  solution  of  maltose  be  taken  and  bacteria 
b^  excluded  from  the  solution,  it  undergoes  at  ordinary  temperatures 
practically  no  change.  If  the  solution  be  warmed,  a  slow  process  of 
hydration  takes  place  which  is  quickened  by  rise  of  temperature, 
so  that  if  the  solution  be  heated  under  pressure  to,  say,  1]0°C.,  hydrolysis 
occurs  with  considerable  rapidity.  If,  however,  a  little  maltase 
be  added  to  the  solution,  the  change  of  maltose  into  glucose  takes 


CHEMICAL  CHANGES  IN  LIVING  MATTER.   FERMENTS    177 

place  rapidly  at  a  temperature  of  30*^  C.  In  the  same  way  a  solution 
of  protein  may  be  kept  almost  indefinitely  without  undergoing 
hydrolysis,  which,  however,  can  be  induced  by  heating  the  solution 
under  pressure.  The  action  of  the  ferments  in  these  two  cases  is 
to  quicken  a  process  of  hydrolysis  which  without  their  presence 
would  take  an  infinity  of  time  for  its  accomplishment. 

In  this  respect  their  action  is  similar  to  that  of  acids,  and  indeed 
of  a  whole  class  of  bodies  which  are  spoken  of  as  catalysers  or  catalysts. 
A  catalyser  is  a  substance  which  will  increase  (or  diminish)  the  velocity 
of  a  reaction  without  adding  in  any  way  to  the  energy  changes 
involved  in  the  reaction,  or  taking  any  part  in  the  formation  of  the  end- 
products.  Since  the  catalyser  is  unchanged  in  the  process,  a  very 
small  quantity  is  able  to  influence  reactions  involving  large  quantities 
of  other  substances.  By  adding  acids  to  a  watery  solution  of  the 
food-stuffs,  the  process  of  hydrolysis  is  quickened  in  proportion  to 
the  strength  and  concentration  of  the  acid.  The  effective  catalytic 
agents  in  this  process  appear  to  be  the  hydrogen  ions  of  the  free  acid. 
There  are  many  other  bodies,  besides  the  free  acids,  which  may  act 
as  catalysers,  and  a  study  of  the  conditions  under  which  catalysis 
takes  place  may  throw  some  Light  on  the  essential  nature  of  the  action 
of  ferments. 

The  velocity  of  almost  any  reaction  in  chemistry  can  be  altered 
by  the  addition  of  some  catalytic  agent,  and  there  are  few  of 
the  ordinary  reactions  in  which  catalysis  does  not  play  some  part. 
Among  such  processes  we  may  instance  the  action  of  spongy  platinum 
on  hydrogen  peroxide.  Hydrogen  peroxide  undergoes  slow  spon- 
taneous decomposition  into  water  and  oxygen.  If  a  little  spongy 
platinum  be  added  to  it,  it  is  at  once  seen  to  decompose  rapidly  with 
the  evolution  of  bubbles  of  oxygen,  and  the  action  does  not  cease 
until  the  whole  of  the  hydrogen  peroxide  has  been  destroyed.  Spongy 
platinum  is  able  in  the  same  way  to  quicken  a  very  large  number  of 
chemical  reactions.  Thus  sulphur  dioxide  and  oxygen  when  heated 
together  will  combine  very  slowly  ;  the  combination  becomes  rapid  if 
a  mixture  of  the  two  gases  be  passed  over  heated  platinum.  The 
same  reaction,  namely,  the  combination  of  sulphur  dioxide  with 
oxygen,  may  be  quickened  by  the  addition  of  a  small  trace  of  nitric 
oxide,  and  this  fact  is  made  use  of  in  the  maimfactm-e  of  sulphuric 
acid  on  a  conmiercial  scale  by  the  ordinary  lead-chamber  process. 
Hydrogen  peroxide  and  hydriodic  acid  slowly  interact  with  the 
formation  of  water  and  iodine.  This  reaction  may  be  quickened  by 
the  addition  of  many  substances,  among  which  we  may  mention 
molybdic  acid. 

There  is  moreover  a  specificity  in  the  action  of  catalysers,  though 
not  so  well  marked  as  with  ferments.     Whereas  all  the  disaccharides 

12 


178  PHYSIOLOGY 

are  converted  by  acids  into  the  corresponding  monosaccliarides,  a 
ferment  such  as  invertase  acts  only  on  cane  sugar,  and  has  no 
action  on  maltose  or  lactose,  each  of  which  requires  a  specific  ferment 
(maltase,  lactase)  to  effect  their  '  inversion.'  But  we  find  many 
examples  of  a  restricted  action  even  among  inorganic  catalysers. 
Thus  potassium  bichromate  will  act  as  the  catalyser  for  the  oxida- 
tion of  hydriodic  acid  by  bromic  acid,  but  not  for  the  oxidation  of 
the  same  substance  by  iodic  acid.  Iron  and  copper  salts  in  minute 
traces  will  quicken  the  oxidation  of  potassium  iodide  by  potassium 
persulphate,  but  have  no  influence  on  the  com'se  of  the  oxidation  of 
sulphur  dioxide  by  potassium  persulphate.  Tungstic  acid  increases 
the  velocity  of  oxidation  of  hydriodic  acid  by  hydrogen  peroxide,  but 
has  no  effect  on  the  velocity  of  oxidation  of  hydriodic  acid  by  bromic 
acid,  and  these  examples  may  be  multiphed  to  any  extent.  One 
cannot  therefore  regard  the  limitation  of  action  of  the  ferments  as 
justifying  any  fundamental  distinction  being  drawn  between  the 
action  of  this  class  of  substances  and  catalysts. 

Whereas  the  influence  of  most  catalysers  on  the  velocity  of  a  reac- 
tion increases  rapidly  with  rise  of  temperature,  in  the  case  of 
ferments  this  increase  occm's  only  up  to  a  certain  point.  This  point 
is  spoken  of  as  the  optimum  temperature  of  the  ferment  action.  If  the 
mixture  be  heated  above  this  point  the  action  of  the  ferment  rapidly 
slows  off  and  then  ceases.  This  contrast,  again,  is  only  apparent. 
The  ferments  are  unstable  bodies  easily  altered  by  change  in  their 
physical  conditions,  and  destroyed  in  all  cases  at  a  temperature  con- 
siderably below  that  of  boiling  water.  Thus  ferment  actions,  like  cata- 
lytic actions,  are  quickened  by  rise  of  temperature,  but  the  effect  of 
temperature  is  finally  put  a  stop  to  by  the  destruction  of  the  ferment. 
The  same  applies  to  these  inorganic  catalysers  whose  physical  state  is 
susceptible,  like  that  of  the  ferments,  to  the  action  of  heat.  Thus  the 
colloidal  platinum  '  sol '  exerts  marked  catalytic  effects  on  various 
reactions,  e.g.  on  the  decomposition  of  hydrogen  peroxide  and  on  the 
combination  of  hydrogen  and  oxygen.  The  reaction  presents  an  optimum 
temperature,  owing  to  the  fact  that  the  colloidal  platinum  is  altered, 
coagulated,  and  thrown  out  of  solution  when  this  is  heated  to  near 
boiling-point.  We  may  therefore  employ  either  class  of  reactions  in 
trying  to  form  some  conception  of  the  processes  which  are  actually 
involved. 

Very  many  theories  have  been  put  forward  to  account  for  this 
action  of  catalysers  or  of  ferments.  Many  of  them  are  merely  tran- 
scriptions in  words  of  the  processes  which  actually  occur,  and  fail 
to  throw  any  light  on  their  real  nature.  The  essential  phenomena 
involved  fall  directly  into  two  classes.  In  the  fijst  class  we  must 
place  those  which  are  determined  by  the  influence  of  surface.    In 


CHEMICAL  CHANGES  IN  LIVING  MATTER.   FERMENTS   179 

many  cases  the  combination  of  gases  can  be  hastened  by  increasing 
the  surface  to  which  they  are  exposed,  as  by  passing  them  over  broken 
porcelain  or  over  powdered  charcoal.  This  catalytic  effect  is  certainly 
connected  with  the  power  of  a  sohd  to  condense  gases  at  its 
smiace,  and  is  therefore  proportional  to  the  extent  of  smiace  exposed. 
Thus  the  efficacy  of  platinum  in  hastening  the  combination  of 
hydrogen  and  oxygen  is  in  direct  proportion  to  its  fineness  of  sub- 
division, and  is  best  marked  when  the  metal  is  reduced  to  ultra- 
microscopic  dimensions,  as  in  the  colloidal  solution  of  platinum. 
Every  colloidal  solution  must  be  regarded  as  presenting  an  enormous 
surface  in  proportion  to  the  mass  of  substance  in  solution.  There  is 
therefore  a  direct  proportionahty  between  the  power  of  a  substance 
to  condense  a  gas  on  its  surface  and  its  power  to  quicken  the  velocity 
of  chemical  changes  in  which  the  gas  is  involved.  The  same  process  of 
condensation  occurs  with  dissolved  substances.  Just  as  the  pressure 
of  a  gas  in  immediate  contact  with  a  solid  body  is  diminished,  so  the 
osmotic  pressure  of  a  substance  in  solution  is  diminished  at  the  surface. 
There  is  therefore  a  diffusion  of  dissolved  substances  into  the  surface, 
i.e.  a  concentration  of  dissolved  substances  at  the  surface  of  contact. 
It  was  suggested  by  Faraday  that  the  catalytic  property  of  surfaces 
was  due  to  this  condensation  of  molecules,  and  the  consequent  bringing 
of  the  two  sets  of  molecules  wathin  each  other's  sphere  of  influence. 
Whether  this  is  the  sole  factor  involved  is  doubtful,  since  mere  com- 
pression of  gases  or  increased  concentration  of  solutions  does  not  in 
the  majority  of  cases  result  in  such  a  quickening  of  the  velocity  of 
reaction  as  is  brought  about  by  the  effect  of  the  surface. 

It  is  possible  that  this  condensation  effect  or  adsorption  may  be 
in  every  case  combined  with  the  second  factor  which  we  must  now 
consider,  namely,  the  formation  of  intermediate  products.  If  we 
boil  an  alkaline  solution  of  indigo  with  some  glucose,  the  indigo  is 
reduced  with  oxidation  of  the  glucose.  The  mixture  therefore  becomes 
colourless.  On  shaking  up  with  air  the  colourless  reduction  product 
of  the  indigo  absorbs  oxygen  from  the  atmosphere,  and  is  re-trans- 
formed into  indigo.  These  two  processes  can  be  repeated  until  the 
whole  of  the  glucose  is  oxidised,  and  the  process  can  be  made  continuous 
if  air  or  oxygen  be  bubbled  through  a  heated  solution  of  glucose  contain- 
ing a  small  trace  of  indigo.  In  this  case  the  indigo  does  not  add  to  the 
energy  of  the  reaction.  It  appears  unchanged  among  the  final  products 
and  a  small  amount  may  be  used  to  effect  the  change  of  an  infinite 
quantity  of  glucose.  It  therefore  may  be  said  to  act  as  a  ferment  or 
catalytic  agent.  Instead  of  an  alkaline  solution  of  indigo,  we  may 
use  an  ammoniacal  solution  of  cupric  oxide  for  the  purpose  of  carrying 
oxygen  from  the  atmosphere  to  the  glucose.  This  is  reduced  to  cuprous 
hydrate  on  heating  with  the  sugar,  but  cupric  hydrate  can  be  at  once 


180  PHYSIOLOGY 

re-formed  by  shaking  up  the  cuprous  solution  with  air.  It  has  been 
thought  that  many  or  all  of  the  catalytic  reactions  occur  in  the  same 
way  by  two  stages,  i.e.  by  the  formation  of  an  intermediate  product. 
Thus,  in  the  ordinary  process  for  the  manufacture  of  sulphuric  acid, 
the  nitric  oxide  may  be  supposed  to  combine  with  the  oxygen  of  the 
air  to  form  nitrogen  peroxide.  This  interacts  with  sulphur  dioxide, 
giving  sulphur  trioxide  and  nitric  oxide  once  more.  The  nitric  oxide, 
which  we  alluded  to  before  as  the  catalyser,  may  in  this  way  be  regarded 
as  the  carrier  of  oxygen  from  air  to  sulphur  dioxide.  It  has  been 
suggested  that  the  action  of  spongy  platinum  or  colloidal  platinum 
rests  on  the  same  process,  and  that  in  the  oxidation  of  hydrogen,  for 
instance,  PtO  or  PtOa  is  formed  and  at  once  reduced  by  the  hydrogen 
with  the  formation  of  water. 

There  is  a  certain  amount  of  experimental  evidence  in  favour  of  this  hypo- 
thesis. According  to  Engler  and  Wohler,*  platinum  black,  which  has  been 
exposed  to  oxygen,  in  virtue  of  the  gas  which  it  has  occluded,  has  the  power 
of  turning  potassium  iodide  and  starch  blue.  This  power  is  not  destroyed 
by  heating  to  260°  in  an  atmosphere  of  CO2,  or  by  washing  with  hot  water. 
On  exposure  of  the  platinum  black  to  hydrochloric  acid,  a  certain  amomit  is 
dissolved,  and  the  substance  loses  its  effect  on  potassium  iodide.  The  amount 
dissolved  corresponds  with  the  amount  of  iodine  liberated  from  potassium 
iodide,  and  also  -with  the  amoiuit  of  oxygen  occluded,  the  (soluble)  platinum 
and  oxygen  being  in  the  proportions  necessary  to  form  the  compound  PtO. 

But  why  should  a  reaction  take  place  more  quickly  if  it  occurs 
in  two  stages  instead  of  one  ?  As  Ostwald  has  pointed  out,  the 
formation  of  an  intermediate  compound  can  be  regarded  as  a  suffi- 
cient explanation  of  a  catalytic  process  only  when  it  can  be  demon- 
strated by  actual  experiment  that  the  rapidity  of  formation  of  the 
intermediate  compound  and  the  rapidity  of  its  decomposition  into 
the  end-products  of  the  reaction  are  in  sum  greater  than  the  velocity 
of  the  reaction  without  the  formation  of  the  intermediate  body.  In 
the  case  of  one  reaction  this  requirement  has  been  fulfilled.  The 
catalytic  effect  of  molybdic  acid  on  the  interaction  of  hydriodic  acid 
and  hydrogen  peroxide  has  been  explained  by  assuming  that  the 
first  action  which  takes  place  is  the  formation  of  permolybdic  acid, 
and  that  this  then  interacts  with  the  hydrogen  iodide  to  form  water 
and  iodine.  Now  it  has  been  actually  shown — (1)  that  permolybdic 
acid  is  formed  by  the  action  of  hydrogen  peroxide  on  molybdic  acid  ; 
(2)  that  permolybdic  acid  with  hydriodic  acid  produces  water  and 
iodine ;  (3)  that  the  velocity  with  which  these  two  reactions  occur 
is  much  greater  than  the  velocity  of  the  interaction  of  hydrogen  per- 
oxide and  hydriodic  acid  by  themselves. 

Although  we  may  find  it  difficult  to  explain  why  a  reaction  should  occur 
more  quickly  in  the  presence  of  a  catalyser  by  the  formation  of  these  inter- 

*  Quoted  by  Mellor,  "  Chemical  Statics." 


CHEMICAL  riHANGES  IN  LIVING  MATTER.   FERMENTS    181 

mediate  bodies,  certain  simple  analogies  may  help  us  to  comprehend  how  a 
factor  which  introduces  no  energy  can  yet  assist  the  process.  Thus  a  man 
might  stand  to  all  eternity  before  a  perpendicular  wall  twenty  feet  high.  Since 
he  cannot  reach  its  top  at  one  jump,  he  is  unable  to  get  there  at  all.  "J'he  intro- 
duction of  a  ladder  will  not  in  any  way  alter  the  total  energy  he  must  ex[x;nd 
on  raising  his  body  for  twentj^  feet,  but  will  enable  him  to  attain  the  top.  Or 
we  might  imagine  a  stone  perched  at  the  top  of  a  high  hill.  The  passive 
resistanceof  the  system,  the  friction  of  the  stone,  and  its  inertia  will  tend  to  keep 
it  at  rest,  even  tliough  it  be  on  a  sloping  surface  and  tlicrefore  tending  to  slide 
or  roll  to  tlie  bottom.  If,  liowevcr,  it  be  rolled  to  the  edge,  to  a  point  where 
there  is  a  sudden  increase  in  the  rapidity  of  slope,  it  may  roll  over,  and  having 
once  started  its  downward  course,  its  momentum  will  carry  it  to  the  bottom. 
The  amount  of  energy  set  free  by  the  stone  in  its  fall  will  not  vary  whether 
the  course  be  a  uniform  one,  or  whether  it  falls  over  a  precipice  at  one 
time  and  rolls  down  a  gentle  slope  at  another.  It  is  evident  that  by 
a  mere  alteration  of  the  slope,  or,  in  the  case  of  a  chemical  reaction,  of  the 
velocity  of  part  of  its  course,  a  change  in  the  system  may  be  initiated  and  brought 
to  a  conclusion  wliich  without  this  alteration  ^^•ould  never  take  place. 

Since  the  action  of  ferments,  like  that  of  catalysts,  consists 
essentially  in  tlie  quickening  up  of  processes  which  would  otherwise 
occur  at  an  infinitely  slow  velocity,  it  is  possible  that  in  their  case  also 
the  formation  of  an  intermediate  compound  may  be  involved  in  the 
reaction.  Light  may  be  tlirown  upon  this  question  by  a  study  of  the 
velocity  of  the  reaction  induced  by  the  action  of  a  ferment. 

It  is  well  knoA\ii  that  the  velocity  of  a  reaction  depends  on  the  number 
of  molecules  involved.  As  an  illustration,  we  maj'  take  first  the  case  of  a 
reaction  involving  a  change  in  one  substance.  If  arseniuretted  hydrogen  be 
heated,  it  undergoes  decomposition  into  hydrogen  and  arsenic.  This  decom- 
position is  not  immediate,  but  takes  a  certain  time,  and  the  velocity  with  wliich 
the  change  occxxrs  depends  on  the  temperature.  At  any  given  temperature 
tlie  amount  of  substance  changed  in  the  unit  of  time  varies  with  the  concentra- 
tion of  the  substance.  If,  for  instance,  one-tenth  of  the  gas  be  dissociated 
in  the  first  minute,  in  the  second  minute  a  further  tenth  of  the  gas  will  also 
be  dissociated.  Thus,  if  we  start  -s^ath  1000  grammes  of  substance,  at  the  enil 
of  the  first  minute  100  grammes  will  have  been  dissociated,  and  900  of  the 
original  substance  will  be  left.  In  the  second  minute  one-tenth  again  of  the 
remaining  substance  will  be  dissociated,  i.e.  90  grammes,  leaving  810  grammes. 
In  the  third  minute  81  grammes  will  be  dissociated,  leaving  729  grammes. 
The  anioimt  changed  in  the  unit  of  time  will  always  bear  the  same  ratio  to 
the  whole  substance  which  is  to  be  changed,  and  will  therefore  be  a  fimction  of 
the  concentration  of  this  substance.  Put  in  the  form  of  an  equation,  we  may 
say  that  (/>,  the  anioimt  changed  in  the  unit  of  time,  will  be  equal  to  KC,  where 
K  is  a  constant  varjang  vnth.  the  substance  in  question  and  with  the  tempera- 
ture, and  C  represents  the  concentration  of  the  substance.  The  equation  <p  =  KC 
applies  to  a  monomolecular  reaction. 

If  two  substances  are  involved,  the  equation  \\\\\  be  rather  different. 
In  this  case  the  amount  of  change  in  a  unit  of  time  will  be  a  function  of  the 
concentration  of  each  of  the  substances,  and  the  form  of  the  equation  will  be 
(j,  =  K(C<  X  Cy),  In  the  case  of  the  imimolecular  reaction,  hahing  the  con- 
centration of  the  substance  will  halve  the  amount  of  substance  changed  in 
the  unit  of  time.     In  the  case  of  a  bimolccular  reaction,  halving  each  of  the 


182  PHYSIOLOGY 

substances  will  cause  the  amount  of  change  in  the  unit  of  time  to  be  reduced 
to  one-quarter  of  its  previous  amount.  If  now  either  a  unimolecular  or  a 
bimolecular  reaction  be  quickened  by  the  addition  of  a  catalyser  or  ferment, 
and  the  ferment  enter  into  combination  with  one  of  the  substances  at  some 
stage  of  the  reaction,  it  is  evident  that  our  equation  must  take  account  also 
of  the  concentration  of  the  ferment  or  catalyser.  In  the  case  of  the  catalytic 
effect  of  molybdic  acid  on  the  interaction  between  hydrogen  peroxide  and  HI, 
there  was  definite  evidence  of  a  reaction  taking  place  between  the  molybdic 
acid  and  the  peroxide,  resulting  in  the  formation  of  an  intermediate  compound, 
namely,  permolybdic  acid.  Erode  has  sho^^Ti  that  the  interaction  of  the  molybdic 
acid  is  revealed  in  the  equation  representing  the  velocity  of  the  reaction. 
Without  the  addition  of  molybdic  acid  the  equation  would  be  : 

.?,=K(Ch,o,  xChi). 

After  the  addition  of  molybdic  acid,  the  equation  becomes  : 

(p  =  K(Ch,o,  +  7  C  molybdic  acid)CHi, 

when  y  is  another  constant  depending  on  the  molybdic  acid.  If  fermenis 
act  in  a  similar  way  by  the  formation  of  intermediate  compounds,  this  fact 
should  be  revealed  by  a  study  of  the  velocity  at  which  the  ferment  action  takes 
place. 

Various  methods  may  be  adopted  for  the  study  of  the  velocity  of 
ferment  in  action.  If  for  instance,  we  are  investigating  the  action 
of  diastase  upon  starch,  we  should  take  solutions  of  starch  and  of 
diastase  of  known  concentrations,  keep  them  in  a  water  bath  at 
38°  C,  and  at  a  certain  point  add,  say,  20  c.c.  of  ferment  solution  to 
every  100  c.c.  of  the  starch  solution.  At  periods  of  five  or  ten  minutes 
after  the  addition  had  been  made,  5  c.c.  of  the  mixture  might  be  with- 
drawn by  a  pipette  and  at  once  run  into  boiling  FehUng's  solution. 
The  precipitated  cuprous  oxide  would  be  dried  and  weighed,  and 
would  give  directly  the  amount  of  sugar  formed  by  the  action  of  the 
ferment.  After  obtaining  a  series  of  data  in  this  way,  a  curve  could 
be  drawn,  showing  the  amount  of  change  of  starch  which  had  occurred 
in  each  unit  of  time.  In  the  case  of  the  action  of  invertase  on  cane 
sugar  the  investigation  is  still  easier.  Since  the  change  from  cane 
sugar  to  invert  sugar  is  accompanied  by  a  change  in  the  rotatory 
power  of  the  solution  on  polarised  light,  it  is  onlv  necessary  to  put 
the  mixture  of  ferment  and  cane  sugar  into  a  polarimeter  tube,  which 
IS  kept  at  a  constant  temperature  by  means  of  a  water  jacket,  and 
read  off  at  intervals  of  a  few  minutes  the  change  in  the  rotatory  power 
of  the  solution.  From  this  change  can  be  easily  calculated  the  per- 
centage of  cane  sugar  still  present,  and  therefore  the  total  amount 
which  has  been  converted  into  fructose  and  glucose. 

In*  investigating  the  action  of  proteolvtic  ferments,  as,  e.g.  that 
of  trypsin  on  caseinogen,  samples  are  taken  at  five-minute  intervals 
and  run  into  some  substance  such  as  trichloracetic  acid,  which  will 
precipitate  all  the  unchanged  protein,  but  will  leave  in  solution  the 
products  of  hydration  of  the  protein.     From  the  amount  of  nitrogen 


CHEMICAL  CHANGES  IN  LIVING  MATTER.   FERMENTS     183 

in  the  filtrate  from  the  precipitate  can  be  determined  the  total  amount 
of  protein  which  has  undergone  hydration  in  the  sample  under  observa- 
tion. Or  the  amount  of  albumoses  and  peptones  present  in  each  sample 
may  be  estimated  by  the  intensity  of  the  biuret  reaction  which  can 
be  obtained.  This  method,  however,  suffers  from  the  drawback  that 
the  albumoses  and  peptones,  at  any  rate  in  the  action  of  trypsin,  are 
formed  merely  as  a  stage  in  the  process,  and  the  intensity  of  the 
reaction  will  first  rise  to  a  maximum  and  then  gradually  disappear. 
A  very  convenient  method  is  that  employed  by  Henri  and  by  Bayliss 
in  the  investigation  of  the  kinetics  of  tryptic  action,  namely,  the 
determination  of  the  conductivity  of  the  solution.  In  the  disintegra- 
tion of  the  molecule  caused  by  the  action  of  the  ferment,  there  is  a 
continuous  increase  in  the  conductivity  of  the  solution,  and  this  increase 
can  be  regarded  as  an  index  to  the  rate  of  change  in  the  substances 
undergoing  disintegration. 

By  such  methods  it  has  been  found  that,  when  the  quantity  of 
ferment  employed  is  very  small  in  comparison  with  the  substrate 
(the  substance  acted  upon),  the  amount  of  change  in  a  given  time  is 
proportional  to  the  amount  of  ferment  present,  and  is  (within  hmits) 
independent  of  the  concentration  of  the  substrate.  This  is  well 
shown  by  the  two  following  Tables  representing  the  action  of  lactase 
upon  lactose  (E.  F.  Armstrong) : 


Proportions 

Hydrolysed  ry  100  c.c.  of  a  5  per  cest. 
Solution  of  Lactose 

Solutions  containing — 

15  hours 

20  hours 

45  hours 

1  c.c.  lactase 

015 

o.o 

3-9 

10  c.c.      „ 

. 

IG 

23-3 

38-6 

2(»  cc.        ., 

3-2 

45-S 

— 

Amovnt  of  Sugar  (Lactose)  Hydrolysed 


Solutions  containing — 

24  hours 

46  1 

ours 

Proportion 

Weight 

Proportion 

Weight 

10  per  cent,  lactose 

14-2 

1-42 

22-2 

o.oo 

20       ., 

7-0 

1-40 

ion 

218 

30       „ 

4-8 

1-44 

7-7 

2-21 

184 


PHYSIOLOGY 


Moreover,  if  we  take  only  the  earlier  stages  of  the  ferment  action,  it 
is  found  that,  with  small  proportions  of  ferment,  equal  amounts  of 
substrate  are  changed  in  successive  intervals  of  time  until  about 
10  per  cent,  has  been  hydrolysed.  This  is  shown  in  the  following 
Table  : 


Time 


3        >» 

1  „ 

2  hours 

3  „ 


2  PER  CENT.  Lactose  with  Lactase 

Amount  hydrolj'sed 

3-2 

6-4 

9-6 

.      16-4 

.      20-8 


These  results  can  be  interpreted  only  by  assuming  that  the  first  stage 
in  the  reaction  is  a  combination  of  ferment  with  substrate.  It  is  only 
this  compound  which  represents  the  active  mass  of  the  molecules, 
i.e.  the  molecules  of  substrate  which  are  undergoing  change.  This 
compound,  as  soon  as  it  is  formed,  takes  up  water  and  breaks  down, 
setting  free  the  hydrolysed  substrate  and  the  ferment,  which  is  at 
once  ready  to  combine  with  a  further  portion  of  the  substrate.  In 
such  a  case  the  velocity  of  reaction  must  be  directly  proportional  to 
the  amount  of  ferment,  and  the  same  absolute  quantity  of  substance 
will  continue  to  be  changed  in  succeeding  units  of  time.  Supposing, 
for  instance,  we  had  a  load  of  bricks  at  the  bottom  of  a  hill  which 
had  to  be  transferred  to  the  top,  and  five  men  to  effect  the  trans- 
ference. The  rate  of  transference  would  be  directly  proportional  to 
the  number  of  men  employed  ;  we  could  double  the  rate  by  doubling 
the  men.  Moreover,  the  number  of  bricks  carried  in  each  imit  of 
time  would  be  the  same.  Five  men  would  carry  as  many  bricks  in 
the  second  ten  minutes  as  they  would  in  the  first,  and  so  on.  On  the 
other  hand,  the  velocity  with  which  the  transference  was  effected  would 
be  independent  of  the  number — that  is,  the  concentration — of  the  bricks 
at  the  bottom  of  the  hill.  The  active  mass  of  bricks  could  be  regarded 
as  that  number  carried  at  any  moment  by  the  transferring  factor, 
namely,  the  men.  The  equation  of  change  would  be  ^  =  KC,  where 
C  is  the  concentration  of  the  ferment.  This  concentration  is  always 
being  renewed,  and  kept  constant  by  the  breaking  down  of  the  inter- 
mediate product,  so  that  the  rate  of  change  would  be  continuous 
throughout  the  experiment. 

On  the  other  hand,  when  the  amount  of  ferment  is  relatively  large, 
the  rate  of  change,  though  at  first  very  rapid,  tends  continuously  to 
diminish.  This  is  shown  by  the  following  Table  representing  the  rates 
of  change,  during  succeeding  intervals  of  ten  minutes,  in  a  caseinogen 
solution  to  which  a  strong  solution  of  trypsin  had  been  added 
(Bayliss)  : 


CHEMIC!AL  CHANGES  [N  LIVING  MATTKR.    FERMKNTS    185 

Velocity  of  Tryi-sin  Reaction 


10 

trypsin  ;it  39°  C. 


(j  c.c.  8  per  cent,  cascinogen  +  2  c.c.  —  AmHO  +  2  c.c.  2  per  cent. 


1st  10  iniiiutos 

2nd 

3rd 

4th 

5th 

7th 


K  =,0-(K>79 
*0()040 
()(K)32 
00022 
0fK)lfi 
0-0009 


&c.  &c. 

The  cause  of  this  rapid  diiniimtioii  in  tlie  velocity  of  change  is 
probably  complex.  One  factor  may  be  an  auto- destruction  of  the 
ferment,  which  is  known  to  occur  in  watery  solution.  That  this 
is  not  the  only,  or  even  the  chief,  factor  involved  is  shown  by  the 
fact  that,  when  the  action  of  trypsin  on  caseinogen  has  apparently 
come  to  an  end,  it  may  be  renewed  by  further  dilution  of  the  mixtme 
or  by  removal  of  the  end-products  of  the  action  by  dialysis.  It  is 
evident  that,  in  this  retardation  of  the  later  stages  of  ferment  action, 
the  end-products  are  concerned  in  some  way  or  other,  and  the  retarda- 
tion can  be  augmented  by  adding  to  the  digesting  mixture  the  boiled 
end-products  of  a  previous  digestion.  The  retarding  effect  of  the 
end-products  resembles  in  many  ways  that  observed  in  a  whole  series 
of  reactions  which  are  known  as  reversible. 

As  an  example  of  such  a  reaction  we  may  take  the  case  of  methyl  acetate 
and  water.  When  methyl  acetate  is  mixed  with  water,  it  undergoes  decom- 
position wath  the  formation  of  methyl  alcohol  and  acetic  acid.  On  the  other 
hand,  if  acetic  acid  be  mixed  with  alcohol,  an  interaction  takes  place  with  the 
formation  of  methyl  acetate  and  Avater.  These  changes  are  represented  by  the 
equation : 

MeCaHgOo  +  HOH  =  MeOH  +   HC2H3O2. 

methylacctatc     water    methylalcohol  acetic  acid 

Each  of  these  changes  his  a  certain  velocity  constant,  and,  since  they  are  in 
opposite  directions,  there  must  be  some  equilibrium  point  where  no  change  will 
occur,  and  there  will  be  a  definite  amoimt  of  all  foiu*  substances  present  in  the 
mixture,  namely,  Avater,  alcohol,  ester,  and  acid.  This  equilibrium  point  can 
be  shifted  by  altering  the  amount  of  any  of  the  four  substances'.  Thus  the  inter- 
action of  methyl  acetate  and  water  can  be  diminished  to  any  desired  extent 
by  adding  to  the  mixtiu-o  the  products  of  the  interaction,  namely,  methyl  alcohol 
and  acetic  acid. 

There  is  evidence  that  some  of  the  ferment  actions  are  reversible. 
Thus  maltase  acts  on  maltose  with  the  formation  of  two  molecules  of 
glucose.  If  the  maltase  be  added  to  a  concentrated  solution  of  glucose, 
we  get  a  reverse  effect,  with  the  production  of  a  disaccharide  wliich 
has  been  designated  as  isomaltose  or  revertose.  To  this  reverse  action 
may  be  due  a  certain  amount  of  the  retardation  observed  in  the  action 


180  PHYSIOLOGY 

of  trypsin  on  coagiilable  protein.  A  more  important  factor  is  probably 
the  combination  of  the  ferment  itself  with  the  end-products  and  the 
consequent  removal  of  the  ferment  from  the  sphere  of  action.  Several 
facts  speak  for  such  a  mode  of  explanation.  Thus  the  action  of  lactase 
on  milk  sugar  is  not  retarded  by  both  its  end-products,  namely,  glucose 
and  galactose,  but  only  by  galactose.  In  the  same  way  the  action  of 
invertase  on  cane  sugar  is  retarded  by  the  end-product  fructose,  but 
not  at  all  by  the  other  end-product,  glucose. 

So  far,  therefore,  a  study  of  the  velocity  of  ferment  actions  would 
lead  us  to  suspect  that  the  ferment  combines  in  the  first  place  ^vith  the 
substrate,  and  that  this  combination  is  a  necessary  step  in  the  altera- 
tion of  the  substrate.  In  the  second  place,  the  ferment  is  taken  up 
to  a  certain  extent  by  some  or  all  of  the  end-products,  and  this 
combination  acts  in  opposition  to  the  first  combination,  tending  to 
remove  the  ferment  from  the  sphere  of  action,  and  therefore  to  retard 
the  whole  reaction.  Other  facts  can  be  adduced  in  favour  of  these 
conclusions.  Thus  it  has  been  shown  that  invertase  ferment,  which 
is  destroyed  when  heated  in  watery  solution  at  a  temperature  of  60°  C, 
can,  if  a  large  excess  of  its  substrate,  cane  sugar,  be  present,  be  heated 
25°  higher  without  undergoing  destruction.  The  same  protective 
effect  is  observed  in  the  case  of  trypsin.  Trypsin  in  watery  or  weakly 
alkaline  solutions  undergoes  rapid  decomposition.  At  37°  C.  it  may 
lose  50  per  cent,  of  its  proteolytic  power  within  half  an  hour.  If,  on 
the  other  hand,  trypsin  be  mixed  with  a  protein  such  as  egg  albumin 
or  caseinogen,  or  with  the  products  of  its  own  action,  namely,  albumoses 
and  peptones,  it  can  be  kept  many  hours  without  undergoing  any 
considerable  loss  of  power. 

It  has  been  found  that,  whereas  maltase  splits  up  all  the  «-glucosides, 
it  has  no  power  on  the  /j-glucosides ;  that  is  to  say,  maltai-e  will  fit 
into  a  molecule  of  a  certain  configuration,  but  is  powerless  to  affect  a  mole- 
cule which  differs  from  the  first  only  in  its  stereochemical  structure.  On  the 
other  hand,  emulsin,  which  breaks  up  />glucosides,  has  no  influence  on  o-gluco- 
sides.  This  specific  affinity  of  the  ferments  for  optically  active  groups  of 
bodies  suggests  that  the  ferment  itself  may  be  optically  active.  We  cannot 
of  coiu-se  isolate  the  ferment  and  determine  its  optical  behaviour  ;  but  that 
it  is  optically  active  is  rendered  probable  both  by  these  results  and  certain 
results  obtained  by  Dakin  on  lipase,  the  fat-splitting  ferment.  Dakin  carried 
out  his  experiments  on  the  esters  of  mandehc  acid.  Mandelic  acid  is  optically 
inactive,  but  this  optically  inactive  modification  consists  of  a  mixture  of  equal 
parts  of  dextro-rotatory  and  Isevo-rotatory  mandelic  acid.  The  esters  prepared 
from  the  optically  inactive  acids  are  themselves  optically  inactive.  Dakin 
found  that,  when  an  optically  inactive  mandelic  ester  was  acted  upon  by  a 
lipase  prepared  from  the  liver,  the  final  results  of  the  action  were  also  inactive  ; 
but  if  the  reaction  were  interrupted  at  the  half-way  point,  the  mandelic  acid 
which  had  been  liberated  was  dextro-rotatory,  while  the  remainder  of  the  ester 
was  Isevo-rotatory.  Thus  the  rate  of  hydrolysis  of  the  dextro-component  of 
the  ester  is  greater  than  that  of  the  laevo-componcnt,  a  result  which  can  be 


CHEMICAL  CHANGES  IN  LIVING  MATTER.   FERMENTS    187 

best  explained  by  the  assumptions  (a)  that  the  enzyme  or  a  substance  closely 
associated  with  it  is  a  powerfully  optically  active  substance  ;  (b)  that  actual 
combination  takes  place  between  the  enzyme  and  the  ester  undergoing  hydro- 
lysis. Since  the  additive  compounds  thus  formed  in  the  case  of  the  dextro- 
and  laevo-components  of  the  ester  woidd  not  be  optical  opposites,  they  would 
be  decomposed  -with  unequal  velocity,  and  thus  account  for  the  liberation  of 
the  optically  active  mandelic  acid. 

We  may  conclude  that  in  the  action  of  ferments  on  the  food  sub- 
stances, whether  carbohydrate  or  protein,  an  essential  factor  is  the 
combination  of  the  ferment  \nth  the  substrate.  Only  the  part  of  the 
substrate,  which  is  thus  combined  ^vith  the  ferment,  can  be  regarded 
as  the  active  mass  and  as  undergoing  the  hydrolytic  change.  "What 
is  the  nature  of  this  combination  ?  Ferments,  which  are  all  of  a 
colloid  or  semi-colloid  character,  cannot  be  dealt  with  in  the  same  way 
as  the  catalysts  of  definite  chemical  composition,  such  as  molybdic 
acid  or  nitric  oxide.  In  many  cases  the  substrate,  e.g.  starch  or 
protein,  is  also  colloidal,  and  the  combination  therefore  falls  into  the 
class  of  combinations  between  colloids.  In  this  we  have  an  inter- 
action between  two  substances  in  which  the  adsorption  by  the  sur- 
faces of  the  molecules  of  one  or  both  substances  plays  an  important 
part,  though  this  adsorption  is  itself  determined  or  modified  by  the 
chemical  configuration  of  the  molecules.  The  combination  of  ferments 
\vith  their  substrates  belongs,  therefore,  to  that  special  class  of  inter- 
actions, not  entirely  chemical  and  not  entirely  physical,  but  depending 
for  their  existence  on  a  co-operation  of  both  chemical  and  physical 
factors,  which  we  have  discussed  earlier  under  the  name  of  adsorption 
compounds. 

FERMENTS    AS    SYNTHETIC    AGENTS 

If  maltase,  obtained  from  yeast,  or  from  the  so-called  takadiastase 
(prepared  from  Aspergillus  oryzoe),  be  added  to  a  solution  of  maltose, 
the  latter  is  bydrolvsed  to  glucose.  The  process  of  hydrolysis 
stops  short  of  complete  inversion  at  a  point  varying  with  the 
concentration  of  the  sugar  solution.  Thus  in  a  10  per  cent,  solution 
of  maltose,  inversion  proceeds  until  98  per  cent,  of  the  maltose  is 
converted  into  dextrose,  whereas  in  a  40  per  cent,  solution  the  change 
stops  short  when  85  per  cent,  sugar  has  undergone  inversion.  Croft  Hill 
showed  that  if  the  maltase  were  added  to  a  40  per  cent,  solution  of 
dextrose,  a  change  took  place  in  the  reverse  direction,  which  pro- 
ceeded until  85  per  cent,  of  the  glucose  was  left.  The  sugar  formed, 
which  is  a  disaccharide,  was  regarded  by  Croft  Hill  as  maltose. 
According  to  Emraerling,  however,  it  is  the  stereoisomeric  sugar,  iso- 
maltose,  which  is  formed  ;  and  Croft  Hill  in  his  later  papers  spoke  of  the 
sugar  as  revertose. 

In  the  same  way  it  has  been  shown  by  Castle  and  Loewenhart 


188  PHYSIOLOGY 

that  the  hydrolysis  of  esters  by  Hpase  is  a  reversible  reaction,  the 
action  of  lipase  being  simply  to  hasten  the  attainment  of  the  equili- 
brium point  between  the  four  substances — ester  (or  neutral  fat),  water, 
fatty  acid,  and  alcohol.  Similar  reversible  effects  have  been  described 
for  other  ferments.  Thus  the  addition  of  pepsin  to  a  strong  solution 
of  albumoses  causes  the  appearance  of  an  insoluble  precipitate,  which 
is  called  flastein,  and  has  been  regarded  as  produced  by  the  resynthesis 
of  the  original  protein  molecule. 

If  all  ferment  actions  are  in  this  way  reversible,  a  possibility  is 
opened  of  regarding  the  synthetic  processes  occurring  in  the  living 
cell,  as  well  as  the  processes  of  disintegration,  as  determined  by  the 
action  of  enzymes.  It  must  be  noted  that  these  effects  are  only 
obtained  witlx  distinctness  when  dealing  with  concentrated  solutions. 
The  degree  of  synthesis  which  would  be  produced  in  the  very  dilute 
solutions  of  glucose,  &c.,  occurring  in  the  animal  cell  would  therefore 
be  infinitesimal.  But  if  a  mechanism  were  provided  for  the  immediate 
separation  of  the  synthetical  product  from  the  sphere  of  reaction, 
either  by  removing  it  to  a  different  part  of  the  cell  or  by  building  it 
up  into  some  more  complex  body  which  was  not  acted  on  by  the  ferment, 
the  process  of  synthesis  might  go  on  indefinitely,  and  the  infinitesimal 
quantities  be  summated  to  an  appreciable  amount. 

Some  experiments  by  Bertrand  on  fat  synthesis  have  been  inter- 
preted as  showing  that  the  process  of  synthesis  by  ferments  is  not  the 
mere  attainment  of  an  equilibrium  point  in  a  reversible  reaction.  It 
has  long  been  known  that  watery  extracts  of  the  fresh  pancreas  split 
neutral  fats  into  the  higher  fatty  acids  and  glycerine.  This  observer 
has  shown  that  if  the  pancreas  be  dried  with  alcohol  and  ether  and 
powdered,  addition  of  the  dry  powder  to  a  mixture  of  the  higher  fatty 
acids  and  glycerine  brings  about  a  rapid  synthesis  of  neutral  fat.  The 
process  of  synthesis  is  at  once  stopped  by  the  addition  of  water.  In 
this  case  either  there  are  two  ferments  present,  one  a  synthetising,  the 
other  a  hydrolysing,  ferment,  differing  in  their  conditions  of  activity, 
or  there  is  one  ferment  which  may  act  either  as  a  fat-splitting  or  fat- 
forming  agent  according  to  the  conditions  under  which  it  is  placed. 
In  the  latter  case  the  effect  of  the  addition  of  water  would  be  simply 
to  alter  the  equilibrium  point  of  the  mixture.  It  has  been  shown  that 
in  all  reversible  reactions  the  equilibrium  position  is  the  same  from 
whichever  side  it  be  approached.  The  action  of  the  ferment  is  to 
hasten  the  attainment  of  equilibrium,  the  position  of  the  latter  being 
determined  by  the  relative  concentration  of  the  reacting  molecules. 


SECTION  V 

ELECTRICAL  CHANGES   IN   LIVING  TISSUES 

The  material  composing  living  cells  and  tissues  is  permeated 
throughout  with  water  containing  electrolytes  in  solution.  All  salts, 
as  we  have  seen,  undergo  ionic  dissociation  in  watery  solution — a  dis- 
sociation which,  in  the  concentrations  occurring  in  the  animal  body, 
must  be  nearly  complete.  When  an  electric  current  passes  through 
the  living  tissues  it  is  carried  by  the  charged  ions  formed  by  the 

dissociation   of  the  salts.     Thus,   n/10  solution   of  sodium  chloride 

+ 
contains  almost  entirely  Na  and  CI  ions.     In  addition  to  these  charged 

inorganic  ions,  the  cell  protoplasm  contains  in  solution  or  suspension 

various  colloidal  particles  which  in  many  cases  are  themselves  charged. 

By  the  presence  of  these  colloidal  particles  marked  differences  may 

be  caused  in  the  distribution  of  the  inorganic  ions  o^N'ing  to  the  power 

of  adsorption  possessed  by  the  colloids  for  many  inorganic  salts.     It 

is  evident  that  any  unequal  distribution  of  the  charged  ions  or  colloidal 

particles  in  a  tissue  or  on  the  two  sides  of  a  membrane  may  give  rise 

to  corresponding  unequal  distribution  of  electric  charges,  and  therefore 

differences  of  potential  between  different  parts  of  the  tissue,  which 

under  suitable  conditions  may  find  their  expression  in  an   electric 

current.     It  is  therefore  not  surprising  that  practically  every  functional 

change  in  a  tissue  has  been  shown  to  be  associated  with  the  production 

of  differences  of  electrical  potential.     Thus  all  parts  of  an  miinjured 

muscle    are    isopotential,  and  any  two  points  may  be  led  off  to  a 

galvanometer  without  any  current  being  observed.     If,  however,  one 

part  of  the  muscle  be  strongly  excited,  as,  for  instance,  by  injury,  so 

that  it  is  brought  into  a  state  of  lasting  excitation,  it  will  be  found 

that,  on  leading  off  from  this  point  and  a  point  on  the  uninjured  surface 

to  a    galvanometer,    a    current  flows  through    the    latter   from   the 

uninjured  to  the  injured  surface.     Every  beat  of  the  heart,  every 

twitch  of  a  muscle,  every  state  of  secretion  of  a  gland,  is  associated 

in  the  same  way  with  electrical  changes.     In  most  cases  the  electrical 

changes  associated  with  activity  have  the  same  general  character,  tlie 

excited  part  being  found  to  be  negative  in  reference  to  any  other  part 

of  the  tissue  which  is  at  rest.     The  uniform  character  of  the  electric 

response  in  different  kinds  of  tissues  suggests  that  an  accurate  knowledge 

of  the  changes  in  the  distribution  of  charged  ions  responsible  for  the 

189 


190 


PHYSIOLOGY 


response  ought  to  throw  important  light  on  the  intimate  nature  of 
excitation  generally.  It  may  be  therefore  advisable  to  consider  more 
closely  the  conditions  which  determine  differences  of  potential  in  a 
complex  system  of  electrolytes. 

As  a  simple  case  we  may  take  an  ordinary  concentration  cell. 
Two  vessels  (Fig.  29),  A  and  B,  are  united  by  a  glass  tube  C.  A  contains 
a  10  per  cent,  solution  of  zinc  sulphate  and  B  a  1  per  cent,  solution  of 
the  same  salt.  A  rod  of  pure  zinc  is  immersed  in  each  limb.  On 
connecting  the  zinc  by  a  zinc  wire  to  a  galvanometer  a  current  is 
observed  to  flow  from  A  to  B  through  the  galvanometer,  and  therefore 


C 

7n 

®Zn 

- 

©2/7 

Zn© 

- 

©2/7 

2n 

© 
Zn 

u 

©z^ 

®2n 

Fig.  29. 


Fig.  30. 


from  B  to  A  through  the  cell.     A  solution  of  zinc  sulphate  contains 

+  — 

partlv  undissociated  ZnS04  and  partly  dissociated  Zn  and  SO4  ions. 
If  a  rod  of  zinc  be  immersed  in  a  watery  fluid  the  zinc  tends  to  dis- 
solve. The  Zn  passing  into  the  fluid  is,  however,  directly  ionised,  and 
therefore  carries  a  positiv^e  charge  into  the  fluid,  leaving  the  zinc 
negatively  charged  (Eig.  30).  This  process  of  solution  will  rapidly 
come  to  an  end,  since  the  positively  charged  ions  in  the  fluid  will 
repel  back  into  the  zinc  any  ions  which  may  be  escaping  from 
the  zinc.  The  amount  of  zinc  actually  dissolved  in  the  fluid  is 
infinitesimal,  the  process  of  solution  ceasing  when  the  pressure  (osmotic 
pressure)  of  the  Zn  ions  in  the  fluid  equals  what  may  be  called  the 
'  electrolytic  solution  pressure  '  of  the  zinc  .The  continued  solution 
of  the  zinc  is  therefore  only  possible  when  means  are  supplied  for  the 
Zn  ions  in  the  fluid  to  get  rid  of  their  positive  charges. 

In  an  ordinary  Daniell  cell  the  Zn  ions  which  leave  the  zinc  are 
discharged  by  combining  with  the  SO4  ions  passing  to  the  zinc  from 


ELECTRICAL  CHANGES  IN  LIVING  TISSUES  191 

the  copper  sulphate  in  the  outer  cell.  It  is  a  well-known  fact  that 
pure  zinc  does  not  dissolve  in  acid  until  some  other  metal,  such  sm 
copper,  is  brought  into  contact  with  it,  so  as  to  set  up  an  electric 
couple,  i.e.  to  provide  means  for  the  discharge  of  the  Zn  ions  passing 
into  the  solution.  When  the  zinc  is  immersed  in  the  two  solutions 
of  zinc  sulphate  in  the  concentration  battery,  the  same  change  will 
occur.  The  Zn804  solution  in  the  two  Umbs  of  the  concentration 
cell  already  contains  Zn  ions.  Since  their  pressm-e  in  the  10  per  cent, 
solution  is  greater  than  in  the  1  per  cent,  solution,  fewer  Zn  ions  will 
leave  the  zinc  in  A  than  in  B.  The  negative  charge  on  the  Zn  in  A 
will  therefore  be  less  than  that  on  the  rod  in  B,  and  positive  electricity 
will  therefore  flow  from  A  to  B.  This  will  disturb  the  equilibrium 
at  the  surface  both  of  B  and  A,  so  that  Zn  ions  will  be  deposited  from 
the  fluid  on  the  sm'face  of  the  zinc  in  A  and  will  continue  to  pa.ss 
from  zinc  into  solution  in  B.  At  the  same  time  there  is  a  movement 
of  SO4  ions,  set  free  at  the  surface  of  A,  towards  B.  The 
ultimate  result,  therefore,  is  that  the  zinc  in  B  dissolves  and  the  same 
amount  of  zinc  is  deposited  on  A.  The  solution  of  zinc  sulphate 
on  A  becomes  progressively  weaker,  while  that  in  B  becomes  stronger, 
until  finally  the  concentrations  in  the  two  limbs  are  identical  and 
the  current  ceases.  In  this  process  no  chemical  energy  is  involved, 
the  energy  set  free  by  the  conversion  of  zinc  into  zinc  sulphate  in  B 
being  exactly  balanced  by  the  energy  lost  by  the  deposition  of  zinc 
from  zinc  sulphate  in  A.  Yet  the  current  which  is  produced  has  a 
certain  amount  of  energy  which  can  be  utihsed  for  heating  a  wire 
through  which  it  is  made  to  pass.  Since  this  energy  must  be  taken 
from  the  cell,  the  cell  is  cooled  during  the  passage  of  the  current. 
We  have  here  a  close  analogy  with  the  case  of  compressed  gases.  If 
the  10  per  cent,  and  1  per  cent,  solutions  were  mixed  together  in  a 
calorimeter,  no  change  of  temperature  would  be  produced,  since  no 
work  is  done  in  the  process.  In  the  same  way  no  coohng  effect  is 
observed  if  compressed  gas  be  allowed  to  expand  into  a  vacuum.  If, 
however,  the  compressed  gas  be  allowed  to  expand  from  a  narrow 
orifice  against  the  pressure  of  the  external  air,  so  that  it  does  work  in 
the  process,  it  is  cooled,  and  this  coohng  effect  is  made  use  of  in  the 
working  of  refrigerating  machines  or  for  the  liquefaction  of  gases. 
We  may  therefore  regard  the  concentration  battery  as  a  machine  for 
making  the  substances  in  solution  do  work  as  they  expand  from  a 
strong  into  a  dilute  solution. 

The  differences  of  potential  obtained  from  an  ordinary  concentra- 
tion cell  are  very  small  and  would  not  suffice  to  account  for  such  a 
high  electromotive  force  as  is  set  up,  e.g.,  in  the  contraction  of  a 
muscle.  We  have  seen  earher,  however,  that  even  in  isosmotic 
solutions  differences  of  pressure  may  be  brought  about  by  differences 


192 


PHYSIOLOGY 


in  diffusibilitv  of  the  substances  in  solution,  especially  if  the  two 
solutions  be  separated  by  a  membrane.  Very  large  differences  may 
be  produced  if  this  membrane  be  practically  impermeable  to  one  or 
other  of  the  dissolved  substances.  In  the  same  way  a  semipermeable 
membrane,  i.e.  a  membrane  with  different  permeabihties  for  the 
different  ions  of  the  two  solutions,  may  suffice  to  bring  the  differences 
o'  potential  of  a  concentration  cell  up  to  and  beyond  the  extent  which 
is  observed  in  living  tissues.  Supposing  we  have  (Fig.  31)  two  solu- 
tions, A  and  B,  each  containing  an  electrolyte,  UV,  in  different  con- 
centrations separated  by  a  membrane  m.     If  u  represents  the  velocity 

m 


UV 


B 


UV 


Fig.  31. 


of  transmission  of  U  through  m,  and  v  the  velocity  of  V,  then  the 
electromotive  force  of  the  cell  is  given  by  the  formula 


!^  0-0577.  locT.i«-^J  Yo\i. 


If  V  is  taken  as  very  small,  the  membrane  may  be  regarded  as  semi- 
permeable for  the  corresponding  ion  V.  Supposing  we  take  potassium 
chloride  as  the  solution,  we  should  have  to  make  the  concentration  in 
B  eight  times  that  in  A,  in  order  to  get  a  current  of  a  strength  equal 
to  that  obtained  from  the  olfactory  nerve  of  the  pike,  for  example. 
Macdonald  has  made  such  an  assumption  in  order  to  explain  the 
normal  nerve  current.  He  suggests  that  the  axis  cylinder  contains 
an  electrolyte  which  is  equivalent  to  a  2-6  per  cent,  solution  of  potassium 
chloride.  It  is  unnecessary,  however,  to  assume  such  great  differences 
of  concentration  if  we  regard  the  membrane  as  itself  a  solution  of 
electrolytes,  as  has  been  suggested  by  Cremer,  or  if  we  take  different 
substances  on  the  two  sides  of  the  membrane.  In  the  case  of  two 
electrolytes,  UiVj,  U2V2  (U  being  the  cation  in  each  case),  separated 
by  a  membrane  with  varying  permeability  for  the  different  ions,  the 
electromotive  force  of  the  cell  is  given  by  the  following  formula  : 


0-0577  \oo}^ 


«2  +  Vi 


ELECTRICAL  CHANGES  IN  LIVING  TISSUES  I^i3 

where  UiVy,  U2^\,  are  the  velocities  of  the  corresponding  ions.  We 
assume  that  the  concentrations  of  the  two  solutions  are  identical. 
Now  it  is  evident  that  by  making  Wj  and  v^  very  small,  the  expres- 

ni       .  j..    /ij 

sion  log.^°  — may  be  made  to  attain  anv  quantity,  and   in   the 

W2  +  Ui       ' 

same  way  by  making  u^  +  Vg  infinitesimally  small  the  electromotive 

force  of  the  combination  will  also  become  correspondingly  small.    The 

thickness  of  the  membrane  does  not  come  into  the  formula,  so  that 

membranes    of   microscopic  or   even   ultramicroscopic 

thickness,   which   we  have  seen   reason  to  assume  as 

present  in  and  around  cells  and  their    parts,    could 

perform  all  the  functions  required  of  the  hypothetical 

membrane  in  the  above  example.    This  is  also  the  case 

when  Vj  is  the  same  as  V2 — that  is  to  say,  there  is  a 

common  anion  or  a  common  cation  on  the  two  sides 

of  the  membrane. 

It  must  be  remembered  that  the  passage  of  a 
current  through  a  membrane  impermeable  to  one  or 
other  ion  in  the  surrounding  fluid  will  cause  an  accumu- 
lation of  the  ion  at  the  surface  of  the  membrane,  so 
that  this  will  become  polarised.  Such  an  accumu- 
lation at  any  surface  will  naturally  alter  the  properties 
of  the  surface,  including  its  siuiace  tension.  The 
construction  of  the  capillary  electrometer  depends  on 
this  fact.  When  mercury  is  in  contact  with  dilute 
acid  or  mercuric  sulphate  solution  it  takes  a  positive  Fig.  32 
charge  from  the  fluid,  and  the  state  of  stress  at  the 
surface  of  contact  between  the  mercury  and  the  negatively  charged 
fluid  diminishes  the  surface  tension  of  the  mercury.  If  the  mercury 
be  in  the  form  of  a  drop  in  a  tube  diawn  out  to  a  capillary, 
the  merciury  will  run  down  the  capillary  and  the  drop  will  be 
deformed  until  the  surface  tension  tending  to  pull  the  mercury 
into  a  spherical  globule  is  just  equal  to  the  force  of  gravity  tending 
to  make  the  mercury  run  out  through  the  end  of  the  capillarv 
(Fig.  32).  If  the  mercury  be  immersed  in  sulphuric  acid  it  will  descend 
to  a  lower  level  in  the  capillary  owing  to  the  diminution  of  its  surface 
tension.  If  now  the  acid  and  the  mercury  be  connected  with  a  source 
of  current  so  as  to  charge  the  mercury  negatively,  the  effect  will  be 
to  diminish  the  charge  previously  taken  up  by  the  merciu-y.  The 
state  of  tension  at  the  contact  with  the  acid  is  therefore  diminished, 
the  surface  tension  is  increased,  and  the  mercury  withdraws  itself 
from  the  point  of  the  capillary.  If,  however,  the  mercury  be  con- 
nected with  the  positive  pole,  its  charge  will  be  increased  and  its 
surface  tension  correspondingly  diminished,   so   that   the   meniscus 

13 


194  PHYSIOLOGY 

will  move  towards  tlie  point  of  the  capillary.  The  movement  of  the 
meniscus  to  or  away  from  the  point  may  thus  be  used,  as  in  the  capil- 
lary electrometer,  to  show  the  direction  and  amount  of  any  moderate 
electrical  change  occurring  in  a  tissue,  two  points  of  which  are  con- 
nected with  the  mercury  and  the  acid  respectively.  It  is  possible 
that  this  electrical  alteration  of  surface  tension  may  be  a  determining 
factor  in  many  of  the  phenomena  of  movement  observed  in  the  animal 
body.  We  shall  have  occasion  to  discuss  this  question  more  fully 
when  endeavouring  to  account  for  the  ultimate  nature  of  muscular 
contraction. 


BOOK  II 

THE  MECHANISMS  OF  MOVEMENT 
AND  SENSATION 


CHAPTER  V 
THE   CONTRACTILE   TISSUES 

SECTION  1 

THE  STRUCTURE  OF  VOLUNTARY  MUSCLE 

The  most  striking  features  in  the  continual  series  of  adaptations  to 
the  environment,  which  make  up  the  Hfe  of  an  individual,  are  the 
movements  carried  out  by  contractions  of  the  skeletal  muscles.  In 
fact,  all  the  mechanisms  of  nutrition  can  be  regarded  as  directed 
to  the  maintenance  of  the  neuro-muscular  apparatus,  i.e.  of  the 
mechanism  for  adapted  movement.  With  the  growth  of  the  cerebral 
hemispheres,  which  determines  the  rise  in  the  scale  of  animal  life,  the 
skeletal  muscles  become  more  and  more  the  machinery  of  conscious 
reaction.  Even  the  highest  of  the  adaptations  possessed  by  man, 
those  involving  the  use  of  speech,  are  impossible  w^ithout  some  kind 
of  movement.  A  man's  relation  to  his  fellows,  and  his  value  in  the 
community,  are  determined  by  these  higher  muscular  adaptations. 
Tt  is  not,  therefore,  surprising  that  the  organs  of  the  body  which 
present  in  the  highest  degree  the  reactivity  characteristic  of  all  living 
things  should  have  early  attracted  the  attention  of  physiologists  and 
have  been  the  object  of  numberless  researches  directed  to  determining 
the  ultimate  nature  of  the  processes  generally  described  as  vital. 

The  movements  of  the  muscles  are  carried  out  in  response  to 
changes  aroused  in  the  central  nervous  system  by  events  occurring 
in  the  environment  and  acting  on  the  surface  of  the  body.  Every 
movement  of  an  animal  is  thus  in  its  most  primitive  form  a  reflex 
action,  and  involves  changes  in  a  peripheral  sense  organ,  in  an  afferent 
nerve  fibre,  in  the  central  nervous  system,  and  in  an  efferent  nerve 
fibre,  before  the  actual  process  of  contraction  occiu-s  in  the  muscle 
itself  and  gives  rise  to  the  resultant  movement  (Fig.  33).  If  we  are  to 
determine  the  nature  of  the  changes  involved  in  this  reflex  action,  we 
must  be  able  to  study  them  as  they  progi'ess  along  the  different  elements 
which  make  up  the  reflex  arc.  This  analysis  is  facilitated  by  the  fact 
that  we  are  able  to  arouse  a  condition  of  activity  in  the  different 
parts  of  the  arc,  even  when  isolated  from  one  anotlier.  Thus  we  can 
excite  any  given  reflex  movement  by  stimulation  of  the  peripiierv 

197' 


198  PHYSIOLOGY 

of  the  body,  or  of  the  afferent  nerve  passing  from  the  surface  to  the 
central  nervous  system.  We  can  proceed  further  and  cut  the  efferent 
nerve  away  from  the  central  nervous  system  and  still  succeed  in 
exciting  a  condition  of  activity  in  the  efierent  nerve  or  in  its  attached 
muscle.  All  parts  of  the  reflex  arc  possess  the  property  of  excitability, 
and  we  are  thus  able  to  arouse  the  activity  of  each  part  in  turn,  to 
study  its  conditions,  its  time  relations,  and  the  physical  and  chemical 
changes  concomitant  with  the  state  of  activity. 

It  will  be  convenient  for  our  analysis  to  begin  with  the  tissue  whose 
reaction   forms  an   end  link  in  the  reflex  chain,  namelv,  the  muscle, 


Central  Nervous 
'  System 


Sensory  l\|v     Sensory  nerve       9 
Surface  \\  -* 

Fig.  33.     Diagram  of  a  reflex  arc. 

and  to  proceed  from  that  to  the  consideration  of  the  processes  occurring 
in  the  conducting  strand  between  central  nervous  system  and  muscle, 
namely,  the  nerve  fibre,  postponing  to  a  future  chapter  the  treatment 
of  the  more  complex  processes  associated  with  the  central  nervous 
system. 

In  the  higher  animals  we  may  distinguish  several  varieties  of 
muscle.  All  movements  that  require  to  be  sharply  and  forcibly 
carried  out  are  effected  by  means  of  striated  muscular  tissue,  and  as 
these  movements  are  in  nearly  all  cases  under  the  control  of  the  will 
the  muscles  are  generally  spoken  of  as  voluntary.  Unstriated  or 
involuntary  muscles  form  sheets  or  closed  tubes  surrounding  the 
hollow  viscera.  By  their  slow,  prolonged  contractions  they  serve 
to  maintain  and  regulate  the  flow  of  the  contents  of  these  organs. 
Such  fibres  are  found  surrounding  the  blood-vessels,  the  intestine,  the 
ahmentary  canal,  the  bladder,  &c.  Intermediate  in  properties  as 
well  as  structure  between  these  two  classes  is  the  heart  muscle.  This, 
like  voluntary  muscle,  is  striated,  but  presents  considerable  variations 
both  in  structure  and  function  from  ordinary  skeletal  muscle.  Many 
of  its  properties  will  be  considered  in  treating  of  the  physiology  of  the 
heart.  The  properties  of  contractile  tissues  have  been  most  fully 
investigated  in   the  voluntary   muscles,   almost  exclusively  on  the 


THE  STRUCTURE  OF  VOLUNTARY  MUSCLE  199 

muscles  of  cold-blooded  animals,  such  as  the  frog.  The  choice  of 
skeletal  muscles  for  this  purpose  is  justified  by  the  fact  that  a  function 
is  most  easily  investigated  in  the  organs  in  which  it  is  most  highly 
developed.  The  choice  of  cold-blooded  animals  is  guided  by  the 
fact  that  it  is  possible  to  isolate  the  muscle  from  the  rest  of  the  body 
and  to  study  its  reactions  during  a  considerable  time  without  the 
research  being  interfered  with  by  the  death  of  the  tissue.  We  may 
therefore  deal  at  length  with  the  properties  of  the  skeletal  muscles, 
pointing  out  incidentally  in  what  respects  the  heart  muscle  and 
involuntary  muscle  differ  from  the  skeletal  muscle. 

The  voluntary  or  striated  muscles  form  a  large  part  of  the  body, 
and  are  known  as  the  flesh  or  meat.  Each  muscle  is  embedded  in  a 
layer  of  connective  tissue,  and  is  made  up  of  an  aggregation  of  muscular 


Fia.  34.     Muscular  fibre  of  a  mammal,  examined  fresh  iii  scrum, 
highly  magnified.     (Schafer.) 

fibres,  which  are  united  into  bundles  by  means  of  areolar  connective 
tissue.  The  individual  fibres  vary  much  in  length,  and  may  be  as 
long  as  4  or  5  cm.  At  each  end  of  the  muscle  the  fibres  are  firmly 
united  to  tough  bundles  of  white  fibres,  which  form  the  tendon  of 
the  muscle,  and  are  attached  as  a  rule  to  bones.  Running  in  the 
connective  tissue  framework  of  the  muscle  we  find  a  number  of  blood- 
vessels, capillaries  and  nerves. 

On  examination  of  a  living  muscle,  each  fibre  is  seen  to  consist 
of  a  series  of  alternate  Hght  and  dark  striae,  arranged  at  right  angles 
to  its  long  axis,  and  enclosed  in  a  structureless  sheath — the  sarco- 
lemma.  Lying  under  the  sarcolemma  are  a  number  of  oval  nuclei 
embedded  in  a  small  amount  of  granular  protoplasm.  Li  some  animals 
these  nuclei  occupy  a  central  position  in  the  fibre.  Each  band  may 
be  considered  to  be  made  up  of  a  number  of  prisms  (sarcomeres)  side 
by  side,  with  interstitial  substance  (sarcoplasm)  between  them.  The 
muscle  prisms  of  adjacent  discs  are  connected  to  form  long  colunms 
(primitive  fibrillae,  or  sarcostyles).  Each  muscle  prism  is  more  trans- 
parent at  the  two  ends  than  in  the  middle,  thus  giving  rise  to  the 
appearance  of  light  and  dark  stria).  In  the  middle  of  the  light  band 
is  a  fine  or  row  of  dots  (often  appearing  double),  called  Krause  s 
membrane. 


200  .  PHYSIOLOGY 

The  development  of  this  regular  cross  and  longitudinal  striation 
is  closely  connected  with  the  evolution  and  specialisation  of  the 
muscular  function,  i.e.  contraction.  Contractility  is  among  others  a 
function  of  all  midifEerentiated  protoplasm.  Undifferentiated  cells, 
such  as  the  amoeba,   can  effect  only  slow  and  weak  contractions. 


Fig.  36 


Fig.  35 


Fig.    3.5.     Muscle    fibre    of    an    ascaris.     ct,    the   differentiated    eontraetile 

portion  of  tlie  cell.     (After  Hektwig.) 
Fig.  36.     Muscle  fibres  from  the  snuill  intestine,  showing  the  fine  longitudinal 

striation.     (Sohafer.) 

Directly  a  specialisation  of  function  is  necessary  and  some  cell  or 
part  of  a  cell  has  to  contract  rapidly  in  response  to  some  stimulus 
from  within  or  without,  we  find  a  differentiation  both  of  form  and  of 
internal  structure.  In  many  cases,  as  in  the  developing  muscle  of 
the  embryo  or  the  adult  nuiscles  of  many  invertebrates,  this  differentia- 
tion affects  only  part  of  the  cell,  so  that  while  one  part  presents  the 
ordinary  granular  appearance,  the  other  half  is  finely  and  longitu- 


THE  STRUCTURE  OF  VOLUNTARY  MUSCLE  201 

dinally  striated,  the  striation  being  apparently  due  to  the  develop- 
ment of  special  contractile  fibrillae.  In  the  slowly  contracting 
unstriated  muscle  of  the  vertebrate  intestine,  the  longitudinal  striation 
is  with  difficulty  made  out ,  but  as  the  muscle  rises  in  the  scale  of 
efficiency,  the  longitudinal  striation  becomes  more  apparent,  and  in 
the  striated  muscle  of  vertebrates,  and  still  more  in  the  wonderful 
wing-muscles  of  insects,  which  can  perform  three  hundred  complete 
contractions  in  a  second,  the  longitudinal  is  associated  with  and  often 
apparently  subordinated  to  a  transverse  striation,  due  to  the  regular 
segmentation  of  the  contractile  fibrillae  or  sarcostyles.  Every  muscular 
fibre,  which  presents  any  trace  of  histological  differentiation,  may  be 
said  to  consist  of  contractile  fibrillae  (sarcostyles),  each   composed  of 


Fig.  37.  Transverse  sections  of  the  pectoral  muscles  of  a,  the  falcon,  b,  the  goose 
and  c,  the  domestic  fowl.  It  will  be  noticed  that  the  relative  amount  of  granular 
or  red  fibres  present  varies  directly  as  the  bird's  power  of  sustained  flight.  (After 
Knoll.  ) 

a  series  of  contractile  elements  (sarcous  elements  or  sarcomeres), 
and  embedded  in  a  gxanular  material  known  as  sarcoplasm.  The 
great  divergence  in  the  aspect  of  muscular  fibres  from  different 
parts  of  the  animal  kingdom  is  largely  conditioned  by  the  varying 
relations,  spatial  and  quantitative,  of  the  sarcoplasm  to  the  sarco- 
styles. Thus  in  the  higher  vertebrates,  two  types  of  voluntary  muscular 
fibre  are  distinguished,  according  to  the  amount  of  sarcoplasm  they 
contain  :  one  rich  in  sarcoplasm,  more  granular  in  cross-section,  and 
generally  containing  ha^noglobin  ;  and  the  other  poor  in  sarco])lasm, 
clear  in  cross-section,  and  containing  no  haemoglobin.  From  the  fact 
that  the  granular  fibres  are  found  chiefly  in  those  muscles  wliich  have 
to  carry  out  long-continued  and  |)owerful  contractions,  it  seems 
reasonable  to  regard  the  interstitial  sarcoplasm  as  the  local  food- 
supply  of  the  active  sarcostyles,  although  some  authors  have  endowed 
the  sarco])lasm  with  a  contractile  power  of  its  own,  diflfering  only  by 
its  extremely  prolonged  character  from  the  quick  twitch  of  the  sarco- 
styles. The  connection  between  structiu^e  and  activity  of  the  muscle- 
fibres  is  well  shown  by  Fig.  37. 

In  sonic  animals,  such  as  the  rabbit,  we  fuid  nmsclcs  consisting  almost 
entirely  of  one  or  other  of  Ihese  varictios  ;  but  in  lUost  animals  (amongst  wliich 
■we  may  reckon  frog  and  man)  tlie  two  varieties  occur  together  in  one  muscle, 
so  that  what  we  have  to  say  about  the  properties  of  volinitary  muscle,  which 


202 


PHYSIOLOGY 


rests  nearly  entirely  on  experiments  with  frog's  muscle,  really  has  reference  to 
a  mixed  muscle,  i.e.  muscle  containing  both  red  and  white  fibres. 

Since  the  sarcous  element  represents  the  contractile  unit  of  the 
muscle,  a  knowledge  of  its  intimate  structm-e  should  be  of  great 
importance  for  the  theory  of  muscular  contraction.  Unfortunately, 
however,  we  are  here  at  the  limits  of  the  demonstrably  visible.     It 


Fig.  38.    Fibrils  of  the  wing-muscles  of  a  wasp,  prepared  by  RoUet's  method. 
Highly  magnified.     (E.  A.  ScHAFKii.) 
A,  a  contracted  fibril.     B,  a  stretched  fibril,  with  its  sarcous  ekments 
separated  at  the  line  of  Hensen.     c,  an  uncontracted  fibril,  showing  the 
porous  structure  of  the  sarcous  elements. 

becomes  difficult  to  determine  how  far  the  appearances  observed 
under  the  microscope  are  due  to  actual  structural  differences  or  are 
produced  by  the  unequal  diffraction  of  light  by  the  varying  elements 
of  the  muscle  fibre.  All  observers  are  agreed  that  the  essential 
contractile  element  is  the  row  of  sarcous  elements  forming  the  muscle 
fibril  or  sarcostyle.  Schafer,  working  on  the  highly  differentiated 
wing-muscle  of  the  wasp,  concludes  that  each  sarcostyle  is  divided  by 
Krause's  membranes  (the  fines  in  the  middle  of  each  light  stripe)  into 
sarcomeres.  Each  sarcomere  contains  a  darker  substance  near  the 
centre  divided  into  two  parts  by  Hensen's  disc.  At  each  end  of  the 
sarcomere  the  contents  ai-e  clear  and  hyaline.  In  the  act  of  contraction, 
the  clear  material  flows,  according  to  Schafer,  into  tubular  pores  in 
the  central  dark  material. 


SJL 


Fig.  3!^  Diagram  of  a  sarcomere  in  a 
moderately  extended  condition.  A,  and 
in  a  contracted  condition,  B  ;  K,  k, 
membranes  of  Krause ;  H,  line  or  plane 
of  Hensen  ;  se,  poriferous  sarcous 
element.     (Schafee.) 


THE  STRUCTUKE  OF  VOLUNTARY  MUSCLE    20.T 

Most  histologists  agree  in  assigning  to  the  middle  part  of  the 
sarcous  element  a  denser  structure  than  to  the  two  ends.  According 
to  Macdougall,  however,  the  lighter  appearance  at  each  end  of  the 
sarcous  element  is  an  optical  illusion.  He  regards  the  sarcous  element 
as  a  cylindrical  bag  with  homogeneous  contents,  crossed  only  by  one 
or  three  delicate  transverse  membranes.  Krause's  membrane  would 
be  rigid,  while  the  lateral  wall 
of  the  sarcous  element  is  exten- 
sible, and  is  folded  longitudinally, 
so  that  it  can  bulge  out  and 
produce  a  shortening  and  thick- 
ening of  the  whole  sarcous  ele- 
ment if  by  any  means  the  pres- 
sure be  raised  in  its  interior.  In 
favour  of  a  difierentiation  within 
the  sarcous  element  itself  is  the 
fact  that  under  certain  conditions 
it  is  possible  to  produce  a  preci- 
pitate, limited  only  to  the  central  part  of  the  sarcouselement,  i.e.  the 
part  to  which  Schafer  assigns  a  tubular  structure. 

When  a  muscle  fibre,  killed  by  osmic  acid  or  alcohol,  is  examined 
under  the  microscope  by  polarised  hght,  it  is  seen  to  be  made  up  of 
alternate  bands  of  singly  and  doubly  refracting  material.  The  doubly 
refracting  [anisotro'pous)  substance  corresponds  to  the  dark  band,  and 
the  singly  refracting  [isotwpous)  to  the  light  band.  If  the  living 
fibre  be  examined  in  the  same  way,  it  is  found  that  nearly  the  whole 
of  it  is  doubly  refracting,  the  singly  refracting  substance  appearing 
only  as  a  meshwork  with  long  parallel  meshes  corresponding  to  the 
muscle  prisms.  In  short,  in  a  living  fibre  the  muscle  prisms  are 
anisotropous,  the  sarcoplasm  isotropous. 

When  a  muscle  fibre  contracts,  there  is  an  apparent  reversal  of  the 
situations  of  the  light  and  dark  stripes,  owing  to  the  fact  that  the 
interstitial  sarcoplasm  is  squeezed  out  from  between  the  bulging 
sarcomeres,  and  accumulates  on  each  side  of  the  membranes  of  Krause. 
The  accumulation  of  sarcoplasm  in  this  situation  makes  the  previously 
light  strife  appear  dark,  and  the  dark  striae  by  contrast  hghter  than 
they  were  before.  That  there  is  no  true  reversal  of  the  stria?  is  shown 
by  examining  the  muscle  by  polarised  hght,  the  two  substances, 
isotropous  and  anisotropous,  retaining  their  relative  positions. 

Every  skeletal  muscle  is  connected  with  the  central  nervous 
system  by  nerve  fibres,  some  conveying  impressions  from  the  muscle 
to  the  centre,  the  others  acting  as  the  path  of  the  motor  impulses  from 
the  centre  to  the  muscle.  These  latter — the  motor  nerves— end  in 
the  muscular  fibre  itself,  by  means  of  a  special  end- organ — the  motor 


204 


PHYSIOLOGY 


end-plate.  The  neurilemma  of  the  nerve  fibre  becomes  continuous 
with  the  sarcolemma,  the  medullary  sheath  ends  suddenly,  while  the 
axis  cylinder  ramifies  in  a  mass  of  undifferentiated  protoplasm,  con- 
taining nuclei,  and  lying  in  contact  with  the  contractile  substance  of 
the  muscle  immediately  under  the  sarcolemma  (Fig.  40).     This  mass 

of  protoplasm  is  known  as  the 
'  sole  plate.'  It  is  not  marked 
in  all  animals.  Thus  in  the  frog 
the  axis  cylinder  ends  in  a  series 
of  branches  at  right  angles  to  one 
another,  distributed  over  a  con- 
siderable length  of  the  muscle  fibre. 
The  sole  plate  in  this  case  seems 
to  be  limited  to  scattered  nuclei 
lying  in  close  contact  with  the 
terminal  branches  of  the  nerve 
fibre.  So  far  as  we  can  tell  at 
present,  the  ultimate  ramifications 
of  the  axis  cylinder  end  freely  and 
do  not  enter  into  organic  connec- 
tion with  the  contractile  substance 
itself. 

Most  of  our  knowledge  on  the 
subject  of  muscle  has  been  derived 
from  the  study  of  the  gastroc- 
nemius and  sartorius  muscles  of 
the  frog.  The  position  of  these 
muscles  is  shown  in  the  accom- 
panying diagram  (Fig.  41).  The 
gastrocnemius,  which,  with  the 
attached  sciatic  nerve,  is  most  fre- 
([uently  employed  as  a  nerve- 
muscle  preparation,  forms  a  thick  belly  immediately  under  the  skin  at 
the  back  of  the  leg,  and  arises  by  two  tendons  from  the  lower  end  of 
the  femur  and  the  outer  side  of  the  knee-joint.  The  two  tendons 
converge  towards  the  centre  of  the  muscle,  uniting  about  its  middle,  and 
from  them  a  number  of  short  muscular  fibres  arise,  passing  backwards 
and  dorsally  to  be  inserted  into  a  flat  aponeurosis  covering  the  lower 
half  of  the  muscle,  which  ends  in  the  tendo  Achillis.  On  account  of 
this  irregular  arrangement  of  the  muscular  fibres,  the  gastrocnemius 
can  only  be  employed  when  the  contraction  of  the  muscle  as  a  whole  is 
the  object  of  investigation.  The  effective  cross-area  of  the  fibres  is 
much  greater  than  the  actual  cross-section  of  the  muscle,  so  that, 
while  the  actual  shortening  of  the  gastrocnemius  is  but  small,  its 
strength  of  contraction  is  considerable. 


Fig 


lizard, 


40.  Motor  end-organ  of  a 
gold  preparation.  (Kuhne.) 
n,  nerve  fibre  dividing  as  it  ap- 
proaches the  end-organ;  r,  ramifica- 
tion of  axis  cylinder  npcjn  b,  granu- 
lar bed  or  sole  of  the  end-organ  ;  m, 
clear  siibstance  surrouniling  the 
ramifications  of  the  axis  cylinder. 


THE  STRUCTURE  OF  VOLUNTARY  MUSCLE  205 

The  sartorius  muscle  consists  of  a  thin  band  of  muscle  fibres 
running  parallel  from  one  end  of  the  muscle  to  the  other.  It  lies  on 
the  ventral  surface  of  the  thigh,  arising  from  the  symphysis  pubis  by 
a  thin  flat  tendon,  and  is  inserted  by  a  narrow  tendon  into  the  inner 
side  of  the  head  of  the  tibia.  On  account  of  the  regularity  with  which 
its  fibres  are  disposed,  this  muscle  is  of  especial  value  in  experiments 
on  the  local  conditions  of  a  muscle  fibre  accompanying  its  activity. 


Tib.  ant.  loii}; 


Teiido  Acliillis 


Fig.  41.     Muscles  of  hinder  extremity  of^og.     (After  Eckeb.) 

When  a  greater  mass  of  approximately  parallel  fibres  is  necessary, 
recourse  may  be  had  to  a  preparation  consisting  of  the  gracilis  and 
semi-membranosus  muscles  together.  This  latter  muscle  lies  dorsallv 
to  the  gracilis  muscle  which  is  shown  in  the  illustration. 

Other  muscles  in  the  frog  used  for  particular  purposes  are  the 
mylohyoid  and  the  dorsocutaneous  muscles.  Tlie  mylohyoid  muscle 
of  the  frog,  which  lies  on  the  ventral  surface  of  the  tongue,  has  the 
advantage  that  its  fibres  lie  in  close  contact  with  a  lymph-space 
occupying  the  centre  of  the  tongue.  If  any  drug  be  injected  into 
this  lymph-space  it  acts  with  extreme  rapidity  on  the  muscle  fibres, 
so  that  the  tongue- preparation  of  the  frog  is  a  useful  one  for  the  study 
of  the  action  of  different  substances  on  muscle  fibres. 


SECTION  II 

EXCITATION  OF  MUSCLE 

A  MUSCLE  may  be  caused  to  contract  in  various  ways.  Normally 
it  contracts  only  in  response  to  impulses  starting  in  the  central  nervous 
system  and  transmitted  down  the  nerves.  But  contraction  may  be 
artificially  excited  in  various  ways  in  a  muscle  removed  from  the  body. 
If  we  make  a  muscle-nerve  preparation  {i.e.  a  muscle  with  as  long  a 
piece  of  its  nerve  as  possible  attached  to  it),  such  as  the  gastrocnemius 
of  the  frog  with  the  sciatic  nerve,  we  find  we  can  cause  contraction 
bv  various  forms  of  stimuli — mechanical,  thermal,  or  electrical — 
apphed  to  the  muscle  or  the  nerve  (direct  and  indirect  stimulation). 
Thus  the  muscle  responds  with  a  twitch  if  we  pass  an  induction  shock 
through  it  or  its  nerve,  or  pinch  either  with  a  pair  of  forceps.  Or  we 
may  use  chemical  stimuli,  and  cause  contraction  by  the  apphcation 
of  strong  glycerin  or  salt  solution  to  the  nerve. 

These  experiments  do  not  prove  conclusively  that  muscle  itself  is 
irritable.  It  might  be  urged  that,  when  we  pinched  or  burnt  the 
muscle  we  stimulated,  not  the  muscle  substance  itself,  but  the  terminal 
ramifications  of  the  nerve  in  the  muscle,  and  that  these  in  their  turn 
incited  the  muscle  to  contract.  But  the  independent  excitability  of 
muscle  is  shown  clearly  by  the  following  experiment  by  Claude 
Bernard. 

A  frog,  whose  brain  has  been  previously  destroyed,  is  pinned  on  a 
board,  and  the  sciatic  nerves  on  each  side  exposed.  A  ligature  is  then 
passed  round  the  right  thigh  underneath  the  nerve,  and  tied  tightly 
80  as  to  effectually  close  all  the  blood-vessels  supplying  the  limbs, 
without  interfering  with  the  blood-supply  to  the  nerve.  Two  drops 
of  a  1  per  cent,  solution  of  curare  are  then  injected  into  the  dorsal 
lymph-sac.  After  the  lapse  of  a  quarter  of  an  hour  it  is  found  that 
the  strongest  stimuli  may  be  applied  to  the  left  sciatic  nerve  without 
causing  any  contraction  of  the  muscles  it  supplies.  On  the  right 
side,  stimulation  of  the  nerve  is  as  efficacious  as  before.  Both 
Xocnemii  respond  readily  to  direct  stimulation,  showing  that  the 
musclfes  are  not  affected  by  the  drug.  Since  both  sciatic  nerves  have 
beeiL  eS^osed  to  the  influence  of  the  curare,  it  is  evident  that  the 
difference  on  the  two  sides  cannot  be  due  to  any  deleterious  effect  on 
them  by  the  curare.    We  have  also  excluded  the  muscles  themselves ; 

206 


EXCITATION  OF  MUSCLE 


207 


so  we  must  conclude  that  the  curare  paralyses  the  muscles  by  affecting 
the  terminations  of  the  nerve  within  the  muscle,  and  probably  the 
end-plates  themselves.  This  experiment  teaches  us  that  muscle  can 
be  excited  to  contract  by  direct  stimulation,  even  when  the  terminal 
ramifications  of  the  nerve  within  it  are  paralysed,  so  that  stimulation 
of  them  would  be  without  effect. 

The  same  fact  may  be  demonstrated  in  a  different  way  by  means 
of  chemical  stimuli.  It  is  found  that  whereas 
strong  glycerin  excites  nerve  fibres,  it  is  with- 
out effect  on  muscle  fibres  ,  while  on  the  other 
hand  weak  ammonia  is  a  strong  excitant  for 
muscle,  but  is  without  effect  on  nerve.  If  the 
frog's  sartorius  be  dissected  out  and  the  lower 
end  dipped  in  glycerin,  no  effect  is  produced. 
On  snipping  off  the  lower  third  of  the  muscle 
and  then  immersing  the  cut  end  in  glycerin, 
a  twitch  at  once  occurs.  The  lower  end  con- 
tains no  nerve  fibres  (Fig.  42),  and  it  is  only 
when  a  section  containing  nerve-fibres  is  ex- 
posed to  the  action  of  glycerin  that  contraction 
takes  place.  On  the  other  hand,  mere  exposure 
of  muscle  to  the  vapour  of  dilute  ammonia 
causes  contraction  (and  subsequent  death), 
although  the  nerve  to  the  miiscla  can  be 
immersed  in  the  solution  without  any  excitation 
being  produced. 

Of  all  the  different  stimuli  that  we  have  mentioned  as  capable  of 
exciting  muscular  contraction,  the  electrical  is  that  most  frequently 
employed.  It  is  easy,  using  this  form.,  to  graduate  accurately  the 
intensity  and  duration  of  the  stimulus.  At  the  same  time  the  stimulus 
may  be  appUed  many  times  to  any  point  on  the  muscle  or  nerve  with- 
out killing  the  part  stimulated,  whereas  with  other  forms  of  stimulus 
it  is  difiBcult  to  obtain  excitatory  effects  without  injuring  to  a  greater 
or  less  extent  the  part  stimulated. 

METHODS  EMPLOYED  FOR  THE  STIMULATION  OF  MUSCLE  AND 
NERVE.  The  two  commonest  form.s  of  electrical  stimuli  emplo3-ed  are  (I)  the 
make  and  break  of  a  constant  ciurent,  (2)  the  induction  currents  of  high  inten- 
sity and  short  duration  obtained  from  an  induction  coil. 

(1)  Constant  Cxxbrent.  As  a  source  of  constant  current  a  Daniell's  cell 
is  generally  employed.  This  consists  of  an  outer  pot  containing  a  saturated 
solution  of  copper  sulphate,  in  which  is  immersed  a  copper  cylinder.  To  the 
cjiinder  at  the  top  a  binding  screw  is  attached,  by  which  the  coimection  of  the 
copper  with  a  wire  terminal  is  effcctecL  Within  the  copper  cylinder  is  a  second 
pot  of  porous  clay,  filled  with  dilute  siolphiuic  acid,  in  which  is  immersed  a  rod 
of  amalgamated  zinc.  In  this  cell  the  zinc  is  the  positive  and  the  copper  the 
negative  dement.     Hence  the  current  flows  (in  the  cell)  from  una  to  copper. 


Fig.  42.  The  ramification 
of  the  nerve  fibres 
within  the  sartorius 
muscle  of  the  frog, 
showing  the  freedom 
of  the  lower  portion 
of  the  muscle  from 
nerve  fibres.    (Kuhne.) 


208  PHYSIOLOGY 

and  if  the  binding  screws  of  the  two  elements  are  connected  by  a  wire,  the 
current  flows  in  the  wire  (outer  circuit)  from  copper  to  zinc,  thus  completing 
the  circuit.  iSince  in  the  outer  circuit  the  current  flows  from  copper  to  zinc, 
the  terminal  attached  to  the  copper  is  called  the  positive  pole,  and  that  to  the 
zinc  the  negative  pole.  When  the  current  is  required  to  be  very  constant,  the 
zinc  may  be  immersed  in  a  saturated  solution  of  zinc  sulphate  instead  of  dilute 
sulphuric  acid.  A  Daniell's  cell,  though  very  constant,  gives  only  a  small 
current,  owing  to  its  small  electromotive  force  and  high  internal  resistance. 

When  a  stronger  current  is  required  it  is  best  to  use  a  storage  battery.  In 
this,  when  charged,  the  two  elements  are  lead  and  lead  oxide,  Pb02.  It  has  the 
advantage  that  it  may  be  used  over  and  over  again,  being  recharged  through 
a  resistance  from  the  electrical  mains  when  it  has  run  down. 

Another  very  convenient  form  of  battery,  though  not  so  constant  as  the 
two  forms  just  described,  is  the  bichromute  battery,  with  a  single  fluid.  This 
consists  of  a  plate  of  zinc  between  two  plates  of  carbon.  The  whole  are  arranged 
so  that  they  can  be  immersed  in  or  drawn  out  of  the  fluid  at  pleasure.  The 
fluid  used  is  a  mixture  of  sulphuric  acid  and  potassium  bichromate.  The  wire 
attached  to  the  carbons  is  the  positive  pole  and  the  current  in  the  outer  circuit 
flows  from  carbon  to  zinc. 

Another  useful  type  of  cell  is  the  Leclanche  cell.  This  consists  of  a  glass 
jar  containing  a  solution  of  sal-ammoniac.  Into  this  dips  an  amalgamated 
rod  of  zinc,  which  is  the  positive  plate.  A  piece  of  gas  carbon  forms  the  negative 
plate.  This  is  surrounded  by  peroxide  of  manganese  (]\In02)  which  is  kept  in 
contact  with  the  surface  of  the  carbon  by  being  placed  in  a  porous  pot.  In 
some  forms  of  Leclanche  the  manganese  and  carbon  are  ground  up  together 
and  pressed  into  a  cylinder  which  surrounds  the  zinc  rod.  When  the  cell  is  on 
open  circuit — that  is,  when  the  terminals  are  not  connected  and  no  current  is 
passing — very  little  action  takes  place  ;  but  when  the  circuit  is  closed  and 
the  current  passes,  the  zinc  dissolves  in  the  sal-ammoniac,  forming  a  double 
chloride  of  zinc  and  ammonia,  while  ammonia  gas  and  hydrogen  are  liberated  at 
the  carbon  pole.  The  nascent  hydrogen  reduces  the  peroxide  of  manganese  and 
so  polarisation  is  prevented.  On  account  of  its  great  solubility  in  water  the 
ammonia  has  no  polarising  action.  The  Leclanche  is  a  convenient  form  of  cell, 
as  when  once  set  up  it  requires  a  minimxim  of  attention.  If  it  is  worked 
through  a  considerable  resistance,  it  Avill  keep  in  order  for  some  time,  par- 
ticularly if  the  work  is  intermittent  ;  but  if  it  is  used  vnth.  a  small  resistance 
in  circuit  it  polarises  very  rapidly.  The  E.M.P.  of  one  Leclanche  cell  is  1-4 
volt  in  the  external  circuit.  The  positive  current  is  conventionally  said  to 
run  from  the  zinc  to  the  carbon  in  the  cell,  and  from  the  carbon  to  the  zinc 
in  the  circuit  outside.  The  wire  attached  to  the  carbon  is  the  'positive  pole, 
that  to  the  zinc  the  negative  pole.  Dry  cells  are  usually  Leclanche  cells,  in 
which  the  solution  of  sal-ammoniac  is  prevented  from  spilling  by  absorption 
with  sawdust  or  plaster  of  Paris.  Tlie  E.M.F.  is  the  same  as  (he  I^eclanche, 
but  they  polarise  much  more  readily. 

If  the  poles  of  a  Daniell's  cell  be  connected  by  wires  with  a  nerve  or  muscle 
of  a  nerve-muscle  preparation  (as  in  Fig.  43),  the  current  will  flow  from  copper 
to  the  nerve  at  A,  and  along  the  nerve  from  A  to  K.  At  K  the  current  will 
leave  the  nerve  to  flow  to  the  zinc  of  the  battery,  so  completing  the  circuit. 
The  point  at  which  the  current  enters  the  nerve  (i.e.  the  point  of  the  nerve 
connected  with  the  positive  pole  of  the  battery)  is  called  the  anode,  and  the 
point  at  which  the  cvu^rent  leaves  the  nerve  is  called  the  cathode.  The  wires 
by  which  the  ciurent  is  conducted  to  and  from  the  nerve  are  called  the  elec- 
trodes. As  electrodes  we  generally  employ  two  platinum  wires  mounted  together 
on  a  piece  of  vulcanite. 


EXCITATION  OF  MUSCLE 


209 


For  the  purpose  of  making  or  breaking  the  current  at  will,  various 
forms  of  keys  are  employed.  Tlie  ordinary  make  and  break  key  consists  of 
a  hinged  wiie  dipping  into  a  mercury  cup.  When  the  wire  is  depressed  so 
that  it  dips  into  the  mercury,  the  circuit  is  complete.  On  raising  the  wire  by 
means  of  the  handle,  the  circuit  is  broken. 


Mri/e. 


Du  Bois  Raymond's  key  consists  of  two  pieces  of  brass,  each  of  which  has 
two  binding  screws  for  the  attachment  of  wires.  These  are  connected  by  a 
third  piece,  or  bridge,  which  is  jointed  to  one  of  the  two  side  bits,  so  that  it 
may  be  raised  or  lowered  at  pleasure  {v.  Fig.  44).  It  may  be  used  either  as 
a  simple  make-and-break  key,  or,  as  is  more  usual,  as  a  short-circuiting  key. 
In  the  first  case  one  brass  bank  is  attached  to  one  terminal,  the  other  to  the 
other  terminal.  If  the  bridge  be  now  lowered,  the  connection  is  made  and 
the  current  passes.  If  the  bridge  be  raised,  the  current  is  broken.  Fig.  44  a 
and  B  show  the  way  in  which  the  key  is  arranged  for  short-circuiting.  It 
wiU  be  seen  that  four  wires  are  attached  to  the  key  ;  two  going  to  the 
battery,  and  two  we  may  suppose  going  to  a  nerve.  When  the  bridge  is 
down,  as  in  Fig.  44  a,  the  current  from  the  cell  on  coming  to  the  key  has  a 
choice  of  two  routes.  It  may  either  go  through  the  brass  bridge,  or  through 
the  other  wires  and  nerve.  The  resistance  of  the  nerve  however  is  about  100,000 
ohms,  whereas  that  of  the  bridge  is  not  the  thousandth  part  of  an  ohm.  Wlien 
a  cxurent  divides,  the  amoxmt  of  current  that  goes  along  any  branch  is  inversely 
proportional   to   the  resistance.     Here   the  resistance  in  the   nerve-circuit  is 


Fig.  44.     Du  Eois  key,  closed.     Du  Bois  key,  open. 

practically  infinite  compared  with  that  in  the  brass  bridge,  and  so  all  the  curroi.t 
goes  through  the  bridge  and  none  through  the  nerve.  We  say  then  that  the 
current  is  short-circuited. 

It  is  often  necessary  to  reverse  the  direction  of  a  current  through  a  nerve- 
muscle  preparation  or  a  galvanometer  in  the  course  of  an  experiment.  For 
this  purpose  Pohl's  reverser  may  be  used.  It  consists  of  a  slab  of  ebonite  or 
paraffin  or  other  insulating  material,  in  which  are  six  small  holes  filled  •nitii 
mercur3^  A  binding  screw  is  in  connection  with  the  mercury  in  each  of  these 
holes.  Two  cross-wires  (not  in  contact  with  one  another)  join  two  sets  of  pools 
together,  as  shown  in  Fig.  45.     A  cradle  consisting  of  two  wires  joined  by  an 

14 


210 


PHYSIOLOGY 


iusulating  handle  carries  two  arcs  of  wire  by  which  the  pools  at  a  and  5  may 
be  put  into  connection  with  either  x  and  y,  or  the  corresponding  pools  on 
the  opposite  side.  It  •will  be  seen  that  with  the  cradle  tipped  to  one  side,  as 
in  Fig.  45  A,  the  current  from  the  battery  enters  the  reverser  at  a  ;  this 
proceeds  up  the  Arae  of  the  cradle,  down  towards  the  right,  then  along  the 
cross-wire  to  the  pool  at  x.  x  is  therefore  the  anode,  and  y  the  cathode. 
In  Fig.  45  B  the  cradle  has  been  swung  over  to  the  other  side.  Here  the 
cross-wires  are  not  used  at  all  by  the  current,  which  passes  from  a  up  the  sides 
and  down  the  curved  wire  to  y.  In  this  case  y  is  now  the  anode  and  x 
the  cathode,  and  the  direction  of  the  current  through  the  circuit  connected 
with  X  and   y    is  reversed.     By  taking  out  the  cross-wires,    Pohl's   reverser 


Fk!.  45.     Diagram  of  Pohl's  reverser. 


may  be  used  as  a  simple  switch,  by  which  the  current  may  be  led  into  two 
different  circuits  in  turn. 

With  this  form  of  reverser  difficulty  is  often  experienced  owing  to  dirt 
accumulating  on  the  mercviry  and  forming  an  insulating  layer  between  it  and 
the  binding  screw  or  copper  wire.  Several  improved  forms  of  reverser  are 
now  made  where  the  mercury  poles  are  replaced  by  brass  banks,  and  these  are 
generally  to  be  preferred  in  iJractice. 

(2)  Induced  Currents.  In  using  these  the  muscle  or  nerve  is  stimulated 
by  the  current  of  momentary  duration  produced  in  the  secondary  circuit  of 
an  induction-coil  by  the  make  or  break  of  a  constant  ciu-rent  in  the  primary. 

The  construction -of  the  induction-coil  or  inductor  ium  is  founded  on  the  fact 
that  if  a  coU  of  wire  in  connection  with  a  galvanometer  be  placed  close  to  (but 
insulated  from)  another  coil  through  which  a  current  may  be  led  from  a  battery, 
it  is  found  that  on  make  and  break  of  the  current  of  the  second  coil  a  momentary 
current  is  induced  in  the  first.  The  induced  current  on  make  is  in  the  reverse 
direction,  that  on  break  in  the  same  direction  as  the  primary  current.  The 
electromotive  force  of  the  induced  current  is  proportional  to  the  njipiber  of 
turns  of  wire  in  the  coils.  The  induction-coil  consists  of  two  coils,  each  con- 
taining many  turns    of    wire.      The  smaller  coil  (Rj,  Fig.  46),  consisting  of  Vk 


EXCITATION  OF  MUSCLE 


211 


few  turns  of  comparatively  thick  wire,  is  the  primary  coil,  and  is  put 
into  connection  with  a  battery.  It  has  within  it  a  core  of  soft  iron  wires,  which 
has  the  effect  of  attracting  the  lines  of  force,  concentrating  them,  and  so 
increasing  its  power  of  inducing  secondary  currents.  The  secondary  coil,  Rg, 
of  a  large  number  of  turns  of  very  thin  wire,  is  arranged  so  as  to  slide  over  the 
primary  coil.  It  is  provided  with  two  terminals,  wliich  may  bo  comiected 
with  the  nerve  or  other  tissue  that  we  wish  to  stimulate.  Since  the  electro- 
motive force  of  the  induced  current  is  proportional  to  the  number  of  turns 
of  wiio,  it  is  evident  that  the  electromotive  force  of  the  current  delivered  by 
the  induction  coil  may  bo  many  thousand  times  that  of  the  battery  current 
flowing  through  the  primary  coil.  The  induced  currents  increase  rapidly  in 
strength  as  the  coils  are  approached  to  one  another  ;  the  strength  of  these 
therefore  may  bo  regulated  by  shoving  the  secondary  up  to  or  away  from  the 
primary  coil. 


Fia,  46.     Diagram  of  inductorium.     Ep  primary  ;    r.j,   secondary  coil. 
m,  electro-magnet  of  Wagner's  hammer,    tc,  Helmholtz's  side  wire. 


A  short-circuiting  key  is  always  placed  between  the  secondary  coil  and  the 
nerve  to  be  stimulated.  If  only  single  induction  shocks  are  to  be  used,  a 
make-and-break  key  is  put  in  the  primary  battery  circuit,  and  the  two  wires 
from  the  battery  and  key  arc  attached  to  the  two  top  screws  of  the  primary 
coil  (c  and  d,  Fig.  46).  It  is  then  found  that  the  shock  given  by  the  induced 
current  on  break  of  the  primary  current  is  much  stronger  than  that  on  make. 

In  endeavouring  to  explain  this  difference  in  the  intensity  of  the  make- 
and-break  induction  shocks,  it  must  be  remembered  that  the  intensity  of  the 
momentary  current  induced  in  tlio  secondary  coil  at  make  or  break  of  the 
primary  current  is  proportional  (1)  to  the  number  of  turns  of  wire  in  each  coil  ; 
(2)  inversely  to  the  mean  distance  between  the  coils  {i.e.  tho  nearer  the  coils, 
the  stronger  the  induced  current)  ;  (3)  to  the  rate  of  change  in  strength  of  the 
primary  cm-rent.  Now,  when  a  current  is  made  through  tho  primary  coil, 
induction  takes  place,  not  only  between  primary  and  secondary  coils,  but 
also  between  the  individual  turns  of  tho  primary  coil  itself.  Tliis  ciurent  of 
self-induction,  being  opposed  in  direction  to  the  battery  current,  hinders  and 
delays  the  attainment  by  tho  latter  of  its  full  strength,  and  so  slows  the  rale 
of  change  of  current  in  the  primary  coil.  Hence  the  intensity  of  tho  momentary 
current  induced  in  tho  secondary  coil  is  less  than  it  would  have  been  without 
tho  retarding  effect  of  self-induction.  At  break  of  the  cm-rent,  an  extra  cm-rent 
is  also  produced  iu   tho   primary  coil  in   tho  samo    direction   as    tho    battery 


212 


PHYSIOLOGY 


current,  and  therefore  tending  to  reduce  the  rate  of  change  of  the  current  from 
full  strength  to  nothing.  In  this  case,  however,  the  primary  circuit  being 
broken,  the  cmrent  of  self-induction  cannot  pass  without  jumping  the  great 
resistance  offered  by  the  air,  so  that  its  retarding  effect  on  the  rate  of  disappear- 
ance of  the  primary  current  may  be  practically  disregarded.  In  Fig.  47  the 
line  a,  b,  c,  d,  will  represent  the  changes  occurring  in  the  primary  current  at 
make  and  break,  a  b  corresponding  to  the  make  and  c  d  to  the  break.  The 
lower  line  represents  the  momentary  cm-rents  induced  in  the  secondary  circuit, 
m  being  the  current  of  low  intensity  and  long  duration  produced  by  the  make, 
and  B  the  shock  of  high  intensity  and  short  duration  caused  by  the  sharp 
break  of  the  primary  current. 

When   we   desire   to   use  faradic   stimulation — that  is,   secondary  induced 
shocks  rapidly  repeated  50  to  100  times  a  second — we  make  use  of  the  apparatus 


(c^ 


Fig.  47. 


attached  to  the  coil,  known  as  Wagner's  hammer  (Figs.  48a  and  48b).  In  this 
case  the  wires  from  the  battery  are  comiected  to  the  two  lower  screws  (a  and  b, 
Fig.  46).  Fig.  48a  shows  the  direction  of  the  cturent  when  Wagner's  hammer 
is  used.  The  current  enters  at  a,  riuis  up  the  pillar  and  along  the  spring  to 
the  screw  x.  Here  it  passes  up  through  the  screw,  and  through  the  primary 
coil  B[.  From  the  primary  coil  it  passes  up  the  small  coil  m,  and  from  this 
to  the  terminal  b  and  back  to  the  battery.  But  in  this  co\u?se  the  coil  m 
is  converted  into  an  electro-magnet.  The  hammer  h  attached  to  the  spring 
is  attracted  down,  and  so  the  spring  is  drawn  away  from  the  screw  x,  and  the 
current  is  therefore  broken.  The  break  of  the  cmrent  destroys  the  magnetic 
power  of  the  coil,  the  spring  jumps  up  again  and  once  more  makes  circuit  with 
the  screw  x,  only  to  be  drawn  down  again  directly  this  occurs.  In  this  way 
the  spring  is  kept  vibrating,  and  the  primary  circuit  is  continually  made  and 
broken,  with  the  production  at  each  make-and-break  of  an  induced  current 
in  the  secondary  coil. 

It  is  evident  that,  when  the  primary  current  is  made  and  broken  fifty  times 
in  the  second,  there  will  be  a  hundred  momentary  currents  produced  during 
the  same  period  in  the  secondary  coil.  Every  alternate  one  of  these  produced 
by  the  break  of  current  in  the  primary  will  be  much  stronger  than  the  inter- 
vening currents  produced  by  the  make.  In  order  to  equalise  make  and  break 
induction -shocks,  so  that  a  regular  series  of  momentary  currents  of  nearly  equal 
intensity  may  be  produced,  the  arrangement  known  as  Hclmholtz's  is  used, 


EXCITATION  OF  MUSCLE 


213 


In  this  arrangement  the  side  wire  w,  shown  in  Fig.  46,  and  diagrammatically 
in  Fig.  48b,  is  used  to  connect  the  binding  screw  o  with  the  binding  screw 
c  at  the  top  of  the  coil.  The  screw  z  is  raised,  so  as  not  to  touch  the  spring, 
and  the  lower  screw  y  is  moved  up  till  it  comes  nearly  in  contact  with  the 
under  surface  of  the  spring.  If  we  consider  the  direction  of  the  current  now, 
we  see  that  it  enters  as  before  at  the  terminal,  travels  up  the  Helmholtz's  wire 
w  to  the  screw  c,  thence  through  the  primary  coil  Ri,  then  through  the 
coil  m  of  the  Wagner's  hammer,  and  so  back  to  the  battery.  The  coil  m, 
thus  becoming  an  electro-magnet,  draws  down  the  hammer  h.  In  this  act 
the  under  surface  of  the  spring  comes  in  contact  with  the  screw  y.  The 
ciurrent  then  has  a  choice  of  two  ways.  It  may  either  go  through  the  coil  as 
before,  or  take  a  short  cut  from  the  terminal  a,  up  the  pillar,  along  the  spring, 
through  the  screw  y,  and  down  to  the  terminal  b  back  to  the  battery.  As 
the  resistance  of  this  latter  route  is  very  small  compared  with  the  resistance 
of  the  primary  coil,  &c.,  the  greater  part  of  the  current  takes  this  way.  The 
infinitesimal  current  which  now  passes  through  the  coil  of  Wagner's  arrange- 
ment is  insufficient  to  magnetise  this,  and  the  hammer  springs  up  again  ;   thus 


.^-X 


Fig.  48a.  Diagram  sho^^'ing  course  of 
current  in  inductorium  when  Wagner's 
hammer  is  used. 


Fig.  48b.  Diagram  showing  course  of 
ciuTent  when  the  Helmholtz  side  wire 
is  used. 


the  process  is  restarted,  and  the  spring  vibrates  rhythmically.  With  this 
arrangement  the  primary  current  is  never  broken,  but  only  short-circuited, 
and  so  diminished  very  largely.  Hence  the  retarding  influence  of  self-induction 
is  as  potent  with  break  as  with  make  of  the  current,  and  the  eflfects  on  the 
secondary  coil  in  the  two  cases  are  approximately  equal.  In  Fig.  47  ce 
represents  the  change  in  the  primary  current  when  the  current  is  short-circuited 
instead  of  being  broken,  and  b  represents  the  effect  produced  in  the  secondary 
coil.  It  will  bo  seen  that  the  currents  m  and  b  are  practically  identical 
in  intensity  and  duration. 

When  the  induction-coil  is  used  for  stimulating,  it  is  usual  to  graduate  the 
strength  of  the  shock  administered  to  the  excitable  tissue  by  moving  the 
secondary  coil  nearer  to  or  further  away  from  the  primary  coil.  It  must  he 
remembered  that  the  strength  of  the  induced  current  does  not  vary  in  numerical 
proportion  with  the  distance  of  the  two  coils  from  one  another.  If  one  coil 
is  some  distance,  say,  20  cms.  from  the  primary  coil,  the  induced  current  pro- 
duced by  make  or  break  of  the  primary  current  is  very  small,  and  on  moving 
the  secondary  from  20  up  to  10  cms.  the  increase  in  strength  of  the  ciurent 
will  not  be  very  rapid.  The  increase  will  however  become  more  and  more  rapid 
as  the  two  coils  are  brought  closer  together.  Using  the  same  strength  of  current 
in  the  primary  coil  and  the  same  resistance  in  the  secondary  coil,  we  can  say 


214 


PHYSIOLOGY 


that  the  make  or  break  current  will  be  uniform  so  long  as  the  distance  of  the 
coils  remains  constant.  We  are  not  able  however  to  say  by  how  much  the 
current  will  increase  as  the  secondary  coil  is  moved,  say,  from  11  to  10  cms. 
distant  from  the  primary  coil.  If  it  is  required  to  know  the  exact  increment 
in  the  exciting  ciurent  which  is  used,  it  is  necessary  to  graduate  the  induction- 
coil  by  sending  the  induction  shocks,  obtained  at  different  distances  of  secondary 
from  primary  coil,  through  a  ballistic  galvanometer. 

Another  method  which  may  be  adopted  for  the  excitation  of  muscle  or 
nerve  is  the  discharge  of  a  condenser.  The  advantage  of  this  method  is  that 
we  can  determine  not  only  the  amount  of  electricity  discharged  through  the 
preparation,  but  the  actual  energy  employed.  If  two  plates  of  metal  separated 
from  one  another  by  a  thin  insulating  layer  of  dielectric  such  as  air,  glass,  mica, 
or  paraffined  paper,  be  connected  with  the  two  poles  of  a  battery,  each  plate 

acquires  the  potential  of  the  pole  of  the  battery 
with  which  it  is  connected,  and  receives  therefrom 
a  charge  of  electricity  (positive  or  negative).  If 
the  connections  be  broken  the  two  plat-es  retain 
their  charge.  If  now  they  be  connected  by  a  wire 
they  discharge  through  the  -wire,  and  if  a  nerve  be 
inserted  in  the  cotu-se  of  the  vnie,  it  may  be  excited 
by  the  discharge. 

The  amount  of  electricity,  that  may  be  stored 
up  in  this  way,  will  depend  on  the  extent  of  the 
plates  and  their  proximity  to  one  another,  as  well 
as  on  the  E.M.r.  of  the  charging  battery.     In  order 
to  get  great  extent  of  surface,  a  condenser  is  built 
up,   as  in   the  diagram  (Fig.    49),  of  a  very  large 
Fig.  49.      Diagram  to    show   "umber  of  plates  of  tinfoil,  separated  by  discs  of 
the  mode  of  construction  of   mica  or  paraffined    paper.      Alternate  discs    are 
a  condenser.  connected  together  :   thus  1,3,5  are  connected  to 

one  pole,  while  2,  4,  6  are  connected  to  the  other. 
The  rheocord  is  used  to  modify  the  amount  or  strength  of  ciu-rent  flowing 
through  a  preparation.  One  form  of  it  is  represented  in  Fig.  50.  A  constant 
source  of  current  at  B  causes  a  flow  of  electricity  from  a  to  fe  through  a  straight 
wire.  As  the  resistance  of  this  wire  is  the  same  throughout  its  length,  the 
fall  of  potential  from  o  to  &  must  be  constant.  The  nerve,  or  whatever  pre- 
paration that  is  used,  is  connected  with  the  straight  wire  at  two  points,  at  a 
and  at  c,  by  means  of  a  shding  contact  or  rider.  Supposing  that  there  is  an 
electromotive  difference  of  one  volt  between  a  and  b,  it  is  evident  that  if  c  is 
pushed  close  to  b,  the  e.m.f.  acting  on  the  nerve  wiU  be  also  one  volt.  The 
E.M.F.,  however,  may  be  made  as  small  as  we  like  by  sliding  c  nearer  to  a. 
Thus  if  ab  is  one  metre,  and  there  is  a  difference  of  one  volt  between  the  two 
ends,  then  if  c  be  one  centimetre  from  a,  the  e.m.f.  acting  on  the  nerve  will  be 
volt.  Thus  we  alter  the  current  passing  through  the  nerve  by  altering  the 
which  drives  the  current. 

If  a  weak  current  from  a  Daniell's  cell  (or  any  other  form  of 
battery)  be  passed  through  a  muscle  or  any  part  of  its  nerve,  at  the 
make  of  the  current  the  muscle  gives  a  single  sharp  contraction — 
a  muscle-twitch.  In  this  contraction  the  whole  of  the  muscle  fibres 
may  be  involved.  During  the  passage  of  the  current  no  effect  is 
apparently  produced  and  the  muscle  seems  to  be  quiescent,  though 
on  careful  observation  we  may  see  that  there  is  a  state  of  continued 


100 

E.M.F. 


EXCITATION  OF  MUSCLE  215 

contraction  limited  to  the  immediate  neighbourhood  of  the  cathode, 
which  lasts  as  long  as  the  current  is  passing  through  the  muscle,  and 
is  not  propagated  to  the  rest  of  the  muscle.  If  the  current  be  now 
broken,  the  muscle  may  remain  quiescent.  If  however  the  current 
is  above  a  certain  strength,  the  muscle  responds  to  the  break  of  the 
current  with  another  single  rapid  contraction.  With  a  current  of 
moderate  strength  we  may  get  a  contraction  both  at  make  and  break 
of  the  current,  but  the  make-contraction  may  be  stronger  than  the 
break-contraction.  Thus  stimulation  is  caused  by  the  make  and 
break  of  a  constant  current,  the  make-stimulus  being  more  effective 
than  the  break-stimulus.  If  the  duration  of  the  passage  of  the  current 
is  sufficiently  short,  no  contraction  is  produced  at  the  break  of  the 
current,  however  strong  this  may  be.  The  same  phenomenon  of  a 
single  twitch  may  be  evoked  by  the  passage  of  an  induction  shock. 


Fig.  50. 

This  is  the  current  of  momentary  duration  produced  in  the  second 
circuit  of  an  induction-coil  by  the  make  or  break  of  a  constant  current 
in  the  primary.  Using  this  mode  of  stimulus,  it  is  found  that  the 
contraction  on  break  of  the  constant  current  is  much  stronger  than 
that  on  make.  It  must  not  be  imagined,  however,  that  there  is 
any  contradiction  between  this  and  the  fact  that  [the  make  of  a 
constant  current  is  a  stronger  stimulus  than  the  break. 

When  we  put  a  muscle  in  the  secondary  circuit  and  make  a  current 
in  the  primary,  there  is  a  current  of  momentary  duration  induced  in 
the  secondary  ,  so  that  there  is  a  current  made  (md  broken  through  the 
muscle  ;  and  the  same  thing  takes  place  again  when  the  primary  circuit 
is  broken.  It  has  been  shown  that,  when  we  use  currents  of  such 
short  duration,  the  break  stimulus  is  ineffective  ;  so  in  both  cases, 
whether  we  make  or  break  the  current  in  the  primary  circuit,  we  are 
deaUng  with  a  make  stimulus  in  the  muscle.  The  difference  in  the 
efficacy  of  make  and  break  induction  shocks  is  purely  physical,  and 
depends  on  the  fact  that  the  current  induced  in  the  secondary  coil 
on  make  is  of  slower  rise  and  smaller  potential  than  that  produced 
at  break. 


216  PHYSIOLOGY 

In  using  either  of  these  modes  of  stimulation  we  find  that  there 
is  a  certain  intensity  which  the  stimulating  current  must  possess  in 
order  that  any  effect  shall  be  produced.  Any  strength  of  stimulus 
below  this  is  known  as  a  svbminimal  stimulus.  A  minimal  stimulus 
(sometimes  known  as  liminal  or  threshold  stimulus)  is  the  weakest 
stimulus  that  will  produce  any  result,  i.e.  in  muscle,  a  contraction. 

A  maximal  stimulus  is  one  that  produces  the  strongest  contraction  a  muscle 
is  capable  of  under  the  effects  of  a  single  stimulus,  A  svbmaximul  stimulus  is 
any  strength  of  stimulus  between  these  two  extremes. 


SECTION  HI 

THE  MECHANICAL  CHANGES  THAT   A  MUSCLE 
UNDERGOES  WHEN   IT   CONTRACTS 

If  a  skeletal  muscle,  such  as  the  gastrocnemius,  be  stimulated 
either  directly  or  by  the  intermediation  of  its  nerve  by  any  of  the 
means  mentioned  in  the  foregoing  chapter,  it  responds  by  a  single 
short  sharp  contraction,  followed  immediately  by  a  relaxation.  This 
contraction  is  effected  by  a  change  of  form.  The  volume  of  the 
muscle  does  not  alter  in  the  slightest  degree,  but  each  muscle-fibre 
and  the  whole  muscle  become  shorter  and  thicker.  At  the  same  time, 
if  a  weight  be  tied  on  to  the  tendon  of  the  muscle,  the  muscle  during 
contraction  may  raise  the  weight  and  thus  perform  mechanical  work. 
In  order  to  determine  the  time  relations  of  the  simple  muscle  contrac- 
tion or  the  muscle-twitch,  and  to  study  its  conditions,  it  is  necessary 
to  employ  the  graphic  method,  so  as  to  obtain  a  record  of  the  changes 
in  shape  of  the  muscle  during  contraction.  We  may  in  fact  use  the 
graphic  method  either  for  registering  the  changes  in  volume  or  for 
registering  changes  in  tension  of  a  muscle  which  is  prevented  from 
contracting. 

In  order  to  record  the  muscle -twitch  on  the  frog's  gastrocnemius,  the  muscle 
is  excised  together  •with  a  portion  of  the  femur  to  which  it  is  attached,  and  the 
whole  length  of  the  sciatic  nerve  from  its  origin  in  the  spinal  canal  to  its  inser- 
tion into  the  muscle.  The  femur  to  which  the  gastrocnemius  is  attached  is 
clamped  firmly,  and  the  tendo  AchUlis  attached  by  a  thread  to  a  light  lever, 
free  to  move  roimd  an  axis  at  one  end.  The  point  of  this  lever  is  armed  with 
a  bristle  (anything  that  is  stiff  and  pointed  wUl  do),  which  just  touches  the 
blackened  surface  of  a  piece  of  glazed  paper.  This  paper  is  stretched  round 
a  cylinder  (drum)  which  can  be  made  to  rotate  at  any  constant  speed  required. 
If  the  drum  is  mo\'ing,  the  point  of  the  bristle  draws  a  horizontal  white  line 
on  the  smoked  paper. 

If  a  single  induction  shock  be  sent  through  the  nerve  of  the  preparation 
the  lever  is  jerked  up,  falling  again  almost  directly,  and  a  curve  is  drawn  like 
that  shown  in  Fig.  52. 

A  similar  curve  is  obtained  if  the  muscle  be  stimulated  directly. 

In  all  such  graphic  records  we  should  have  also — 

(1)  A  time  record.  This  is  furnished  by  means  of  a  small  electro-magnet, 
armed  with  a  pointed  lever  writing  on  the  smoked  surface.  This  electro-magnet 
(time  marker  or  signal)  is  made  to  vibrate  100  times  a  second  (more  or  less  as 
may  be  reqviired)  by  putting  it  in  a  circmt  which  is  made  and  broken  100  times 
a  second  by  means  of  a  tuning-fork  vibrating  at  that  rate.     The  timing-fork 

217 


218 


PHYSIOLOGY 


is  maintained  in  vibration  in  the  same  way  as  the  Wagner's  hammer  of  an 
induction-coil. 

(2)  A  record  of  the  exact  point  at  which  the  nerve  or  muscle  is  stimulated.  This 
may  be  obtained  in  two  ways  : 

(a)  When  using  the  pendulum  or  trigger  myograph,  in  both  of  which  the 
recording  surface  is  a  smoked  flat  surface  on  a  glass  plate,  thi§  latter  is  so 


Fig.  51.     Arrangement  of  apparatus  for  recording  simple  muscle-twitch. 

arranged  that  it  knocks  over  a  key  as  it  shoots  across,  and  so  breaks  the  primary 
circuit  and  excites  the  nerve  or  muscle  cf  the  preparation.  As  we  know  the 
exact  point  that  the  plate  reaches  when  it  knocks  over  the  key,  we  can  mark 
on  the  contraction  curve  the  exact  moment  at  which  stimulation  took  place. 

(b)  If  we  wish  to  make  and  break  the  primary  circuit  at  will  by  means  of  a 
key,  a  small  electro-magnetic  signal,  interposed  in  the  circuit,  is  arranged  to 
write  on  the  revolving  drum,  and  so  mark  the  point  of  stimulation. 

In  the  figure  (Fig.  52)  the  upper  line  is  the  curve  dra^ai  by  the  lever  of  the 


Fig.  52.     Curve  of  single  muscle-twitch  taken  on  a  rapidly  moving  surface 
(pendulum  myograph).     (Yko.) 


muscle  as  it  contracts  ;  the  small  upright  line  shows  the  point  at  which  the 
muscle  was  stimulated  ;  and  the  second  lino  is  the  tracing  of  the  chronograph, 
every  vibration  representing  jH  of  a  second. 

In  the  pendulum  mj'ograph  (Fig.  53)  a  smoked  glass  plate  is  carried  on  a 
heavy  iron  pendulum.  At  each  side  the  pendulum  is  armed  with  a  catch, 
which  fits  on  to  other  catches  at  the  side  of  the  triangular  box,  from  the  apex 
of  which  the  pendulum  is  suspended.  At  its  lower  part  the  pendulum  carries 
a  projecting  piece  which  can  knock  over  the  '  kick-over '  key  k,  thus  breaking 
a  circuit  in  which  is  included  the  primary  coil  of  an  induction-coil.  The  lever 
attached  to  the  muscle  is  arranged  so  as  to  write  lightly  on  the  glass  plate. 
Everything  being  ready,  and  the  key  K  closed,  the  pendulum  is  raised  to  A,  the 
catch  A  is  then  released,  and  the  pendulum  falls  at  an  ever-accelerating  rate 
and  then  rises  again,  gradually  slowing  off  until  it  is  caught  again  at  B.  As 
it  passes   by  the  key  it   breaks  the  circuit.      A  break  induction   shock  is 


THE  MECHANICAL  CHANGES  OF  MUSCLE  219 

sent  into   the   muscle  or  nerve,   which   contracts,   and   a   curve  is   obtained 
similar  to  that  shown  in  Fig.  62,     Since  the  rate  of  the  penduJum  is  constantly 


Fig.  53.     Simple  form  of  pendulum  myograph. 

varying  throughout  its  course,  it  is  necessary  to  have  a  tuning-fork,  or  time-marker 
actuated  electrically  by  a  tuning-fork,  writing  just  below  the  muscle-lever. 


Fici.  .")4.     Diagram  of  spring  myograph,  or  '  .shooter.' 

In  the  spring  myograph,  other\vise  known  as  flic  trigger  or  shooter  myograph 
(Fig.  54),  a  smoked  glass  plate  is  also  used.  "  The  frame  supporting  the  glass 
))]ate  slides  on  two  horizontal  steel  wires.  To  make  the  instrujiient  ready  for 
use,  the  frame  is  moved  to  one  side,  which  compresses  a  short  spring.     When 


220 


PHYSIOLOGY 


the  catch  holding  it  in  this  position  is  released  by  the  trigger,  the  spring, 
which  only  acts  for  a  short  space,  gives  the  frame  and  the  glass  plate  a  rapid 
horizontal  motion  ;  and  the  momentum  carries  the  glass  plate  through  the 
rest  of  the  distance,  till  stopped  by  the  buffers.  The  velocity  during  this 
time  is  nearly  constant,  as  the  friction  of  the  guides  is  small.  Two  keys 
are  knocked  over  by  pins  on  the  frame  and  break  electric  circuits.  The 
relative  positions  at  which  the  circuits  are  broken  can  be  altered  by  a  con- 
venient adjustment,  A  tuning-fork  vibrating  about  100  per  second  fixed  to  the 
base   of   the  instrument   marks  the   time  ;    its   prongs   are   sprung   apart   by 


CI  — 


Fig.  55.  Blix  apparatus  for  recording  isometric  and  isotonic  curves  synchronically. 
(Miss  Buchanan.)  p,  the  steel  cylindrical  support  with  jointed  steel  arm  to 
bear  the  isotonic  lever  I,  which  consists  of  a  strip  of  bamboo  ^^•ith  an  aluminium 
tip.  t,  the  isometric  lever,  also  of  bamboo,  except  for  a  short  metal  part  t',  in 
which  are  holes  for  fixing  the  muscle.  The  two  wires  from  an  induction  coil  are 
brought,  one  to  X ,  which  is  in  connection  with  the  support  and  hence  with  the  metal 
bar  t',  the  other  to  y,  which  is  insulated  from  the  support  but  connected  by  a 
copper  wire  with  a  thin  piece  of  copper  surrounding  the  isotonic  lever  at  the  point 
where  the  muscle  is  attached  to  it.  CI,  clamp  for  fixing  the  lower  end  of  the 
muscle  when  an  ipometric  curve  is  to  be  taken.  The  axis  of  the  isotonic  lever  is 
at  X,  close  to  which  is  hung  the  weight  of  50  grm. 


a  block  between  their  ends,  and  the  same  action  which  releases  the  glass 
plate  also  frees  the  fork  by  removing  the  block  and  allows  it  to  ^nbrate  ;  a 
writing  style  then  draws  a  sinuous  line  on  the  smoked  surface  of  the  moving 
glass  plate.  A  muscle  lever  with  a  scale-pan  attached  also  forms  part  of  the 
instrument." 

The  record  obtained  in  either  of  these  ways  may,  in  consequence  of  instru- 
mental inertia,  be  a  very  inaccurate  reproduction  of  the  true  events  occxirring 
in  the  muscle  itself.  When  the  muscle  begins  to  contract  it  imparts  a  very  rapid 
movement  to  the  lever,  which  therefore  tends  to  overshoot  the  mark  and  deform 
the  curve.  This  source  of  error  may  be  almost  avoided  by  making  the  lever  as 
light  as  possible,  and  hanging  the  extending  weight  in  close  proximity  to  the 
axle  of  the  lever,  as  shown  in  Fig,  55,     Since  the  energy  of  a  moving  mass  is 

proportional  to  the  square  of   the  velocity  y=-—j,  and   the   tension  due  to 

the  weight  as  well  as  the  velocity  on  contraction  is  directly  proportional  to  the 
distance  of  the  weight  from  the  axis,  it  follows  that  it  is  better  to  load  the 


THE  MECHANICAL  CHANGES  OF  MUSCLE 


221 


muscle  with  40  grams  1  millimetre  from  the  axis  than  with  1  gram  40  millimetres 
from  the  axis,  though  the  tension  put  on  the  muscle  will  be  the  same  in  both  cases. 
In  the  first  case  the  energy  of  the  moxnng  mass  v,ill  be  proportional  to 
40  X  (IP  1   X  (40)- 

i— 1-=  20,  and  in  the  second  to  ^ — '—=  800,  and  it  is  this  energy  which 

2  2 

determines  the  overshooting  of  the  lever  and  the  deformation  of  the  c\irve. 
Since  throughout  the  contraction  the  lever  follows  the  muscle  in  its  movement. 


Fig.  55a.     Myograph  for  optical  registration  of  muscular 
contraction.     (K.  Lucas.) 


the  tension  on  the  muscle  remains  the  same  throughout,  and  the  method  ia 
therefore  known  as  the  isotonic  method. 

In  many  cases  it  is  of  importance  to  be  able  to  record  the  development  of 
the  energy  (i.e.  the  tension)  of  the  active  muscle  apart  from  any  changes  in 
its  length.  For  this  purpose  the  muscle  is  allowed  to  contract  against  a  strong 
spring,  the  movements  of  which  are  magnified  by  means  of  a  very  long  lever. 
Thus  the  shortening  of  the  muscle  is  almost  entirely  prevented,  but  the  in- 
crease in  its  tension  causes  a  minute  but  proportionate  movement  of  the  spring, 
which  is  recorded  by  means  of  the  lever.  Since  in  this  case  the  length  or 
measurement  of  the  muscle  remains  approximately  constant,  while  the  tension 
is  continually  varying  throughout  the  contraction,  it  is  kno\Mi  as  the  isometric 
method.  The  great  magnification  necessary  in  this  method  introduces  serious 
sources  of  error  ;  but  it  seems  that,  if  all  due  precautions  be  taken  to  avoid 
these  errors,  the  isometric  ciurve  differs  very  little  in  form  from  the  isotonic, 
displaying  only  a  somewhat  quicker  development  of  energy  at  the  beginning  of 
contraction.  It  would  probably  be  better  to  eliminate  the  lever  altogether  and 
magnify  the  minute  movements  of  the  spring  by  attaching  to  it  a  small  hingid 
mirror  by  which  a  ray  of  light  is  reflected  through  a  slit  on  to  a  travelling 
photographic  plate.  Since  the  ray  of  light  has  no  inertia,  magnification  of  the 
movements  may  be  carried  to  any  extent  without  increasing  the  instrumental 
deformation  of  the  curve  (Fig.  55a). 


222  PHYSIOLOGY 

A  simple  muscular  contraction  or  twitch,  such  as  that  in  Fig.  52, 
produced  by  a  momentary  stimulus,  consists  of  three  main  phases  : 

(1)  A  phase  during  which  no  apparent  change  takes  place  in  the 
muscle,  or  at  any  rate  none  which  gives  rise  to  any  movement  of  the 
lever.     This  is  called  the  latent  period. 

(2)  A  phase  of  shortening,  or  contraction. 

(3)  A  phase  of  relaxation,  or  return  to  the  original  length. 

The  small  curves  seen  after  the  main  cm've  are  due  to  elastic 
vibrations  of  the  lever,  and  do  not  indicate  any  changes  occurring  in 
the  muscle  itself.  From  the  time-marking  below  the  tracing  we  see 
that  the  latent  period  occupies  about  ^^  second,  the  phase  of 
shortening  y^,  and  the  relaxation  y^o  second. 

Thus  a  single  muscle-twitch  is  completed  in  about  yu  second. 
It  must  be  remembered,  however,  that  this  number  is  only  approxi- 
mate, and  varies  with  the  temperature  of  the  muscle  and  its  condition, 
being  much  longer  in  a  fatigued  muscle.  Moreover,  it  is  almost 
impossible  to  avoid  some  deformation  of  the  curve  due  to  defects  of 
the  recording  instruments  used.  Thus  the  relative  period  during 
which  no  visible  mechanical  changes  are  taking  place  in  the  muscle 
must  always  be  shorter  than  is  apparent  from  a  curve  obtained  by  the 
foregoing  method.  The  elasticity  and  extensibihty  of  the  muscle 
must  prolong  the  latent  period,  since  the  first  effect  of  contraction  of 
any  part  of  the  muscle  will  be  to  stretch  the  adjacent  part,  and  only 
later  to  move  the  tendon  to  which  the  lever  is  attached.  Thus  if  we 
have  a  weight  supported  by  a  rigid  wire,  and  suddenly  pull  the  upper 
end  of  the  wire  so  as  to  raise  the  weight,  the  latter  will  rise  instan- 
taneously. If,  however,  the  weight  be  suspended  by  a  piece  of  elastic, 
it  will  not  follow  the  pull  exactly,  but  will  lag  behind,  the  first  part  of 
the  pull  being  occupied  with  stretching  the  india-rubber,  and  only 
when  this  is  stretched  to  a  certain  degree  will  the  weight  begin  to 
rise.  The  same  retardation  of  the  pull  would  be  observed  if,  instead 
of  india-rubber,  we  used  a  piece  of  living  muscle. 

It  is  possible  to  obviate  this  instrumental  inertia  by  employing 
solely  photographic  methods  for  the  record  and  magnification  of  the 
muscle- twitch.  Thus  in  the  experiments  of  Sanderson  and  Burchthe 
thickening  of  the  muscle  at  the  point  stimulated  was  recorded 
graphically  by  photographing  the  movement  on  a  slit  (Fig.  56), 
behind  which  was  a  moving  sensitive  plate.  Ihus  avoiding  all 
instrumental  inertia,  and  diminishing  the  inertia  of  the  muscle  to  a 
minimum,  the  mechanical  latent  period  was  found  to  be  only  0-0025 
second  (Fig.  57).  This  figure  we  can  take  as  the  average  latent  period 
for  the  skeletal  muscle  of  the  frog  at  the  ordinary  temperature  of  the 
laboratory  (about  16°  C).  We  shall  have  occasion  later  on  to  consider 
the  changes  which  occur  in  the  muscle  between  the  application  of 


THE  MECHANICAL  CHANGES  OF  MUSCLE  223 

the  stimulus  and  the  moment  at  which  the  first  mechanical  change 
makes  its  appearance. 

The  relaxation  of  muscle  is  helped  by  a  moderate  load,  and   in  a 


Fig.  56.  Burdon  Sanderson's  method  for  photographic  record  of  muscle- 
tmtch.  The  exciting  shock  ia  sent  into  the  muscle  by  the  wires 
d  and  d'. 

normal  condition  is  complete.  It  is  not  active — that  is  to  sav,  is  not 
due  to  a  contraction  in  the  transverse  direction — ^but  is  a  passive 
effect  of   extension  and   elastic  rebound.     This   may  be  shown  by 


Fig.  57.  Photographii-  ic.dul  ol  imistlo-t  wittli.  ( B.  Sanuerson.)  The 
upper  curve  is  the  movement  of  the  muscle,  the  middle  curve  the  signal 
showing  the  moment  of  excitation,  and  the  lower  curve  is  that  of  a 
tuning-fork  vibrating  500  times  a  second. 

allowing  a  muscle  to  contract  while  floating  on  mercury.     The  sub- 
sequent lengthening  on  relaxation  is  very  incomplete. 

Even  Nvith  the  most  careful  arrangements  for  securing  isotonicity 
in  the  record  of  the  contraction  there  is  probably  a  certain  amount  of 


224 


PHYSIOLOGY 


over-shoot  of  the  lever  whenever,  aa  at  high  temperatures,  the  con- 
traction is  sufficiently  rapid.  The  effect  of  this  is  that  one  cannot 
assume  the  existence  of  an  actual  pull  on  the  lever  during  the  whole 


Fig.  58.     V.  Kries'   apparatus   for  taking    '  after-loading  '    and  '  arrested 
contraction '  curves. 

time  of  the  ascent  of  the  latter.  We  can  therefore  speak  of  a  period 
during  which  there  is  contractile  stress — that  is  to  say,  when  the  muscle 
is  actually  pulling  on  the  lever,  which  will  occupy  only  a  part  of  the 


AAAAAAAAAAAAAAAAAAATXA 

Fig.  59.     Curves    of    isotonic    and    arrested  contractions  of  an 
\inloaded  muscle.     (Kaisee.)" 

ascent  of  the  curve.  The  duration  of  this  period  of  contractile  stress 
may  be  shown  by  recording  what  is  known  as  '  arrested '  contractions. 
One  mechanism  for  this  purpose  is  shown  in  the  figure  (Fig.  58).  The 
stop  Su  is  used  simply  for  after-loading  the  muscle  so  that  the  weight 
shall  not  act  upon  the  muscle  until  it  begins  to  contract.  The  stop 
So  may  be  regulated  so  that  it  suddenly  checks  the  movement  of  the 
lever  at  any  desired  height  above  the  base  line.     We  may  thus  get  a 


THE  MECHANICAL  CHANGES  OF  MUSCLE  225 

series  of  contractions  such  as  those  shown  in  Fig.  50.  It  will  be  seen 
that  at  the  points  x\  x",  and  x'"  the  muscle  was  still  pulling  on  the 
lever,  and  therefore  held  it  up  against  the  stop.  At  the  point  \  the 
arrested  twitch  returns  rapidly  to  the  base  hne,  showing  that  the 
movement  of  the  lever  in  the  unarrested  curve  above  this  point  was 
due  to  the  inertia  of  the  moving  parts  and  not  to  the  actual  pull  of 
the  muscle. 


PROPAGATION    OF   CONTRACTION.     THE   CONTRACTION 

WAVE 

The  whole  muscle  does  not  as  a  rule  contract  simultaneously. 
When  excited  from  its  nerve  the  contraction  begins  at  the  end-plates 


Fig.  go. 


Diagram  of  arrangement  for  recording  the  contraction  wave  in  a 
curarised  sartorius, 


and  spreads  in  both  directions  through  the  muscle.  The  rate  of 
propagation  of  the  contraction  wave  can  only  be  measured  by  employing 
a  curarised  muscle,  so  as  to  avoid  the  wide  spreading  of  the  excitatorv 
change  by  means  of  the  intra-muscular  nerve-endings.  For  this 
purpose  a  curarised  sartorius  nmscle  is  taken,  stimulated  at  one  end, 
and  the  thickening  of  the  muscle  recorded  by  means  of  two  levers 
placed,  one  near  the  exciting  electrodes  and  the  second  at  the  other 
end  of  the  muscle,  as  shown  in  the  diagram  (Fig.  60).  The  difference 
between  the  latent  periods  of  the  two  curves  represents  the  time  taken 
by  the  contraction  wave  in  travelling  from  a  to  h.  By  measurements 
carried  out  in  this  way  it  is  found  that  the  rate  of  propagation  of  the 
contraction  in  frog's  muscle  is  3  to  4  metres  per  second  ;  in  the  muscle 
of  warm-blooded  animals  it  may  amount  to  G  metres. 

15 


226  PHYSIOLOGY 

The  actual  duration  of  the  shortening  at  any  given  point  is  neces- 
sarily smaller  than  that  of  the  whole  muscle,  and  amounts  in  frog's 
muscle  to  only  0-05-0-09  sec,  about  hah  the  duration  of  the 
contraction  of  a  whole  muscle  of  moderate  length.  The  length  of  the 
wave  is  obtained  by  multiplying  the  rate  of  transmission  by  the 
duration  of  the  wave  at  any  one  point.  It  varies  therefore  in  frog's 
muscle  between  3000  X  -05  (=  150)  and  4000  X  -09  (=  360)  milli- 
metres. Thus  the  muscle  fibres  in  the  frog  are  much  too  short  to 
accommodate  the  whole  length  of  the  wave,  and  the  contraction  of 
the  whole  muscle  must  be  made  up  of  the  summated  effects  of  the 
contraction  wave  as  it  passes  from  point  to  point.  Hence  the  longer 
the  muscle,  the  more  must  the  contraction  be  lengthened  by  the  time 
taken  up  in  propagation  from  one  end  to  another. 

SUMMATION   OF   CONTRACTIONS 

If  a  muscle  or  its  nerve  be  stimulated  twice  in  succession  so  that 
the  second  stimulus  becomes  effective  before  the  state  of  activity  due 
to  the  first  stimulus  has  come  to  an  end,  we  get  a  combination  of  the 


Td 


Fig.  G1.  Muscle  curves  shov  ing  summation  of  stimuli,  r  and  r',  the  points 
at  which  the  stimuli  were  sent  into  the  nerve.  From  the  first  stimulus 
alone  the  curve  a  h  c  would  be  obtained.  From  r'  the  curve  def  is 
obtained.  These  two  curves  are  summated  to  form  the  curve  aghik 
when  both  stimuli  are  sent  in  at  the  interval  r  »'. 

effects  of  the  two  stimuli,  and  the  resulting  contraction  of  the  muscle 
is  as  a  rule  greater  than  that  which  can  be  evoked  by  a  single  stimulus. 
If  the  interval  between  the  two  stimuli  is  so  far  apart  that  the  second 
becomes  effective  just  as  the  contraction  due  to  the  first  has  commenced 
to  die  away,  the  second  contraction  seems  to  start  from  the  point  to 
which  the  muscle  has  been  raised  by  the  first  (Fig.  61).  If  the  second 
stimulus  becomes  effective  at  the  height  of  the  first  contraction,  the 
shortening  of  the  muscle  may  be  almost  doubled.  By  repeating  these 
stimuli  the  contraction  may  be  made  three  or  four  times  as  extensive 
as  that  due  to  a  single  maximal  stimulus.  This  increase  in  height 
due  to  summation  is  best  marked  when  the  muscle  has  to  overcome 
the  resistance  of  a  considerable  load.  If  the  muscle  is  extremely 
lightly  loaded,  the  contraction  evoked  by  a  single  stimulus  may  be 
as  high  as  that  which  can  be  brought  about  by  repeated  stimuli. 
The  phenomenon  of  siunmation  is  due  to  the  fact  that  by  the  first 


THE  MECHANICAL  CHANGES  OF  MUSCLE 


227 


contraction  the  muscle  is,  so  to  speak,  after- loaded  for  the  second. 
The  period  of  contractile  stress  in  a  frog's  gastrocnemius  at  the 
ordinary  temperature  is  only  -03  to  -04  sec.  This  sudden  jerk 
is  applied  through  an  elastic  tissue,  the  muscle  itself,  to  overcoming 
the  inertia  of  the  weight  which  has  to  be  raised.  If  this  latter  is  at 
all  considerable,  the  moving  mechanism  is  obviously  ill-adapted  for 
the  purpose.  The  energy  contained  in  a  rifle  bullet  is  very  large,  but 
firing  a  rifle  bullet  at  a  door  would  not  be  the  best  way  of  shutting 
the  door.  Even  if  the  door  were  made  of  steel  the  bullet  would 
flatten  itself  atrainst  it  and  its  eneruy  would  be  transformed  for  the 


Fig.  62.  Contractions  of  a  frogs  iniiscle.  Two  single  twitches  are  followed 
by  a  tetanus,  whicli  is  almost  twice  as  high  as  a  single  contraction. 
After  two  more  single  twitches,  the  drum  was  made  to  rotate  more 
slowly,  and  single  shocks  employed,  at  the  same  time  as  the  '  after- 
loading  '  w'as  continually  increased.  It  can  be  seen  that  the  curve 
obtained  in  this  way  is  as  high  as  the  original  tetanus.     {V.  Fbey.) 

most  part  into  a  heat,  only  a  small  part  being  utilised  in  moving  the 
mass  of  the  door.  The  contractile  stress  acting  through  the  muscle 
for  a  period  of  -03  sec.  is  only  sufficient  to  impart  a  certain  velocity 
to  the  weight,  and  therefore  to  raise  it  to  a  certain  height.  Before 
the  muscle  has  had  time  to  accomplish  its  maximum  shortening  the 
period  of  contractile  stress  has  passed  away.  That  this  is  the  case  is 
shown  by  the  fact  that  if  the  muscle  be  after-loaded,  so  that  the  lever 
is  raised  to  the  top  of  the  curve  of  a  single  twitch,  application  of  a 
stimulus  will  make  it  shorten  still  more,  and  by  repeated  after-loading 
in  this  fashion  it  is  possible  to  make  the  muscle  raise  a  weight  in 
response  to  a  single  stimulus  to  the  same  height  that  it  would  raise 
the  weight  if  the  stimuli  were  repeated  many  times  (Fig.  62).  In 
summated  contractions  the  apex  of  the  second  contraction  occurs 
rather  sooner  than  would  be  the  case  if  the  second  curve  had  exactly 
the  same  course  as  the  first  curve.  The  latent  period  of  the  second 
twitch  is  also  often  fomid  to  be  shorter  than  that  of  the  first  twitch. 
Both  these  results  might  be  expected  from  what  we  know  of  the 
deforming  effects  of  elasticity  of  the  muscle  on  the  graphic  record  of 
the  mechanical  events  which  occur  in  the  muscle.  If  summation 
is  to  occur  at  all,  the  single  stimuli  must  not  be  applied  in  too  rapid 
succession.  The  smallest  effective  interval  depends  in  any  given 
preparation  on  the  temperature  and  on  the  strength  of  stimulus.    It 


228  PHYSIOLOGY 

differs  also  according  to  the  nature  of  the  tissue  which  is  being  stimu- 
lated, and  will  be  shorter  in  the  case  of  the  frog's  nerve  than  in  the 
case  of  the  frog's  muscle.  The  reason  for  this  we  shall  have  to 
consider  later. 

TETANUS 
If  a  muscle  be  stimulated  so  many  times  in  a  second  {e.g.  with 

the  interrupted  current  of  an  ordinary  induction-coil)  that  it  has  no 

time  to  relax  between  each  stimulus, 
we  get  a  prolonged  steady  contraction, 
which  in  a  loaded  muscle  is  much  stronger 
than  the  maximal  muscle-twitch,  owing 
to  the  summation  of  the  rapidly  follow- 
ing stimuli.  This  condition  is  called 
tetanus. 

The  rapidity  of  stimulation  needed  to 
produce  an  unbroken  tetanus  depends  on 
the  duration  of  a  single  muscle-twitch, 
and  varies  therefore  according  to  the  kind 
and  condition  of  the  muscle.  Thus  the 
rapidity  need  only  be  small  in  the  case 
of  cooled  and  tired  muscles,  or  of  the 
red  muscles  of  the  rabbit  and  tortoise. 
The  rate  varies  from  about  15  in  the 
case  of  red  muscles  to  30  or  40  for 
white    muscles.      For    the    much    more 

highly   differentiated   muscles  of  insects  the   rate   is    probably  very 

much  greater. 


Fig.  G3.  Curves  showing  forma- 
tion of  tetanus  (from  frog's 
gastrocnemius),  a.  Six  sti- 
muli per  sec.  h.  Ten  stimuli 
per  sec.  c.  Thirty  stimuli 
per  sec. 


CHANGES    IN   THE    MUSCLE    ACCOMPANYING    ACTIVITY 
EXTENSIBILITY.     Besides  the  change  of  form,  we  find  changes 
in  the   elasticity  and  extensibility   of   muscle   taking  place  during 
contraction. 

Living  muscle  in  a  perfectly  normal  condition  is  distinguished  by 
its  slight  but  perfect  elasticity  ;  that  is  to  say,  it  is  considerably 
stretched  by  a  slight  force  (in  the  longitudinal  direction),  but  returns 
to  its  original  length  when  the  extending  weight  is  removed.  The 
length  to  which  muscle  is  stretched  is  not  proportional  to  the  weight 
used,  but  any  given  increment  of  weight  gives  rise  to  less  elongation 
the  more  the  muscle  is  already  stretched.  The  accompanying  curves 
show  diagraramatically  the  elongation  of  muscle  as  compared  with  a 
piece  of  india-rubber  when  the  weight  on  it  is  uniformly  increased. 

Dead  muscle  is  less  extensible  and  its  elasticity  is  less  perfect. 
A  given  weight  applied  to  a  dead  muscle  will  not  stretch  it  so  much  as 


THE  MECHANICAL  CHANGES  OF  MUSCLE  229 

when  the  muscle  was  alive,  but  the  dead  muscle  does  not  return  to 
its  original  length  when  the  weight  is  removed. 
A  contracted  muscle,  on  the  other  hand,  is  more  extensible  than  a 


\ 


Fig.  (ji.     Extcn.sibility  of  iiulin-rubbci'  («)  compared  with  that  of  a  frog's 
gastrocnemius  muscle  (6). 

muscle  at  rest.  A  gram  applied  to  a  tetanised  gastrocnemius  will 
cause  greater  lengthening  than  if  it  were  applied  to  the  same  muscle 
at  rest.  At  the  same  time  the  elasticity  is  more  perfect — that  is  to 
say,  when  the  weight  is  removed  the  muscle  returns  more  quickly  to 
its  original  length. 


SECTION  IV 


THE  CONDITIONS   AFFECTING  THE  MECHANICAL 
RESPONSE   OF   A  MUSCLE 

STRENGTH  OF  STIMULUS.  If  a  series  of  single  break-shocks  be 
applied  to  a  muscle  or  nerve  at  intervals  of  not  less  than  five  seconds, 
it  will  be  found  that  beyond  a  certain  distance  of  the  secondary  from 
the  primary  coil  no  effect  at  all  is  produced.  The  shocks 
are  said  to  be  subminimal.  On  pushing  the  secondary 
coil  nearer  the  primary  a  point  will  be  reached  at  which 
a  small  contraction  will  be  observed.  On  then  pushing  in 
the  coil  a  millimetre  at  a  time  the  contraction  wnll  become 
greater  for  the  next  couple  of  centimetres  [e.g.  as  the  coil 
is  moved  from  12  to  10  cm.  distance).  Further  increase 
of  current  by  approximation  of  the  coils  is  without  effect, 
although  the  current  actually  used  may  be  increased  a 
hundred  times  in  moving  the  coil  from  10  to  0.  It  was 
formerly  thought  that  this  limited  gradation  of  the 
muscular  response  according  to  strength  of  stimulus  was 
due  to  a  similar  gradation  in  the  response  of  each  indi- 
vidual muscle  fibre  of  which  the  muscle  is  composed.  It 
seems  more  probable,  however,  that,  when  a  minimum 
or  subminimal  response  is  obtained,  not  all  the  fibres 
making  up  the  muscle  are  contracting.  A  minimal  con- 
traction is  in  fact  a  contraction  in  which  some  fibres  of 
the  whole  muscle  are  stimulated.  A  maximal  contraction 
is  one  in  which  all  the  fibres  are  stimulated.  So  far  as 
o  concerns  each  individual  muscle  fibre  every  contraction 
Fig.  (j-i.  is  a  maximal  contraction.  The  fibre  either  contracts  to 
its  utmost  or  it  does  not  contract  at  all.  The  rule  of 
'  all  or  none  '  which  was  first  enunciated  for  heart-muscle  is  probably 
true  for  every  contractile  element.  The  difference  between  skeletal 
and  heart  muscle  lies  in  the  fact  that  in  the  former  the  excitatory  pro- 
cess does  not  spread  from  one  fibre  to  its  neighbours.  If,  for  instance, 
we  take  a  curarised  sartorius  and  split  its  lower  end,  as  in  Fig.  65, 
the  stimulus  applied  to  a  causes  a  contraction  only  of  the  left-hand 
side  of  the  muscle,  while  a  stimulus  appUed  to  b  is  in  the  same  way 
limited  to  the  right-hand  side.     If  a  piece  of  ventricular  or  auricular 

230 


THE  MECHANICAL  RESPONSE  OF  MUSCLE 


231 


muscle  of  the  frog  or  tortoise  were  treated  in  the  same  way,  a  stimulus 
applied  at  a  would  cause  a  contraction  which  would  travel  across  the 
bridge  at  the  upper  end  and  extend  to  b. 

It  was  shown  by  Gotch  that,  if  each  of  the  three  roots  which  make  up 
the  sciatic  nerve  and  send  fibres  to  the  gastrocnemius  bo  stimulated  in  turn, 
it  is  often  impossible  to  evoke  a  maximal  contraction  of  the  gastrocnemius, 
however  strongly  each  root  bo  stimulated.  Keith  Lucas  has  shown  that  if 
stimuli  in  gradually  increasing  strength  be  applied  to  the  motor  nerve  (containing 
only  seven  to  nine  fibres,)  which  supplies  the  dorso-cutaneus  muscle  of  the  frog, 
the  contraction  of  the  muscle  increases,  not  gradually,  but  by  a  scries  of  steps. 
This  can  only  bo  explained  by  assinning  that  the  smallest  effective  stimulus 


1 1 1 1 

4  - 

3  - 

pj 

2  • 

■ 

so  100  150  200 

Fig.  G6.  Curve  showing  relation  of  height  of  contraction  of  dorso-cutaneus 
muscle  to  strength  of  Btimulus.  Ordinates  =  height  of  contraction  ; 
abscissa  =  strength  of  stimulus.     (K.  Lucas.) 


excites  perhaps  four  out  of  the  seven  nerve  fibres,  those  immediately  in  contact 
with  the  electrodes.  With  increasing  strength  of  current  the  stimxilus  becomes 
effective  for  the  three  fibres  Ijdng  next  to  these,  and  finally  stUl  further  increase 
of  current  may  excite  all  the  fibres  making  up  the  nerve  (Fig.  66). 

LOAD.  The  height  of  contraction  of  a  muscle  diminishes  as  the 
load  is  increased.  This  diminution  in  height  is  at  first  very  sUght 
and  is  not  proportional  to  the  load,  so  that  the  work  done  by  the 
muscle,  which  is  measured  by  the  product  of  the  weight  lifted  and  the 
height  to  which  it  is  raised,  w  X  h,  with  increase  of  weight  rises  at 
first  quickly,  then  more  slowly  to  a  maximum,  and  then,  on  further 
increasing  the  load,  sinks. 

This  will  be  rendered  clearer  by  reference  to  the  diagram  (Fig.  67) 
representing  the  lengths  of  the  resting  and  contracted  muscle  with 
various  loads.  The  lines  ho,  hj,  &c.,  are  the  actual  height  of  contrac- 
tion of  the  muscle  when  loaded  with  weights  of  0,  10,  20  grm.,  &c. 
The  work  in  each  case  is  given  by  hg  X  0,  hj  X  10,  hg  X  20,  hg  X  30, 
&c.     By  inspection  it  will  be  seen  that — 

O.ho  <10.hi    20.h2    30.h3>  40.h4>  SO.hj. 
In  this  case  therefore  the  maximum  of  mechanical  work  is  obtained 


232 


PHYSIOLOGY 


when  the  muscle  is  loaded  with  about  30  grm.  This  increase  of 
work  with  increased  load  shows  that  the  amount  of  external  work 
performed  by  a  muscle  is  not  a  constant  quantity,  nor  one  determined 
solely  by  the  strength  of  stimulus,  but  is  essentially  conditioned  by 
the  tension  under  which  the  muscle  contracts.  The  muscle  is  in  fact 
endowed  with  a  certain  power  of  adaptation,  so  that  it  can  respond 
with  increased  efforts  or  expenditure  of  energy  when  it  has  more  work 
set  it  to  do.  It  might  be  thought  that  the  increased  mechanical 
energy  evolved  under  these  conditions  had  its  origin  at  the  expense 
of  some  other  form  of  energy,  such  as  heat  or  electrical  changes,  but 
it  is  found  that  increased  tension  augments  all  the  processes  of  muscle, 


Fiu.  67.  Curve  showing  the  length  of  a  muscle  under  variouw  loads  in  the 
contracted  condition  B,  and  uncontracted  condition  A.  The  double 
lines  a  h,  &c.,  represent  the  contracted  muscle,  while  the  long  single 
lines  n  c,  &c.,  show  the  length  of  the  inactive  muscle. 


including  chemical  changes  and  the  production  of  heat.  This  excita- 
tory effect  of  tension  on  skeletal  muscle  is  aided  in  all  the  higher 
animals  by  impulses  which  pass  through  the  central  nervous  system, 
the  nature  of  which  we  shall  have  to  discuss  later  on  when  dealing 
with  the  question  of  so-called  "  tendon  reflexes."  The  phenomenon, 
however,  is  common  to  all  forms  of  contractile  tissues,  and  is  indeed 
much  better  marked  in  such  forms  as  the  heart- muscle  and  the 
unstriated  muscular  fibres  of  the  viscera.  One  may  occasionally  find 
that  the  apphcation  of  a  slight  load  to  a  skeletal  muscle  actually 
increases  the  height  of  the  contraction,  especially  if  the  muscle  be 
not  after-loaded.  In  the  heart-muscle  an  increase  of  tension  within 
physiological  limits  causes  invariably  increased  contraction — a  fact 
of  very  great  importance  for  the  physiology  of  compensation  in  heart 
disease.  This  excitatory  influence  affects  not  only  the  strength  of 
contraction  but  also  the  automatic,  rhythmic,  and  conducting  jjower 
of  the  muscle ;  and  in  some  cases,  as  in  the  snail's  heart,  the  rate  of 
beat  is  absolutely  determined  by  the  tension,  the  heart  stopping 
altogether  if  the  tension  be  reduced  to  nothing. 


THE  MECHANICAL  RESPONSE  OF  MUSCLE  233 

TEMPERATURE.  Spealdng  generally,  the  effect  of  warming  a 
muscle  is  to  quicken  all  its  processes.  The  latent  period  becomes 
shorter  and  the  muscle  curve  steeper  and  shorter. 

It  is  vcrj'  often  observed  tliat  the  height  of  contraction  of  the  warmed  muscle 
is  greater  than  that  obtained  at  ordinary  temperatures.  It  seems  that  this 
apparent  increase  in  height  is  really  instninu-ntal  in  origin,  the  quicker-moving 
muscle  jerking  the  lever  beyond  the  real  extent  of  the  contraction.  If  proper 
means  are  taken  to  eliminate  this  overshooting  of  the  lever,  it  is  found  that  the 


Fig.  68.  Isotonic  and  '  anet^t '  curves  of  muscle-twitch :  (1)  unloaded  at 
14°  C. ;  (2)  at  2.5°  C. ;  (3)  at  0°  C. ;  (4)  loaded  at  14°  C.  Note  that  the 
arrest  curves  attain  tlae  same  height  throughout.     (Kaisek.) 


height  of  contraction  is  luialtered  between  5°  and  20°  C,  the  only  change  being 
in  the  time-relations  of  the  curves.  This  is  especially  well  shoAMi  in  the  so-called 
'  arrest '  curves  (Fig.  68). 

If  a  muscle  be  heated  gradually  (-svithout  stimulation)  up  to  about 
45°  C,  it  begins  to  contract  slowly  at  about  34°  C,  and  this  contrac- 
tion reaches  its  maximum  at  45°  C,  at  which  point  the  muscle  has 
entered  into  pronounced  rigor  mortis. 

Cold  has  the  reverse  effect.  The  intra-molecular  processes  which 
lie  at  the  root  of  the  muscular  activity  are  slowed,  so  that  the  latent 
period  and  the  contraction  period  are  prolonged.  The  action  of 
cold  on  the  excitability  of  muscle  is  to  increase  it,  so  that  any  form 
of  stimulus  is  more  effective  at  5°  C.  than  at  25°  C.  Moreover,  when 
maximal  stimuli  are  being  used,  and  the  muscle  is  heavily  loaded,  the 
first  effect  of  the  application  of  cold  may  be  to  increase  the  height  as 
well  as  the  duration  of  contraction,  for  the  same  reason  that  a  gentle 
push  is  more  efficacious  in  closing  a  door  than  would  be  a  heavy  blow 
with  a  hammer.  If,  however,  a  muscle  be  cooled  for  a  short  time  to 
zero  or  a  little  below,  it  loses  its  irritabihty,  which  returns  if  the 
muscle  be  gradually  warmed  again.     Prolonged  exposure  to  severe 


P 


234 


PHYSIOLOGY 


cold  irrevocably  destroys   its  irritability.    Warming  the  muscle  will 
now  simply  bring  about  rigor  mortis. 

FATIGUE.  A  muscle  will  not  go  on  contracting  indefinitely.  If 
it  be  repeatedly  stimulated,  changes  soon  become  apparent  in  the 
curve  of  contraction.  The  latent  period  is  prolonged,  as  well  as  the 
length  of  the  contractions  ;  the  absolute  height  and  work  done  are 
diminished.  At  the  same  time  the  muscle  does  not  return  to  its 
original    length       the    shortening    which    remains   ia    spoken   of    as 


Fig.  69.  Muscle  curves  showing  fatigue  in  consequence  of  repeated  stimu- 
lation. The  first  six  contractions  are  numbered,  and  show  the  initial 
increase  of  the  first  three  contractions.     (Brodie.) 

*  contraction  remainder.^  After  an  initial  rise  during  the  first  few 
contractions,  these  diminish  uniformly  in  height  till  they  are  no 
longer  apparent,  so  that  the  muscle  is  now  said  to  have  lost  its 
irritability. 

At  the  same  time  there  is  a  great  prolongation  of  the  curve, 
occasioned  almost  entirely  by  a  retardation  of  the  relaxation,  so  that 
after  forty  or  fifty  contractions  several  seconds  may  elapse  before  the 
lever  returns  to  the  base  line  (Fig.  69). 

The  fact  that  the  relaxation  part  of  the  muscle  curve  is  affected  by  various 
conditions,  especially  fatigue,  apparently  independently  of  the  contraction  part, 
led  Fick  to  put  forward  a  theory  that  two  distinct  processes  were  concerned  in 
the  response  of  a  muscle  to  excitation,  one  process  causing  the  active  shortening 
and  the  other  the  relaxation.  (It  must  be  noted  that  this  is  not  the  same  as 
saying  that  the  lengthening  is  an  active  process,  a  statement  negatived  by  the 
behaviour  of  a  muscle  when  caused  to  contract  on  mercury. )  He  suggested  that 
the  disintegration  associated  with  activity  might  be  conceived  as  occurring  in  two 
stages :  the  first  resulting  in  the  production  of  sarcolactic  acid  and  the  active 
shortening  of  the  muscle  ;  the  second  in  the  further  conversion  of  the  acid  into 
CO2,  with  a  consequent  relaxation.  A  retardation  of  this  second  phase  would 
cause  the  prolonged  curve  with  '  contraction  remainder  '  observed  in  a  fatigued 
muscle.  The  absence  of  any  appreciable  evolution  of  heat  in  the  conversion  of 
glucose  to  lactic  acid  shows,  however,  that  the  formation  of  lactic  acid  cannot 
account  for  the  whole  of  the  energy  involved  in  the  phase  of  shortening. 

If  left  to  itself,  the  muscle  which  has  been  exhausted  by  repeated 


THE  MECHANICAL  RESPONSE  OF  MUSCLE  235 

stimulation  will  recover.  The  recovery  ia  hastened  by  passing  a 
stream  of  blood.,  or  even  of  salt  .solution,  through  the  blood-vessels 
of  the  muscle.  Recovery  in  a  muscle  outside  the  body  is  never 
complete. 

The  phenomena  of  fatigue  probably  depend  on  two  factors  : 

(1)  The  consumption  of  the  contractile  material  or  the  substances 
available  for  the  supply  of  potential  energy  to  this  material. 

(2)  The  accumulation  of  waste  products  of  contraction.  Among 
these  waste  products  the  lactic  acid  is  probably  of  great  importance. 
Fatigue  may  be  artificially  induced  in  a  muscle  by  '  feeding  '  it  with 
a  dilute  solution  of  lactic  acid,  and  again  removed  by  washing 
out  the  muscle  with  normal  saline  solution  containing  a  small  per- 
centage of  alkali.  After  a  certain  time  the  mere  removal  of  waste 
products  by  means  of  an  artificial  circulation  of  salt  solution  becomes 
inadequate  to  restore  contractile  power  to  the  muscle.  Li  this  case 
the  muscle  can  be  made  to  contract  once  more  by  supplying  it  with 
fresh  food  material,  as  by  the  circulation  of  serum  or  diluted  blood. 

THE    ACTION    OF    SALTS 

The  action  of  sodium  salts  on  muscle  is  of  considerable  interest. 
We  are  accustomed  to  use  a  0-6  per  cent,  solution  of  NaCl  as  a  '  normal 
fluid  '  to  keep  muscle  preparations  moist.  If,  however,  the  solution 
be  made  with  distilled  water,  it  has  a  distinctly  excitatory  effect 
upon  the  muscle,  so  that  single  induction  shocks  may  cause  tetani- 
form  contractions.  The  same  excitatory  effect  is  still  better  marked 
with  solutions  of  NagCOg.  If  a  thin  muscle,  such  as  a  frog's 
sartorius,  be  immersed  in  a  solution  containing  0-5  per  cent.  NaCl, 
0-2  per  cent.  Na.2HP04,  and  0-04:  per  cent.  NagCOg  (Biedermann's 
fluid),  the  muscle  enters  into  a  series  of  frequent  contractions,  so  that 
it  may  wriggle  from  side  to  side,  or  may  even  '  beat '  for  a  time  with 
the  regularity  of  heart-muscle,  though  at  a  much  greater  rate. 

This  excitatory  action  of  sodium  salts  is  neutralised  by  the  addition 
of  traces  of  calcium  salts.  Hence  the  normal  saline  used  in  the  labora- 
tory should  always  be  made  with  tap  water,  containing  calcium  salts. 

Potassium  salts,  although  forming  so  important  a  constituent  of 
the  ash  of  muscle,  act  as  muscle  poisons,  quickly  and  permanently 
destroying  its  irritability.  If  a  muscle  be  transfused  with  normal 
fluids  containing  minute  traces  of  potassium  salts,  it  at  once  shows 
all  the  signs  of  fatigue,  signs  which  may  be  removed  by  washing  out 
the  potassium  salts  by  means  of  0-6  per  cent.  NaCl  solution.  It  is 
possible  that  the  setting  free  of  potassium  salts  may  be  one  of  the 
factors  involved  in  the  development  of  the  normal  fatigue  of  muscle. 


236 


PHYSIOLOGY 


THE    ACTION    OF    DRUGS 
Of  the  drugs  that  have  a  direct  action  on  muscle,  the  most  remark- 
able is  veratrin,  which  causes  ^n  excessive  prolongation  of  a  muscular 


Fig.  70.  a.  Tracing  of  the  contraction  of  a  frog's  sartorius,  poisoned  with 
veratrin,  in  response  to  a  momentary  stimulus.  The  time-marking 
indicates  seconds. 

B.  Tetanic  contraction  of  normal  sartorius  in  response  to  rapidly 
interrupted  stimuli.  (The  duration  of  the  stimulus  is  indicated  by  the 
words  'on'  and  'off.')  It  will  be  noticed  that  the  two  curves  are 
practically  identical.     (Miss  Buchanan.) 

contraction  (produced  by  a   single  stimulus).     Thus  the  '  twitch '  of 

a  muscle  poisoned  with  veratrin  may  last  fifty  or  sixty  seconds,  instead 

of  the  normal  one-tenth  of  a  second  (Fig.  70). 

Barium  salts  Lave  a  similar,  though 

less  marked  effect. 

In  order  to  carry  out  the  poisoning 

with  veratrin,  very  weak  solutions  (1  in 

100,0(X)    or    1    in    1,000,000   of   normal 

saline)   should  be   used  and  the  muscle 

exposed  to  its  action    for   some  hours. 

We  get  then  on  a  single  stimu- 

1         1 Excitation,  j^s    a    rcspouse    lasting    many 

'*^^^AxA^LAJL^J^_A-AX^/_A.^A-.uuLy  Seconds.      sccouds   and  exactly  similar  in 

Fig.  71.    Tracing  of  the  contraction  of  a   height  and  forni   to  a  tetanus 
muscle   poisoned    by  the  injection   of   a      ■,  ,    ■       i  ,       t 
strong  solution  of  veratrin,  showing  the    obtamed  by  discontinuous  stimu- 

^°"H'' f.*l"*''^*i*^i'?  ^"^  *,°T."''''1"^^  P°^°°*   lation.     If  stronger  solutions  be 
mg  of  different  fibres.     (Bibdeemann.)  ^      ,  •  p     i        i 

used,  the  action  oi  the  drug  is 

apt  to  affect  the  fibres  unequally,  so  that  we  may  have  a  sharp  normal 

twitch  preceding  the  prolonged  contraction  (Fig.  71).     If  the  muscle 

be  excited   immediately  after  the  prolonged  contraction  has  passed 

away,  it  responds  with  a  single  .twitch  hke  a  normal  muscle,  but  if 

allowed  to  rest  a  few  minutes,  stimulation  is  again  followed  by  the 

peculiar  long-drawn-out  contraction. 


SECTION  V 
THE  CHEMICAL   CHANGES   IN   MUSCLE 

CHEMICAL  COMPOSITION  OF  VOLUNTARY  MUSCLE 

It  is  impossible  to  speak  with  certainty  about  the  chemical  com- 
position of  any  li\nng  tissue,  since  in  the  act  of  analysis  we  destroy 
the  life  of  the  tissue ;  all  we  can  do  in  most  cases  is  to  find  the  prosi- 
raate  principles  present  in  the  dead  tissue.  But,  by  using  certain 
precautions,  we  may  learn  some  interesting  facts  about  the  chemistry 
of  living  muscle.  Muscle  of  cold-blooded  animals  may  be  cooled 
below  0^  C.  \s-ithout  losing  its  irritability  on  re-warming,  and  therefore 
we  may  say  without  its  life  being  destroyed.  If  the  living  muscle  of 
frogs  be  frozen,  then  minced  with  ice-cold  knives  as  finely  as  possible 
and  pounded  in  a  mortar  with  four  times  its  weight  of  snow  containing 
0*6  per  cent,  of  common  salt,  and  the  mixture  thrown  on  to  a  filter  and 
kept  at  a  little  over  C^  C,  an  opalescent  fluid  filters  through.  The 
filters  soon  get  clogged  and  therefore  must  be  frequently  changed. 
Their  temperature  must  not  be  allowed  to  rise  over  2°  or  3°  C.  This 
fluid  is  called  muscle- plasm  a.  If  its  temperature  be  allowed  to  rise 
to  that  of  the  room,  it  clots,  and  the  clot  soon  contracts,  squeezing 
out  a  serum,  just  as  in  the  case  of  blood- plasma. 

The  muscle-plasma  is  neutral  or  slightly  alkaline.  When  coagula- 
tion takes  place,  however,  it  becomes  distinctly  acid,  and  this  acidity 
has  been  sho\\Ti  to  be  due  to  the  formation  of  sarcolactic  acid  in  the 
process. 

Arguing  chiefly  from  analogy  with  the  blood-plasma,  the  muscle- 
plasma  has  been  said  to  contain  a  body,  myosinogen,  which  is  con- 
verted when  clotting  takes  place  into  myosin. 

The  exact  natiire  of  the  proteins  in  mascle-plasma,  as  well  as  of  the  pro- 
tein constituent  of  the  clot,  which  we  have  called  myosin,  is  still  a  subject  of 
debate.  Kiihne,  to  whom  we  owe  our  first  Sbcquaintance  with  inuscle-plasma, 
described  the  clot  as  consisting  of  mj'osin,  a  globulin,  soluble  in  5  per  cent, 
solutions  of  neutral  salts,  such  as  Xa0  or  MgSo^,  precipitated  by  complete 
saturation  with  MgSo4,  aad  coagulated  on  heating  to  56°  C.  In  the  muscle- 
serum,  obtained  after  separation  of  the  clot,  he  found  three  proteins,  one 
coagulating  at  4.5'  C,  one  he  called  an  albumate  (i.e.  a  derived  albumen),  and 
the  third  coagulating  about  75°  C,  and  apparently  identical  with  serum 
albumen.  Halliburton  extended  these  researches  to  the  muscles  of  warm- 
blooded animals.      He  descrilx-d  four  proteins  as  existing  in  muscle-plasma, 

237 


238  PHYSIOLOGY 

of   which   two,    paramyosinogen   and   myosinogen,   gave   rise   to   the   clot   of 
myosin. 

In  no  case,  however,  is  it  possible  entirely  to  dissolve  up  the  clot  when  once 
formed,  and  it  seems  that  the  so-called  solution  in  dilute  salt  solutions  was 
merely  an  extraction  of  still  soluble  protein  in  the  meshes  of  the  clot.  Von 
Fiirth  has  sho^vn  that  if  the  muscles  of  a  mammal  are  washed  free  of  adherent 
Ij'mph  and  blood,  the  plasma  obtained  by  extraction  with  normal  salt  solution 
contains  only  two  proteins.  These  proteins  are  extremely  unstable,  and  are 
gradually  transformed  on  standing  into  insoluble  protein,  giving  rise  to  a 
precipitate  in  dilute  solutions,  or  forming  a  jelly-like  clot  in  strong  solutions. 
The  properties  of  these  proteins  may  be  summarised  as  follows  : 

(1)  Myosin  (paramj^osinogen  of  Halliburton).  A  globulin,  coagulating  at 
about  47°-50°  C,  precipitated  by  half  satiuation  with  ammonium  sulphate  or 
on  dialj-sis.  Transformed  slowly  in  solution,  rapidly  on  precipitation,  into  an 
insoluble  protein,  myosin  fibrin. 

(2)  Mj'ogen  (myosinogen  of  Halliburton).  A  protein  allied  to  the  albumens 
in  that  it  is  not  precipitated  by  dialysis.  Coagulates  on  heating  at  55°-60°  C. 
It  changes  slowly  into  an  insoluble  protein,  mj^ogen  fibrin,  but  passes  through 
an  intermediate  soluble  stage  called  soluble  myogen  fibrin.  This  latter  body 
coagulates  on  heating  to  40°  C,  being  instantly  converted  at  this  temperature 
into  insoluble  myogen  fibrin.  It  does  not  seem  that  any  ferment  action  is 
associated  with  these  changes,  which  we  may  represent  by  the  following 
schema  : 

Muscle-plasma. 


^  myosin  or  paramyosinogen.  ^  myogen  (myosinogen  of  Halliburton, 

albumate  of  Kiihne). 

1 
Soluble  myogen  fibrin. 

I 
Myosin  fibrin.  Insoluble  myogen  fibrin. 

Muscle  clot. 

Soluble  myogen  fibrin,  which  in  mammalian  muscle-plasma  forms  only  on 
standing,  exists  apparently  preformed  in  frog's  muscle.  Hence  the  instan- 
taneous clotting  of  frog's  muscle-plasma  on  warming  to  40°  C. 

The  residue  left  after  the  expression  of  the  muscle- plasma  consists 
chiefly  of  connective  tissue,  sarcolemma,  and  nuclei,  and  as  such 
contains  gelatin  (or  rather  collagen),  mucin,  nuclein,  and  adherent 
traces  of  the  proteins  of  the  muscle- plasma  itself. 

The  muscle-serum  contains  the  greater  part  of  the  soluble  con- 
stituents of  muscle.     These  are  : 

(a)  Colouring-Matters.  All  red  muscles  contain  a  considerable 
amount  of  ha3moglobin.  In  many,  a  special  pigment,  probably  allied 
to  hcemoglobin,  is  also  present.  This  has  been  named  myohcematin 
(MacMunn). 

(b)  Nitrogenous  Extractives.  Of  these,  the  most  important 
is  creatin  (C4II9N3O2  +  HgO),  which  occurs  to  the  extent  of  0-2  to 
O--*^  ner  cent.     This  substance  is  found  onlv  in  muscular  and  nervous 


THE  CHEMICAL  CHANGES  IN  MUSCLE  239 

tissues.  Its  significance  we  shall  discuss  later  on  when  inquiring  into 
the  history  of  the  proteins  in  the  body. 

Other  nitrogenous  extractives  are  : 

Hypoxanthine  or  sarcine,  xanthine  (both  bodies  alHed  to  uric 
acid),  and  a  trace  of  urea. 

(c)  Non-Nitrogenous  Constituents.    Fats. 

Glycogen.  The  amount  of  this  is  very  variable.  In  the  embryo 
the  muscles  may  contain  large  quantities,  but  in  the  adult  they  contain 
only  from  04  to  1  per  cent. 

Inosit  (CgHigOe  +  2H2O),  or  '  muscle-sugar,'  which  occurs  in 
minute  traces,  is  non-fermentable,  does  not  rotate  polarised  hght,  and 
does  not  reduce  Fehling's  solution.  It  does  not  belong  to  the  group 
of  carbohydrates  at  all,  being  a  derivative  of  benzene. 

Dextrose.  It  is  doubtful  whether  this  is  present  in  fresh  resting 
muscle. 

(d)  Inorganic  Constituents.  Muscle  contains  about  75  per 
cent,  of  water.  The  ash  forms  1  to  1-5  per  cent,  and  consists  chiefly 
of  salts  of  potassimn  and  phosphoric  acid.  There  are  small  traces  of 
calcimn,  magnesium,  chlorine,  and  iron. 

-  RIGOR    MORTIS 

All  muscles,  within  a  short  time  of  their  removal  from  the  body, 
or  if  left  in  the  body  after  general  death,  lose  their  irritability,  and 
tbis  is  succeeded  by  an  event  which  occurs  rather  suddenly,  and  is 
known  as  rigor  mortis.  The  muscle,  which  Avas  before  translucent, 
supple,  extensible,  becomes  more  opaque,  rigid,  and  inextensible,  and 
shortens.  The  shortening  is  not  very  powerful,  and  can  be  prevented 
by  loading  the  muscle  moderately.  Chemical  changes  also  take  place. 
The  muscle,  which  was  previously  alkaline,  becomes  distinctly  acid, 
the  acidity  being  due  to  the  formation  of  sarcolactic  acid.  There  is 
also  production  of  COg  with  evolution  of  heat.  "  1/ 

It  is  generally  believed  that  this  change  is  identical  with  the 
clotting  of  muscle-plasma,  and  that  the  rigidity  as  well  as  the  contrac-. 
tion  of  the  muscle  is  due  to  the  coagulation  of  the  muscle- proteins. 
That  there  is  at  any  rate  a  close  connection  between  the  two  sets  of 
phenomena  is  shown  by  Brodie's  experiments.  This  observer  found 
that,  if  a  living  muscle  be  lightly  loaded  and  then  warmed  very  gradu- 
ally, a  series  of  stages  in  the  heat-contraction  could  be  distinguished 
corresponding  to  the  coagulation  temperatures  of  the  different  proteins 
described  by  von  Flirth  in  muscle-plasma.  It  seems  likely,  however, 
that  the  main  contraction  at  all  events,  that  which  comes  on  sponta- 
neously after  death  or  immediately  on  warming  the  muscle  to  45°  C, 
has  another  component.  In  the  coagulation  of  the  separated  muscle- 
proteins  there  is  no  evidence  of  any  appreciable  formation  of  sarco- 


240  PHYSIOLOGY 

lactic  acid  or  of  COg,  whereas  the  formation  of  these  bodies  seems  to 
bear  an  important  relation  to  the  occurrence  of  rigor.  Thus  after 
severe  muscular  fatigue,  as  in  hunted  animals,  where  there  has  already 
been  a  considerable  formation  of  these  waste  products  of  muscular 
contraction,  rigidity  may  come  on  almost  immediately  after  death. 
If  living  muscle  be  plunged  into  boiling  water,  it  undergoes  instant 
coagulation,  but  no  chemical  change.  The  reaction  of  the  scalded 
muscle,  like  that  of  fresh  muscle,  is  slightly  alkaline  to  litmus.  No 
sarcolactic  acid  or  carbonic  acid  is  produced.  On  the  other  hand,  in 
surviving  muscle,  after  the  cessation  of  the  circulation,  there  is  a 
steady  formation  of  lactic  acid  which  accumulates  in  the  muscle. 
The  actual  coagulation  of  the  muscle -proteins  occurring  in  rigor  is 
^/  largely,  if  not  entirely,  determined  by  the  increasing  acidity  of  the 
muscle  thereby  produced.  In  fact,  it  is  the  production  of  the  acid 
which  causes  the  onset  of  rigor,  and  not  the  rigor  which  causes  a  sudden 
formation  of  acid.  Hence  if  the  accumulation  of  lactic  acid  be  pre- 
vented by  perfusing  the  muscle  with  salt  solutions,  the  onset  of  rigor 
may  be  postponed  indefinitely,  and  the  muscle  may  begin  to  putrefy 
without  having  undergone  rigor. 

The  lactic  acid  formed  in  muscle  (sarcolactic  acid)  is  a  physical  isomer  of 
the  lactic  acid  formed  in  the  fermentation  or  souring  of  milk.  They  both 
have  the  formula  CH3.CH(0H).C00H,  i.e.  they  are  ethylidene  lactic  acids. 
The  lactic  acid  of  fermentation  is  optically  inactive  ;  sarcolactic  acid  rotates 
polarised  light  to  the  right ;  while  a  thkd  isomer  which  is  Isevo-rotatory  is 
produced  by  the  aption  of  various  bacilli  and  vibriones  on  cane  sugar.  J 

THE  CHEMICAL  CHANGES  WHICH  ACCOMPANY  ACTIVITY 
The  principle  of  the  conservation  of  energy  teaches  us  that  the 
energy  of  the  contraction  of  muscle  must  be  derived  from  chemical 
changes,  probably  processes  of  decomposition  and  oxidation,  occurring 
in  the  muscle  itself.  In  seeking  out  the  nature  of  these  changes  three 
methods  are  open  to  us  : 

(1)  We  can  examine  the  changes  in  the  muscle  itself,  avoiding  so 
far  as  possible  reintegrative  changes  by  working  on  excised  muscles. 

(2)  We  can  investigate  the  changes  in  the  medium  surrounding  the 
muscle.  Muscle  may  be  exposed  in  a  vacuum  or  in  a  confined  space 
of  air,  and  its  gaseous  interchanges  during  rest  and  activity  compared. 
Or  we  may  lead  a  current  of  defibrinated  blood  through  excised  muscles, 
and  determine  the  change  in  the  composition  of  the  blood  before  and 
after  passing  through  the  nmscle  under  various  conditions. 

(3)  A  method  which,  although  apparently  complex,  has  rendered 
the  utmost  service  to  the  physiology  of  muscle  is  to  use  the  changes 
in  the  total  metabolism  of  the  animal  during  rest  and  muscular  work 
as  a  clue  to  the  muscular  metabolism  itself.     In  such  a  case  the 


THE  CHEMICAL  CHANGES  IN  MUSCLE  241 

respiratory  exchanges  of  the  animal  are  determined  (viz.  its  oxygen 
intake  and  its  CO2  output),  and  the  urine  and  faeces  are  carefully 
analysed,  in  order  to  judge  of  the  action  of  muscular  work  on  the 
carbon  and  nitrogen  metabohsm  of  the  body. 

By  one  or  other  of  these  methods  it  has  been  found  that  the  main 
products  of  muscular  activity  are  the  same  as  those  which  are  pro- 
duced during  the  death  of  a  muscle,  viz.  sarcolactic  acid  and  carbon 
dioxide.  It  was  shown  long  ago  by  Helraholtz  that  when  a  muscle  was 
tetanised  to  exhaustion,  the  total  amount  of  its  watery  extractives 
diminished,  while  the  amount  of  its  alcoholic  extractives  increased  ; 
and  there  is  no  doubt  that  part  of  this  difference  is  due  to  the  formation 
of  lactic  acid.  The  souring  of  muscle  during  activity  can  be  easily 
demonstrated  by  stimulating  the  muscle  for  some  time  and  then 
crushing  a  fragment  of  the  excised  muscle  on  litmus  paper.  The 
litmus  is  at  once  turned  red.  Or  we  may  inject  a  solution  of  acid 
fuchsin  under  the  skin  of  a  frog,  and  the  next  day  expose  a  sciatic 
nerve  and  stimulate  it  for  fifteen  or  twenty  minutes.  On  skinning  the 
hind-legs  a  difference  in  colour  will  be  at  once  apparent,  the  leg  which, 
has  been  active  being  of  a  deep  rose  colour,  owing  to  the  action  of  the 
acid  on  the  fuchsin. 

Sarcolactic  acid  is  not  present  in  a  free  state  in  muscle,  the  acidity  being, 
like  that  of  \irine,  due  to  the  presence  of  acid  phosphates.  The  sarcolactic 
acid  can  be  extracted  from  the  muscle  by  means  of  alcohol.  It  is  generally 
.separated  in  the  form  of  the  zinc  sarcolactate,  by  boiling  its  partially  purified 
.solution  with  zinc  carbonate.  Its  presence  may  be  tested  for  by  mtans  of 
Uffelmann's  reagent,  which  is  made  by  the  addition  of  ferric  chloride  to  dilute 
carbolic  acid.  The  purple  solution  thus  produced  is  at  once  changed  to  yeUow 
by  the  addition  of  even  traces  of  lactic  acid. 

A  much  more  definite  colour  reaction  for  lactic  acid  has  been  introduced 
by  Hopkins.  The  test,  is  carried  out  in  the  following  way.  About  5  c.c.  of 
strong  sulphuric  acid  are  placed  in  a  test-tube  together  with  one  drop  of  satiu-ated 
solutioii  of  copper  sulphate,  which  serves  to  catalyse  the  oxidation  that  follows. 
To  this  mixture  a  few  drops  of  the  solution  to  be  tested  are  added,  and  the 
whole  well  shaken.  The  te.st-tube  is  now  placed  in  a  beaker  of  boiling  water  for 
«)nf'  or  two  minutes.  The  tube  is  tlien  cooled  under  a  water-tap,  and  two  or 
three  drops  of  a  very  dilute  alcoholic  solution  of  thiophene  (ten  to  twenty  drops 
in  100  c.c.)  are  added  from  a  pipette.  The  tube  is  replaced  in  the  boiling  water 
and  the  contents  iminediately  observed.  If  lactic  acid  is  present  the  tiviid 
rapidly  as.sumcs  a  bright  cherry  red  colour,  which  is  only  permanent  if  the 
tube  be  cooled  the  moment  after  its  appearance. 

We  get  a  similar  formation  of  lactic  acid  in  excised  mammalian 
muscles  which  are  kept  alive  by  an  artificial  circulation.  We  do  not 
know  how  far  the  formation  of  lactic  acid  occurs  under  normal  circum- 
stances in  the  living  body.  At  all  events,  if  lactic  acid  is  produced 
by  the  muscle  in  any  quantity  during  some  phase  of  its  activity  in 
the  normal  animal,  the  greater  part  is  further  transformed  (to  CO.,) 
before  it  leaves  the  body.   If  actual  dyspnoja  is  present  during  muscular 

16 


242  •  PHYSIOLOGY 

exercise,  lactic  acid  is  certainly  formed  and  may  escape  from  the  body. 
Normal  urine  has  been  shown  by  R\'ifel  to  contain  about  3-4  mg. 
of  lactic  acid  per  hour.  In  one  case  the  urine  passed  thirty  minutes 
after  running  one-third  of  a  mile  with  the  production  of  severe  dyspnoea 
contained  454  mg.  of  lactic  acid.  The  lactic  acid  imder  these 
conditions  can  be  shown  also  to  be  increased  in  the  blood.  Thus,  in 
one  experiment,  the  blood  obtained  before  running  contained  12" 5  mg. 
per  100  c.c,  that  obtained  immediately  after  running  one-third 
of  a  mile  contained  70"8  mg.  per  100  c.c.  On  the  other  hand,  the 
examination  of  the  urines  of  competitors  in  a  twenty-four  hours' 
track  walking  race  showed  no  increase  in  the  output  of  lactic  acid 
above  the  normal  4  mg.  per  hour.  The  excretion  of  lactic  acid  was 
also  observed  many  years  ago  by  Araki  in  cases  where  the  oxidation 
processes  of  the  body  were  interfered  with  in  consequence  of  CO 
poisoning. 

The  second  substance,  carbon  dioxide,  is  continually  being  formed 
by  all  living  tissues,  and  is  the  end-product  of  practically  all  the  carbon 
metabohsm  of  the  body.  If  a  muscle  be  hung  up  in  a  confined  space, 
it  will  be  found  to  take  up  oxygen  and  give  off  COg  ;  and  these  inter- 
changes are  quickened  by  causing  the  muscle  to  contract.  It  has 
been  shown  by  Fletcher  that  the  effect  of  activity  is  dependent  on 
the  composition  of  the  gas  surrounding  the  muscle.  If  it  be  hung 
up  in  a  vacuum  or  in  an  atmosphere  of  nitrogen  or  hydrogen,  there 
is  a  slow  evolution  of  COg,  which  is  not  appreciably  quickened  during 
contraction,  and  seems  to  be  conditioned  by  a  gradual  driving  off  of 
CO2  from  the  alkaline  carbonates  in  the  muscle,  as  a  result  of  the 
steady  production  of  lactic  acid  which  precedes  the  onset  of  rigor. 
If,  however,  the  muscle  be  suspended  in  an  atmosphere  of  pure  oxygen, 
the  formation  of  acid  is  diminished  or  abolished  ;  but  now  each  con- 
traction of  the  muscle  is  followed  by  an  increased  evolution  of  carbon 
dioxide. 

We  see  therefore  that,  according  to  the  environment  of  the  muscle, 
its  activity  is  attended  by  the  formation  either  of  lactic  acid  or  of 
carbon  dioxide,  the  latter  substance  being  the  sole  product  if  sufficient 
oxygen  be  supplied  to  the  muscle.  If  the  supply  of  oxygen  be 
inadequate,  both  substances  are  produced,  the  proportion  of  lactic  acid 
varying  according  to  the  relative  inadequacy  of  the  oxygen  supply. 
This  relation  holds  good  both  in  rest  and  activity,  the  effect  of  activity 
being  merely  to  increase  the  chemical  changes  which  are  going  on 
spontaneously  in  the  surviving  resting  muscle. 

It  is  an  interesting  point  to  determine  whether  we  have  here  really 
two  alternative  chemical  mechanisms  for  the  production  of  energy. 
We  know  that  sugar  can  be  utilised  by  muscle  as  a  food  and  source 


i 


THE  CHEMICAL  CHANGES  IN  MUSCLE  243 

of  energy.  It  has  been  suggested  therefore  that,  in  the  absence  of 
oxygen,  the  energy  for  contraction  is  derived  from  a  process  of  dis- 
integration, each  molecule  of  grape  sugar  breaking  down  into  two 
molecules  of  lactic  acid,  thus  : 

CgHiaOe  =  2C3H6O3. 
sugar  lactic  acid 

On  the  other  hand,  in  the  presence  of  sufficient  oxygen  the  sugar  would 
be  entirely  oxidised  with  the  formation  of  CO2  and  water,  thus  : 

CeHi^Oe  +  6O2  =  6CO2  +  6H2O. 
sugar 

The  change  from  sugar  to  lactic  acid  involves,  however,  practically 
no  evolution  of  energy — so  that  in  the  absence  of  oxygen  the  energy 
of  contraction  must  be  derived  from  some  other  source. 

It  seems  more  probable  that  we  are  dealing  here  with  two  stages  of 
one  process,  and  that  in  the  muscle  under  normal  conditions  {i.e.  richly 
supplied  with  oxygen)  the  first  chemical  change  is  one  of  disintegra- 
tion, leading  to  the  formation  of  lactic  acid  (and  probably  other 
substances),  and  that  this  is  followed  by  a  process  of  oxidation,  in 
which  all  the  products  of  the  first  stage  are  converted  into  CO2,  which 
can  be  rapidly  eliminated  from  the  muscle.  If  the  supply  of  oxygen 
is  deficient,  the  products  of  the  first  stage  remain  in  the  muscle,  giving 
rise  to  the  phenomena  of  fatigue,  and  finally  inducing  the  coagulation 
of  the  muscle-proteins  which  determines  rigor  mortis. 

That  lactic  acid  is  a  normal  metabolite,  and  not  simply  the  result 
of  an  alternative  chemical  change  occurring  only  under  abnormal 
conditions,  namely,  want  of  oxygen,  is  indicated  by  the  fact  demon- 
strated by  Hopkins  and  Fletcher,  viz.  that  the  muscle  possesses  in 
itself  a  chemical  mechanism  for  the  removal  of  lactic  acid  when  once 
formed.  These  observers  have  shown  that  if  a  fatigued  muscle  be 
exposed  to  pure  oxygen,  30  per  cent,  of  the  lactic  acid  produced  by 
the  fatigued  muscle  may  disappear  within  two  hours,  and  50  per  cent, 
within  ten  hours.  Thus  even  apart  from  the  circulation,  which  of 
course  would  remove  large  quantities  of  any  lactic  acid  which  might 
be  produced  in  the  muscles,  the  muscles  themselves  can  deal  with  this 
metabolite  locally. 

Since  the  main  products  of  muscular  activity  are  COj  and  lactic 
acid,  and  no  change  has  been  found  to  occur  in  the  creatine  or  other 
nitrogenous  extractives  of  the  muscle  during  contraction,  it  has  been 
thought  that  the  sole  source  of  muscular  energy  is  the  combustion  of 
carbohydrate  or  fatty  material,  the  proteins  of  the  body  taking  no 
part  in  the  process.     In  dealing  with  the  general  metaboUsm  of  the 


244  PHYSIOLOGY 

body,  we  shall  see  that  it  is  impossible  to  draw  any  qualitative  distinc- 
tion between  the  metabolism  which  results  in  muscular  work,  and  the 
metabohsm  of  the  resting  animal.     Thus  the  relative  proportion  of 

CO 
the  CO2  produced  to  the  oxygen  taken  in,  the '  respiratory  quotient '-~, 

O2 

will  vary  according  to  the  food  that  is  being  consumed,  being  unity 
with  carbohydrates,  less  than  unity  with  proteins,  and  still  less  with 
fats.  It  is  found  that  muscular  work  does  not  alter  the  respiratory 
quotient,  i.e.  during  work  the  qualitative  metabolism  of  the  whole 
body  is  the  same  as  during  rest.  We  must  conclude  therefore  that 
the  muscle  derives  its  energy  from  the  combustion  of  all  three  classes 
of  food-stuffs,  although  in  the  absence  of  food  it  will  perform  its  work 
at  the  expense  of  stored-up  fat  or  carbohydrate,  proteins  not  under- 
going any  storage  in  the  body. 

The  absence  of  change  in  the  respiratory  quotient  during  exercise 
shows  moreover  that,  in  a  muscle  under  normal  conditions,  the  two 
processes,  viz.  the  taking  in  of  oxygen  and  the  giving  out  of  COg,  keep 
pace  one  with  the  other.  In  warm-blooded  animals  the  shutting  off 
of  the  oxygen  supply  rapidly  induces  paralysis  and  loss  of  irritability 
of  the  muscles.  This  result,  coupled  with  the  fact  that,  as  mentioned 
above,  the  final  results  of  muscular  activity  differ  according  as  the 
muscle  is  or  is  not  suj)plied  with  oxygen,  suggests  that  the  oxygen 
takes  part  in  the  process  of  activity  only  after  the  disintegration  of  the 
complex  living  molecule  has  already  begun. 

Such  a  conclusion  is,  however,  opposed  to  the  generally  accepted 
views  on  the  nature  of  the  oxidation  j^rocesses  in  the  cell.  According 
to  Hermann,  Pfliiger,  Verworn,  and  others,  there  is  during  rest  a 
building  up  both  of  oxygen  and  food  material  into  the  living  molecule. 
Activity  consists  in  a  rearrangement  of  the  molecule  (spoken  of 
by  Hermann  as  the  inogen  molecule),  with  the  assumption  of  more 
stable  positions  by  the  oxygen  and  carbon  atoms,  and  a  consequent 
Ijroduction  of  COg.  (Compare  the  explosion  of  gun-cotton  or  nitro- 
glycerin.) The  presence  of  this  intramolecular  oxygen  in  an  unstable 
position  would  be  a  necessary  condition  both  for  the  irritability  as 
well  as  for  the  activity  of  all  forms  of  living  tissue,  especially  muscle 
and  nerve. 

If  the  muscle  can  use  all  classes  of  food-stuffs  in  its  metabolism, 
one  would  expect  to  find  some  change  in  the  nitrogenous  constituents 
as  the  result  of  activity.  Physiologists  have  searched  in  vain,  however, 
for  any  evidence  of  the  formation  of  creatin  or  urea  in  excised  muscle 
during  contraction.  Cathcart  and  Brown  have  found  an  insignificant 
increase  of  creatin  in  excised  frog's  muscle  during  contraction  and  a 
more  significant  decrease  if  the  circulation  has  been  maintained  intact 


THE  CHEMICAL  CHANGES  IN  MUSCLE  245 

during  the  stimulation  of  the  muscle.  SchondorfE  has  shown  that  if 
excised  muscle  be  kept  alive  by  perfusion  of  defibrinated  blood,  its 
activity  is  associated  with  slightly  increased  formation  of  ammonia. 
The  formation  of  ammonia  is,  however,  the  natural  mode  of  protection 
of  the  whole  organism  against  acid  poisoning,  and  it  seems  .quite 
probable  that  in  SchondorfE's  experiments  the  ammonia  formation 
was  simply  a  secondary  result  of  the  lactic  acid  formation  and  not  a 
direct  expression  of  the  metabolism  of  the  active  muscle. 


SECTION  VI 

THE  PRODUCTION  OF  HEAT  IN  MUSCLE 

The  experience  of  everyday  life  teaclies  us  that  muscular  exercise 
is  associated  with  increased  production  of  heat.  Thus  a  man  walks 
fast  on  a  frosty  day  to  keep  himself  warm.  In  large  animals  the 
production  of  heat  in  muscular  contraction  can  be  easily  shown  by 
inserting  the  bulb  of  a  thermometer  between  the  thigh  muscles, 
and  stimulating  the  spinal  cord.  The  rise  of  temperature  produced 
in  this  way  may  amount  to  several  degrees.  This  observation  is 
confirmed  when  we  investigate  the  contraction  of  an  isolated  muscle 
outside  the  body.  If  a  frog's  muscle  is  tetanised,  its  tempera- 
ture rises  from  0-14°  to  0'18°  C,  and  for  each  single  twitch  from 
0001°  to  0-005°  C. 

It  is  evident  that  such  small  changes  in  temperatvire  as  0-001°  cannot  be 
estimated    by  ordinary  thermometric  methods.     By  converting  a  heat  change 

into   an   electrical   change,   however,   we   can 
_^°°'-  estimate  differences  of  temperature  with  much 

greater  accuracy  and  fineness  than  b3'  the  use 
of  a  thermometer.      Two  main  principles  are 


Q 


Antimony   B  |  )  employed  in  measuring   temperature  by  elec- 

^y,  trical  methods.    The  thermo-electrical  method 

■i^  depends    on   the   fact    that,    when    the   junc- 

^'^"'^  tions  of  a  circuit  made  of  two  metals  are  at 

Fig.  72.  different  temperatures,  a  current  of  electricity 

generally    flows    through    the    circuit.      This 

current  can  be  measured  by  means  of  a  galvanometer,  and  is  proportional  to 

the  difference  of  temperature  between  the  two  junctions.     Thus  in  the  circuit 

(Fig.  72)  composed  of  two  metals,  antimony  and  bismuth,  if  the  upper  junction 

be  cooled,  there  will  be  a  current  flomng  from  antimony  to  bismuth  in  the 

direction  of  the  arrow,  and  this  cm-rent  wiU  within  limits  be  proportional  to 

the  difference  of  temperature. 

To  measure  the  production  of  heat  during  muscular  contraction,  a  small  flat 
thermopile  (containing  four  or  six  elements  composed  of  iron  and  German 
silver)  is  fi:sed  with  one  of  its  ends  between  two  frog's  gastrocnemii.  Another 
exactly  similar  pile,  but  reversed,  is  placed  between  two  other  gastrocnemii, 
which  are  kept  resting  and  at  a  perfectly  constant  temperatm-e.  So  long  as  the 
two  piles  are  at  the  same  temperature  no  current  flows  ;  but,  with  a  sensitive 
galvanometer,  the  shghtest  difference  of  temperature,  such  as  that  caused  by  the 
contraction  of  one  pair  of  muscles,  at  once  causes  a  deflection  of  the  galvanometer, 
the  extent  and  direction  of  which  enable  us  to  estimate  exactly  the  seat  and 
amount  of  heat  produced. 

When  wc  are  using  such  delicate  detectors  of  temperature  difference,  we  are 

246 


THE  PRODUCTION  OF  HEAT  IN  MUSCLE 


247 


mot  by  the  difficulty  that  every  junction  in  the  circuit  tends  to  become  the 
seat  of  an  electromotive  force  in  consequence  of  slight  changes  of  tempera- 
ture due  to  currents  of  air,  &c.  It  is  therefore  advisable  to  use  a  plan  adopted 
by  Blix,  of  placing  all  the  apparatus,  the  muscle  included.,  within  the  galvano- 
meter case.  The  arrangements  of  such  an  experiment  as  employed  by  A.  V. 
Hill  are  sho^vn  in  the  diagram  (Fig.  73). 

In  this  instrument  the  junction  of  copper  with  the  alloy  constantan 
constitutes  a  tliermo-electric  couple.  Tnc  magnet  and  mirror  chamber  is 
entirely  separated  off  from  the  rest  of  the  instrument  by  the  walls  of  the 
tube  containing  the  magnet.     The  grooves  are  usually  filled  with  plasticine. 


Maanet  &  Mirror  Chamber 


Constantan  Plug 


Groove 

*^  Broca  Magnet 
System 

Copper  Coil 


Electrode 


Celluloid  Plate 


Electrode 


Fig.  73. 


and  into  them  fit  the  edges  of  an  outer  case  of  brass  constituting  the  walls  of 
the  muscle  chamber.  The  inside  of  this  case  is  lined  \\\\\\  wet  blotting-paper. 
The  copper  coil  consists  of  many  more  turns  than  are  shown  in  the  figure  : 
its  ends,  aa  and  bb,  are  separated  by  the  celluloid  plate,  and  are  coimected 
by  the  constantan  plug  ;  the  points  where  the  copper  meets  the  constantan 
constitute  the  thermo-electric  junctions.  The  tube  containing  the  magnet 
hangs  down  through  holes  bored  in  the  broad  copper  coil.  The  two  semi- 
membranosus muscles  ride  astride  of  the  celluloid  plate,  one  in  contact  with  each 
end  of  the  constantan  plug.  The  small  piece  of  bone  at  their  upper  ends  which 
has  been  left  connecting  the  two  muscles  is  placed  exactly  on  the  top  of  the 
celluloid  plate  at  x  and  held  in  position  by  a  clamp  (not  shoAMi  in  the  figure). 
The  copper  terminals  of  the  coil  are  coated  with  celluloid  varnish  to  prevent 
short-circ\iiting  of  the  thermo-electric  currents,  and  to  prevent  poisoning  of 
the  muscles.  Each  muscle  is  in  contact  with  a  pair  of  electrodes,  made  of  fine 
platinum  wire  ;  the  muscle  lies  over  the  upper  and  beneath  the  lower  of  these 
electrodes,  as  shown  in  the  figine.  The  tendons  at  the  lower  emls  of  the  muscles 
are  tied  to  silk  threads  which  pass  through  holes  in  the  base  of  the  iustrunu-nt. 
These  are   then  attached  to  recording  levers  which  write  on  a  drum  l>eneath 


248 


PHYSIOLOGY 


the  table.  When  all  is  ready  three  heavy  soft-iron  cylinders  are  placed  over 
the  instrument :  the  latter  is  screwed  to  a  wooden  block  which  is  fixed  to  a 
thick  iron  plate  attached  to  the  table.  In  the  cylinders  holes  are  bored  to 
admit  and  let  out  after  reflexion  the  light  from  a  Nernst  lamp.  The  lamp, 
which  is  about  three  metres  away,  shines  upon  the  mirror,  and  a  line  in  it,  after 
reflexion,  is  focussed  on  to  the  screen,  which  is  also  three  metres  awaj'.  The 
line  is  brought  on  to  the  scale  by  the  small  field  exerted  by  a  control  magnet 
placed  outside  the  cylinders  at  a  suitable  position  on  the  table  :  its  position 
may  be  read  easily  to  half  a  millimetre,  and  the  movement  due  to  a  twitch 
is  usually  of  the  order  of  80  mm.  These  soft-iron  cylinders  cut  off  entirely 
all  external  magnetism  sufficient  to  cause  harmful  distiu-bances  during  an 
experiment.  They  lower  very  largely  the  strength  of  the  constant  external 
field  in  which  the  magnet  lies,  and  leave  it  chiefly  supported  in  anj'^  position 
by  the  quartz  fibre.     Thus  all  the  movements  set  up  in  the  magnet  by  the 


Fig.  74.     Arrangement  of  apparatus  for  measuring  small  differences  of 
temperature. 

thermo-electric  currents  are  working  against  little  more  than  the  torsion 
of  a  quartz  fibre  only  6  fi  thick.  This  explains  the  great  sensitivity  of  the 
instrument. 

A  second  method  depends  on  the  fact  that  rise  of  temperature  increases  the 
resistance  of  a  wire  to  the  passage  of  an  electric  current.  A  current  detector 
consists  of  a  small  grid  of  fine  platinum  wire  which  is  placed  against  the  muscle 
between  two  muscles.  This  grid  is  then  made  one  limb  of  a  Wheatstone's 
bridge  (Fig.  74).  A  small  current  is  passed  through  the  circuit,  and  the  resistances 
are  so  adjusted  that  no  current  flows  through  the  galvanometer.  Any  alteration 
in  temperature  of  the  grid  will  alter  the  balance  of  the  resistance  and  will  cause 
a  current  to  flow  through  the  galvanometer  in  a  direction  Avhich  will  vary 
according  as  the  resistance  in  the  grid  is  increased  or  diminished.  It  is  possible 
to  calibrate  the  arrangement  so  that  a  deflection  of  the  galvanometer  over  one 
degree  will  correspond  to  a  certain  fraction  of  a  degree  of  difference  in  tem- 
perature of  the  grid.  This  method  is  employed  in  Callenders  recording  thermo- 
meters, and  has  been  made  by  Gamgee  the  basis  of  an  arrangement  for  the 
continuous  record  of  the  temperature  of  the  human  body.  • 

The  discovery  of  exact  means  of  measuring  the  heat  production 
during  contraction  was  naturally  utilised  to  determine  the  relation 
between  the  heat  produced  and  the  work  done  under  varying  con- 
ditions. In  the  nmscle,  as  in  a  steam-engine,  we  have  a  conversion 
of  poteiftial  energy  stored  up  in  carbon  compounds  into  kinetic 
energy,  which  may  appear  as  work  and  heat.      In  the  engine  there 


THE  PRODUCTION  OF  HEAT  IN  MUSCLE 


249 


is  a  definite  ratio  between  work  and  heat.  Only  a  certain  small 
proportion  of  the  total  energy  can  be  utilised  as  work,  the  rest  being 
dissipated  as  heat.  The  exact  proportion  depends  on  the  difference 
of  temperatures  that  is  available  in  the  machine,  and  in  the  best 
engines  at  our  disposal  amounts  to  one-tenth.  If  the  machine  does 
no  work,  the  heat  production  is  increased  by  the  amount  corresponding 
to  the  work.  The  same  is  true  to  a  certain  extent  in  muscle.  If  a 
muscle  be  allowed  to  contract  and  relax  twenty  times  when  loaded 
by  a  weight,  the  total  external  work  done  will  be  nothing.     If.how- 


FiG.  75.  Diagram  of  Pick's  Arbeilaammler  or  muscle  crank, 
a  ?» is  a  counter-balanced  lever,  attached  to  the  muscle  M  at  m.  Wlicn  the 
muscle  contracts,  the  catch  c  carries  round  the  circumference  of  the  wheel  D 
and  so  coils  up  the  weight  w  round  the  axle  of  the  wheel.  When  the  muscle 
relaxes,  if  c,  is  in  the  situation  of  the  dotted  line,  the  weight  pulls  the  wheel 
and  lever  back  to  its  original  position.  If,  however,  c.y  be  applied  to  D,  the 
backward  movement  of  the  wheel  is  prevented,  and  the  muscle  is  extended 
simply  by  the  weight  of  the  lever  ah.  Thus  at  each  contraction  the  weight 
is  drawn  a  little  higher,  and  external  work  is  performed  by  the  muscle. 

ever,  the  weight  be  attached  to  the  axle  of  a  wheel,  which  is  provided 
with  a  catch  so  that  the  weight  can  only  be  drawn  up  (Fig.  75),  and 
the  muscle  be  allowed  to  pull  at  each  contraction  on  the  circum- 
ference of  the  wheel,  at  each  contraction  work  is  done.  It  is  found 
that  in  the  latter  case  the  muscle  is  less  heated  than  in  the  former, 
and  the  difference  is  equivalent  to  the  work  done  in  raising  the  weight. 
But  as  soon  as  we  begin  to  alter  the  work  by  altering  the  weight, 
we  are  at  once  met  by  the  difficulty  that  increased  tension  augments 
all  the  properties  of  the  muscle,  and  with  the  same  stinuilus  both 
work  and  heat  jiroduction  are  raised  by  increasing  the  load.  In 
fact  the  maxinmm  amount  of  heat  is  produced  when  the  muscle 


250  PHYSIOLOGY 

is  made  to  contract  against  a  strong  spring,  so  that  it  cannot  shorten 
at  all  (isometric  contraction). 

In  view  of  the  comparison  of  the  muscle  to  a  heat  engine,  it  becomes 
interesting  to  inquire  into  its  efficiency,  i.e.  the  relation  of  the  work 
to  the  total  energy  expended.  This  amount  is  found  to  vary  within 
very  wide  limits.  In  a  fresh  muscle  the  heat  energy  may  be  twenty- 
five  times  as  great  as  the  work  energy,  but  the  heat  evolved  with 
each  contraction  diminishes  with  fatigue  more  rapidly  than  the  work 
done,  so  that  the  proportion  may  fall  to  as  low  as  three  to  one.  In 
the  intact  animal,  in  the  dog  fed  on  a  pure  flesh  diet,  Pfliiger  has 
calculated  that  the  efficiency  may  be  as  great  as  48  per  cent.  The 
experiments  made  by  Atwater  and  Benedict  on  man  point  to  a 
mechanical  efficiency  of  about  12  to  20  per  cent.  The  efficiency 
of  a  heat  engine  is  determined  by  the  difference  of  absolute  tempera- 
tures obtaining  on  the  two  sides  of  the  machine  ;  and  since  we  cannot 
imagine  even  minutely  localised  changes  of  temperature  in  the  animal 
body  of  more  than  a  few  degrees  Centigrade,  we  must  discard  altogether 
the  analogy  of  the  steam-engine,  and  seek  some  other  explanation  of 
the  mechanism  by  which  the  muscle  is  enabled  to  transmute  the  chemical 
energy  of  its  food  into  work  or  heat.  It  seems  probable  that  the  two 
products,  heat  and  work,  are  simultaneous  and  independent  in  their 
origin,  and  that  any  proportion  between  them,  therefore,  is  accidental. 
The  muscle  is,  in  fact,  not  a  heat  engine,  but  a  chemical  engine. 

This  conclusion  is  borne  out  by  the  observations  of  A.  V.  Hill.  He 
finds  that  the  heat  production  of  a  single  twitch  is  usually  of  very 
short  duration,  i.e.  less  than  O'l  sec,  but  that  it  is  prolonged  by 
depriving  the  muscle  of  oxygen,  and  may  outlast  the  mechanical 
efEect.  No  constant  ratio  is  found  between  work  done  and  heat 
evolved.      The  important  factor  is  the  tension,  as  first  pointed  out 

by  Heidenhaim.     In  an  isometric  muscle  twitch   -—  (i,e. '■ )  is 

•^  H  \  heat  / 

constant  whatever  the  number  of  fibres  contracting,  the  strength 

.      T 
of  contraction,  or  the  initial  resting  tension  on  the  muscle ;  i.e.  — 

H 

is  the  same  for  every  fibre.  The  tension  is  the  measure  of  the  potential 
energy  which  is  thrown  suddenly  into  being  at  the  moment  of  excita- 
tion, and  this  is  proportional  to  the  heat,  and  therefore  to  the  total 
chemical  change  evoked.  On  the  basis  of  these  results,  Hill  suggests 
that  there  are  three  stages  in  the  process  of  muscular  contraction  : 

(i)  The  liberation  of  certain  molecules  following  an  excitation. 

(ii)  The  action  of  these  molecules  on  certain  local  structures,  in 
producing  a  local  tension. 

(iii)  The  removal  or  replacement  of  these  molecules,  under  the 
action  of  oxygen,  with  evolution  of  heat. 


SECTION  VII 
ELECTRICAL  CHANGES    IN   MUSCLE 


^i — b. 


Fig.  76.  Diagram  of  non- 
polarisable  electrode. 
a,  covered  A\ire  ;  b,  amal- 
gamated zinc  rod  ;  c, 
glass  tube  ;  d,  saturated 
ZnSO  solution ;  e,  plug  of 


If  a  current  from  a  battery  be  passed  between  two  plates  of  platinum 
immersed  in  acidulated  water  or  salt  solution,  electrolysis  of  the  water 
takes  place,  bubbles  of  hydrogen  appearing  on  the  positive  plate 
(anode),  and  bubbles  of  oxygen  on  the  negative  plate  (cathode). 
If  now  we  remove  the  battery,  and  connect 
the  two  plates  (electrodes)  by  wires  with  a 
galvanometer,  a  current  passes  through  the 
galvanometer  and  water  in  the  reverse 
direction  to  the  previous  battery  current. 
This  current  is  called  the  polarisation  current, 
and  is  due  to  the  electroTysis  of  the  water 
that  has  taken  place.  The  vessel  in  which 
the  electrodes  are  immersed  has  in  fact 
become  a  galvanic  cell,  the  platinum  covered 
with  oxygen  bubbles  being  the  positive 
element,  and  that  covered  with  hydrogen 
bubbles  the  negative  element.  Exactly  the 
zinc8ulphateclay;7,plug    same   process   of  electrolysis   or   polarisation 

of  normal  .saline  clay.  .    i  i  i  j^      ^^  -l 

takes  place  when  we  pass  currents  through 
the  tissues  of  the  body  by  means  of  metallic  electrodes. 

Hence   before   we   can   study  accurately  the   delicate   electrical 
changes  that  may  occur  normally  in  living  tissues,  it  is  necessary 
to  have  some  form  of  electrodes  in  which  this  polarisation  will  not 
occur.      The    '  non-polarisable  '   elec- 
trodes which  are  most  generally  used 
for  this    purpose    are    made   in   the 
following  way.     A  glass  tube  (Fig.  76) 
is  closed  at  one  end  with  a  plug  of 
kaolin  made  into  a  paste  with  a  satu- 
rated solution  of  zinc  sulphate.     The 
rest    of    the    tube    is    filled  with    a 
similar  solution.      Dipping  into  the 
zinc    sulphate   solution   is  a  rod    of 

pure  'zinc,  amalgamated.      Just    before    use,  a  plug  of  china  clay 
made  with    normal  saline   solution  is  put  on  the  end  of  the  tube. 

251 


Fig. 


U -shaped  non-polarisabic 
electrodes. 


252 


PHYSIOLOGY 


so  as  to  effect  a  connection  between  the  zinc  sulphate  clay  and 
the  nerve  or  muscle  which  it  is  desired  to  stimulate  or  lead 
off.  In  these  electrodes  there  is  no  contact  of  metals  with  fluids 
that  can  produce  dissimilar  ions  {e.g.  hydrogen  or  oxygen)  at  the 
surface  of  contact,  and  hence  they  may  be  regarded  as  practically 
non-polarisable.  A  more  convenient  form  is  that  employed  by  Burdon 
Sanderson,  in  which  the  glass  tube  is  bent  into  a  U  (Fig.  77).  The 
mouth  of  the  tube  is  closed  by  a  smaller  glass  tube  plugged  with  clay, 
and  bearing  a  plug  of  normal  saline  clay. 

In  such  electrodes  the  conduction  of  the  current  through  the 
nerve  or  muscle  to  the  metallic  part  of  the  circuit  may  be  represented 
as  follows  : 


Zn 


50^     CI 


Fig.  78. 


If  a  muscle  such  as  the  sartorius  be  removed  from  the  body,  and 
two  non-polarisable  electrodes  connected  with  a  delicate  galvano- 
meter be  applied  to  two  points  of  its  surface,  there  will  be  a  deflection 
of  the  mirror  attached  to  the  galvanometer,  showing  the  presence 
of  a  current  in  the  muscle  from  the  ends  to  the  middle,  and  in  the 
external  circuit  from  the  middle  (or  equator)  to  the  ends.  It  was 
formerly  thought  that  this  current  was  always  present  in  all  normal 
muscles,  and  it  was  spoken  of  as  the  "  natural  muscle  current  "  ; 
the  muscle  was  said  to  be  made  up  of  a  series  of  electromotive  mole- 
cules, the  equator  of  each  molecule  being  positive  to  the  two  poles 
(du  Bois  Raymond).  It  has  been  conclusively  shown,  however  (by 
Hermann  and  others),  that  this  current  of  resting  muscle  is  not  a 
natural  current  at  all,  but  is  due  to  the  effects  of  injury  in  making 
the  preparation.  The  less  the  preparation  is  injured,  the  smaller 
is  the  current  to  be  obtained  from  it,  and  in  some  contractile  tissues, 
such  as  the  heart,  there  may  be  absolutely  no  current  during 
quiescence. 

Hermann  describes  the  fact  of  the  existence  of  currents  of  rest 
thus  :  "  In  partially  injured  muscles  every  point  of  the  injured  pait 
is  negative  towards  the  points  of  the  uninjured  surface."  Fig.  79 
shows  the  direction  of  the  current  in  a  muscle  with  two  cut 
ends.     When  the  whole  muscle  is  quite  dead,  this  current  of  rest, 


ELECTRICAL  CHANGES  IN  MUSCLE  253 

or  '  demarcation  current  '  (Hermann),  disappears.  The  current  is 
due  to  the  electrical  differences  at  the  junction  of  living  and  dying 
(not  dead)  tissue.  If  the  sartorius  of  the  frog  be  cut  out  and  immersed 
for  twenty-four  hours  in  06  per  cent.  NaCl  solution  made  with 
tap  water  {i.e.  containing  lime),  all  the  injured  fibres  die,  and  the 

uninjured   fibres   are  then   found   to   be 

(7~rT~r~r~v    +    ^n^        iso-electrlc  and  therefore  currentless. 
*■  +  +  *■+    -^    +    ">  \ar\  rj^-^Q  existence  of  this  current  may  be 

/;    demonstrated    without    using     a    galva- 
nometer.     If   the   nerve    of   a   sensitive 
muscle-nerve  preparation   (a,  Fig.  80)  be 
Fig.  79.    Current  of  rest.        allowed  to  fall  on  an  excised  muscle  b, 

so  that  two  points  of  the  nerve  are  in 
contact  with  the  cut  end  and  with  the  surface  of  the  second  muscle 
6,  the  muscle  a  will  contract  each  time  the  nerve  touches  b  so  as  to 
complete  the  circuit. 

"Whatever  be  the  explanation  of  this  current  of  resting  muscle, 
there  is  no  doubt  that  a  very  definite  electrical  change  occurs  in  a 
muscle  when  it  contracts.  To  show  this  change,  we  may  lead  ofi 
two  points,  one  on  the  cut  end  and  one  on  the  surface  of  the  muscle 
of  a  muscle-nerve  preparation,  to  a  galvanometer.  We  shall  then 
obtain  a  deflection  of  the  mirror  of  the  magnet,  due  to  the  current  of 
rest  or  demarcation  current.  If  now  tlie  nerve  be  stimulated  with 
an  interrupted  current  so  as  to  throw  the  muscle  into  a  tetanus,  the 
ray  of  light  from  the  galvanometer  mirror 
swings  back  towards  the  zero  of  the  scale, 
showing  that  the  current  which  was  present 
before  is  diminished.  When  the  excitation 
of  the  nerve  is  discontinued,  the  galvanometer 
indicates  once  more  the  original  current 
of  rest.  This  diminution  of  the  current  of 
rest  during  activity  of  a  muscle  is  spoken  of  I^'k;.  so. 

as  the  '  negative  variation.'  Rhe..,scopic  frog. 

In  carrying  out  this  cxpi-riment  it  is  usual  to  compensate  the  demarcation 
current  by  sending  in  a  small  fraction  of  the  current  from  a  constant  cell. 
The  arrangement  of  the  apparatus  is  represented  in  the  accompanj-ing  dia- 
gram. Two  non-polarisablo  electrodes  np  are  applied  to  the  surface  and 
cross-section  of  a  muscle  m.  These  are  connected  with  the  shunt  of  the 
galvanometer,  one  of  the  wires,  however,  being  cormected  with  a  Pohl's  reverser 
P,  and  this  in  its  turn  with  the  shunt  s.  The  two  end-terminals  of  the 
reverser  are  connected  with  a  rheochord,  through  the  wire  of  whicli  ab  a 
constant  current  is  passing  from  the  Daniell  cell  D.  By  means  of  the  rider  c 
the  fraction  of  current  parsing  through  the  reverser  can  be  modified  to  any 
extent.  Tlie  key  k  being  open,  the  muscle  is  connected  with  the  shunt  and 
galvanometer,    and    the    direction    and    extent    o£    the    swing    noticed.      The 


254 


PHYSIOLOGY 


key  k  is  then  closed,  and  by  means  of  the  reverser  the  ciurent  is  sent  through 
the  galvanometer  in  the  opposite  direction  to  the  demarcation  current,  and  the 
rider  c  shifted  until  the  two  currents  exactly  balance  one  another,  and  the 
needle  of  the  galvanometer  returns  to  zero  of  the  scale.  This  adjustment  is 
first  made,  using  only  yvjtJ)  ^^  ^^^  total  current,  and  then  by  means  of  the 
shunt,  xoTT'  TU'  ^^^  finall}^  the  whole  current  is  thrown  into  the  galvanometer. 
If  this  precaution  be  not  taken,  much  too  large  a  current  may  in  the  first  case 
be  sent  through  the  galvanometer,  to  the  detriment  of  the  instrument. 
If  we  know  the  difference  of  potential  between  the  two  ends  of  the  wire, 

the  proportion  —  will  give  us  the  E.M.F.  of  the  demarcation  cmrent.      The 
ab 

galvanometer  needle  having  by  compensation  been  brought  to  zero,  stimu- 
lation of  the  nerve  at  e  by  interrupted  currents  causes  the  needle  to  swing 
at  once  in  the  opposite  direction  to  the  first  variation.  This  swing  is  the 
measure  of  the  negative  variation  or  current  of  action. 


I^^^Jm  omnia-^^       ^ 


e.c. 


Fig.  81. 


In  order  to  study  the  electrical  changes  accompanying  a  single  muscle 
twitch,  it  is  necessary  to  employ  some  instrument  which  can  react  much  more 
rapidly  than  the  ordinary  galvanometer.  For  this  ptu-pose  we  maj^  employ 
either  the  capillary  electrometer  or  the  string  galvanometer  of  Einthoven. 

The  capillary  electrometer  is  an  instrument  for  recording  and  measuring 
difference  of  potential.  That  is  to  say,  if  connected  with  two  points,  it  measures 
the  force  which  would  make  a  current  flow  between  these  two  points^if  they 
were  connected  by  a  wire.  Its  structure  is  very  simple.  It  consists  of  a 
glass  tube  drawn  out  to  a  fine  capillary  point.  This  tube  with  the  capillary  is 
filled  with  mercury.  The  point  dips  into  a  wide  tube  containing  dilute  sul- 
phuric acid,  at  the  bottom  of  which  is  a  little  mercury.  Two  platinum  wires 
melted  into  the  glass  and  dipping  into  the  mercury  serve  as  terminals. 
When  the  instrument  is  used,  the  meniscus  of  the  mercury  in  the  capillary 
at  its  junction  with  the  acid  is  observed  under  the  microscope,  or  a  magnified 
image  of  it  is  thrown  on  a  screen  with  the  aid  of  the  electric  light.  If  now  the 
capillary  and  acid  be  connected  with  two  points,  it  will  be  observed  that  any 
difference  in   the   potential   of   these   two   points  causes   a   movement  of  the 


ELECTRICAL  CHANGES  IN  MUSCLE 


255 


meniscus.     If    the  point  connected  to  acid  bo  negative  as  compared  witli  tlie 

point   connected  to  mercury  in   capillary,  the 

meniscus    moves    towards   the    point    of    the 

capillary.     If  the  acid  be  positive  as  compared 

with  the  capillary,     the  meniscus  moves  away 

from  the  point.     The  extent  of  the  excursion 

is  proportional  to  the  difference  of  potential. 

Since  the  capillary  electrometer  appears  to  have 

no  latent  period,  and  i?  free  from  instrumental 

vibrations,  it  is  extremely  useful  in   recording 

the  quick  changes  in  potential  occurring  in  the 

diphasic    electrical    changes    that    accompany 

every   contraction-wave    in    the    body.      The 

excursions  lend  themselves  well  to  photography, 

so  that  we  may  obtain  a  graphic   record   of 

every  electrical  variation,  and  thus   determine 

its  extent  and  its  time-relations. 

It  must  be  remembered  that  this  instru- 
ment is  an  electrometer  (measurer  of  difference 
of  potential),  and  not  a  galvanometer  (current 
measurer).  When  the  electrometer  is  connected 
with  two  points  at  different  potential,  no 
current  passes  through  it.  Hence  the  use  of 
non-polarisablo  electrodes  is  not  so  essential  in 
experiments  with  this  instrument  as  when  we 
make  use  of  the  galvanometer. 

In  the  U Arsonval  galvanometer  (Fig.  83) 
the  current  is  sent  through  a  coil  of  fine  wire 
hung  between  the  poles  of  a  permanent  magnet. 

The  same  principle  is  made  use  of  in  the  string  Capillary  electVomVter.    (Bxtrch.) 
galvanometer  of  Einthoven  (Fig.  84).     In  this 

a  very  deUcate  tliread  of  silvered  quartz  or  of  platinum  is  stretched  between  the 
poles  of  a  strong  magnet.     The  poles  of  the  magnet  are  pierced  by  holes  so  that 


Fig.  82. 


P 


the  thread  may  be  illumined  bj'  an  electric  light  from  one  side,  and  from  the 
other  may  be  observed  by  means  of  a  microscope  ;  or  a  magnified  imago  of  the 


256 


PHYSIOLOGY 


thread  may  be  thrown  upon  a  screen.  Whenever  a  current  passes  through  the 
tlu'ead  it  moves  laterally,  and  the  lateral  movement  may  be  photographed  on  a 
moving  photograpliic  screen.  Owing  to  the  extremely  minute  dimensions  of 
the  thread  the  instrument  is  one  of  extreme  delicacy.  It  will  detect  very 
minute  currents  and  will  respond  accurately  to  very  rapid  changes  in  potential. 

If  a  perfectly  uninjured  regular  muscle  (Fig.  85),  such  as  the 
sartorius,  be  stimulated  with  a  single  induction  shock  at  one  end,  x, 


Fig.  85.     Diagram  showing  diphasic  variation  of  unhijured  muscle. 

and  two  points,  a  and  b,  be  led  ofE  to  a  capillary  electrometer,  each 
stimulus  applied  at  x  gives  rise  to  an  excursion  of  the  meniscus 
of  the   electrometer,    known   as   a  '  spike,'  and   shown   in    Fig.  86. 


'  Fig.  86.     A  typical  electrometer  record  from  a  sartorius  muscle  excited  by 
■     a  single  induction  shock.     Time-marking  =  200  D.V.     (Keith  Lucas.) 

Knowing  the  constants  of  the  instrument  used,  we  can  analyse  this 
spike,  and  we  find  that  it  represents  a  diphasic  change.  Our  study 
of  the  mechanical  changes  in  muscle  has  shown  that,  when  the  muscle 
is  stimulated  at  x,  a  contraction  wave  commences  which  travels  down 
the  muscle  through  a  and  b.  The  electrical  investigation  of  the 
muscle  shows  that  excitation  of  x  arouses  an  electrical  change  which 


ELECTRICAL  CHANGES  IN  MUSCLE  257 

also  passes    down  the  muscle  at  the  same  rate  as  the  mechanical 
change  which   it  precedes.     If  we  are  leading  off  from  x  and  a  the 
electrical  change  ensues  immediately  upon  the  stimulus,  i  e    there 
IS  no  latent  period  to  the  electrical  change.     On  leading  off  from 
a  and  h  there  is  a  latent  period  between  the  stimulus  and  the  first 
change,  representing  the  time  taken  for  the  change  to  travel  from 
X  to  a.     When  the  change  reaches  a  this  becomes  the  seat   of  an 
electromotive  force  of  such  a  direction  that  the  current  would  pass  in 
the  outer  circuit  from  h  to    a.     We  may  say,  therefore,  that  a  is 
negative  to  h.     A  fraction  of  a  second  later  the  excitatory  change  has 
passed  on  to  6  and  has  died  away  at  a.     Now  h  is  negative  to  a  * 
and  tlie  current  therefore  passes  in  the  opposite  direction.     Between 
a  and  b,  therefore,  there  is  a  diphasic  current,  the  first  phase  repre- 
senting negativity  of  a   to  6,  and  the    second  phase  representing 
negativity  of   6  to   a.      A    diphasic    change    is    thus    also    a    sign 
of  a  propagated  change.     Every  excitation  of  a  normal  muscle  gives 
rise  to  a  diphasic  variation  of  such  a  direction  that  the  point  stimu- 
ated  first  becomes  negative  to  all  other  points  of  the  muscle,  and 
this     negativity,'  to  use  a  loose  but   convenient   expression,  passes 
as  a  wave  down  the  muscle,  preceding  the  wave  of  contraction  and 
travellmg  at  the  same  rate. 

If  one  leading-off  point  be  injured,  e.g.  at  b,  the  change  accompanv- 
ing  excitation  is  absent  at  that  point.  A  single  stimulus  applied  at^a. 
will  m  this  case  give  only  a  monophasic  variation  in  which  a  is 
relatively  negative  to  b. 

When  we  study  the  time  relation  of  the  electrical  variation  ensuin- 
on  a  single  stimulus,  we  find  that  the  electrical  change  under  the 
electrodes  begins  at  the  moment  that  the  stimulus  is  apphed  It 
takes  about  -0025  sec.  to  attain  its  culminating-point.  At  this 
point  the  mechanical  change  or  contraction  of  the  muscle  begins. 

fJu  T"'  '*f.^""7f  *^f  ^  t^^^  «-^^'ted  portion  of  the  muscle  becomes  'negative  ' 
though  sanctioned  by  long  usage,  is  not  very  exact  and  nmv  give  rise  fo  nuV 
concept.on.  When  we  lead  off  the  terminals  of  a  copper-zinc  Lple  or  celHo 
a  ga  vanometor,  a  current  flows  outside  the  cell  fron^  copper  to  zi'and  n  ide 
the  cell  rom  zmc  to  copper.  In  this  ease  the  zinc  is  said  to  be  elect  t 
pos  tzve  to  the  copper,  and  in  the  same  way  we  must  assume  that  the  exci^^ed 
portion  of  a  muscle  is  really  eleclroposUive  to  the  unexcited  po  tion  ^^f 
therefore,  we  speak  of  any  part  of  a  tissue  being  negative,  we  are  u  h.^  a  o  ' 
ventional  expression  to  indicate  the  dircction%f  "the  curent  in  h^  outer' 
circuit,  and  not  the  electrical  condition  of  the  tissue  itself.      In  o  der  to  ^d 

Zr:^z:^::^^f'^i ''-'''  ^^^-^  "^  ^'^^--p^  ^«  replace  thn^o:' 

expression     negatnc     by  the  more  correct  expres.sion  'electropositive  '  Waller 
conSn  ::         '^"^P'"'^''"-^  «f  ^'-  ^-™  "  -ncative  "  to  indicL  the  oh' t  i  I 
fact  that  tU.       'TJ"'^  oxc^tation.     This  term  also  serves  to  emph..ise  the 

17 


258  PHYSIOLOGY 

These  time-relations  vary  with  the  temperature  of  the  muscle.  We 
have  already  seen  that  the  effect  of  lowering  the  temperature  is  to 
increase  the  latent  period  of  the  contraction.  In  the  same  way  it 
slows  the  rise  of  the  electrical  change  and  the  rate  of  propagation 
of  the  wave  of  electrical  change.  This  is  shown  in  Fig.  8^  -  which 
are  given  the  diphasic  response  of  the  sartorms  first  at  8  C  and 
secondly  at  18°  C.     We  are  therefore  justified  in  regarding  the  electrical 


change  as  an  index  to  the  chemical  changes  evoked  in  the  muscle 
as  the  direct  result  of  the  stimulus.  The  flow  of  material,  which  is 
responsible  for  the  change  in  form  of  each  contractmg  unit,  is  secondary 
to  these  changes.  As  the  result  of  stimulation  a  chemical  change  is 
aroused  at  the  point  of  excitation  and  travels  thence  along  the  muscle 
fibres  at  a  rate  of  about  three  metres  per  second,  ^.e.  the  same  rate 
as  that  of  the  following  wave  of  mechanical  change,  and,  like  this, 
varying  with  the  temperature.  Under  certain  conditions  an  excita- 
tory condition  may  be  propagated  without  the  presence  o  a  visible 
contraction.     Thus,  if  the  middle  third  of  the  sartorms  be  soaked 


ELECTRICAL  CHANGES  IN  MUSCLE 


259 


for  a  time  in  water,  it  passes  into  a  condition  known  as  '  water  rigor,' 
in  which  it  is  incapable  of  contracting,  although  capable  of  trans- 
mitting an  excitation  from  one  end  of  the  muscle  to  the  other. 

The  connection  of  a  diphasic  current  of  action  with  an  excited 
condition  of  the  tissues  passing  as  a  wave  from  one  end  to  the  other 
is  shown  still  more  clearly  on  a  slowly  contracting  tissue,  such  as 
the  ventricle  of  the  frog  or  tortoise.  Fig.  88  a  is  a  photographic  record 
of  the  variation  obtained  from  the  tortoise  ventricle,  which  is  led 


m 

■ 

n 

p 

■ 

1 

m 

m 

w 

■ 

•'u''a^/lififti\ 

jfia^i^ 

,.,,^3, 

■ 

■ 

■ 

y^ 

I 

fin 

m 

^mjgj 

2 

¥ui.  88.  Eluutrumetei'  records  of  llie  electrical  variations  in  a  tortoise 
ventricle,  excited  to  beat  rhythmically  by  single  shocks.  A.  Ventricle 
uninjured.     B.  One  leading  off  spot  injured.     (B.  Sanderson.) 


of^  to  a  capillary  electrometer,  one  (acid)  terminal  being  connected 
with  the  base  of  the  ventricle,  the  other  (mercury)  with  the  apex. 
Each  part  of  the  ventricle  remains  contracted  for  a  period  of  H  to 
2  seconds,  and  then  the  contraction  passes  off,  first  at  the  base  and 
later  at  the  apex.  The  electrical  events  are  an  exact  replica  of  the 
mechanical.  Directly  after  the  stimulus  has  been  applied,  the  base 
becomes  negative  and  the  column  of  mercury  moves  up.  A  moment 
later  the  excitatory  condition  extends  to  the  apex.  There  is  thus  a 
sudden  equalisation  of  potential  between  the  two  terminals,  and 
the  mercury  comes  back  quickly  to  the  base  line.     Here  it  stays  for 


260  PHYSIOLOGY 

IJ  to  2  seconds.  During  this  time  the  whole  heart  is  in  an  excited 
condition.  Both  base  and  apex  are  equally  excited,  and  there  can 
be  no  difference  of  potential  between  them.  The  excitatory  condition 
then  passes  off,  first  at  the  base  and  then  at  the  apex.  There  is  thus 
a  small  period  of  time  in  which  the  apex  is  still  contracted  or  excited 
while  the  base  is  relaxed,  and  the  apex  is  therefore  negative  to  the 
base.  This  terminal  negativity  of  the  apex  is  shown  on  the  photo- 
graph by  the  excursion  of  the  column  of  mercury  away  from  the 
point  of  the  capillary.  If  one  terminal,  e.g.  the  apex,  be  injured,  we 
obtain  quite  a  different  variation,  which  is  shown  in  Fig.  88  B.  It 
is  evident  from  this  figure  that  the  electrical  sign  lasts  practically 
as  long  as  the  mechanical  sign  of  the  excited  state,  and  that  we  are 
not  justified  in  regarding  the  first  spike  of  the  diphasic  variation  as 
indicative  of  an  excitatory  wave  attended  by  an  electrical  change 
which  is  independent  of  the  succeeding  mechanical  change. 


Fig.  89.     Superimposed  photographs  of  the  electrical  variation  of  the 
sartorius  in  response  to  a  single  stimulus.     (Bttbdon  Sanderson.) 

The  only  difference  between  the  electrical  changes  in  this  case 
and  in  that  of  voluntary  muscle  is  that  in  the  latter  all  processes 
are  very  much  quicker,  so  that  as  a  rule  the  point  a  (Fig.  85) 
has  ceased  to  be  negative  before  the  negativity  of  b  has  attained 
its  full  height,  and  there  is  thus  no  prolonged  equipotential  stage. 

Although  in  the  case  of  the  slowly  contracting  ventricle  of  the  tortoise, 
the  record  obtained  of  the  electrical  changes  accompanying  its  contraction  by 
means  of  the  capillary  electrometer  shows  with  great  clearness  the  diphasic 
nature  of  the  variation,  and  therefore  the  wave  character  of  the  electrical 
cliange,  considerable  difficulty  is  experienced  sometimes  in  recognising  that  the 
'  spike  '  record  of  the  electrical  change  in  voluntary  muscle  or  in  nerve  is  also 
due  to  a  diphasic  variation.  In  this  case  the  electrical  change  at  any  spot  lasts 
only  about  tt^  second,  and  there  is  not  a  prolonged  equipotential  period, 
as  in  the  case  of  the  heart.  The  nature  of  the  variation  is,  however,  obvious,  if 
we  compare  the  electrometer  record  of  an  intact  and  therefore  currentless  muscle 
with  that  of  a  muscle  in  which  one  of  the  leading-oflf  points  has  been  injured,  so 
as  to  give  rise  to  a  demarcation  current.  Tlie  tAVO  curves  are  given  in  Fig.  89, 
the  upper  shadowy  tracing  being  that  obtained  from  the  injured  muscle.  It  will 
be  seen  that  the  distinguishing  character  of  an  electrometer  record  of  a  diphasic 
variation  in  tlie  rapidly  contracting  striated  muscle  consists  in  the  fact  that  the 
downstroke  of  the  image  of  the  meniscus  is  as  rapid  as  the  upstroke,  whereas  the 
monopJiasic  variation  of  the  injured  muscle  presents  a  slow  fall  produced  by  the 


ELECTRICAL  CHANGES  IN  MUSCLE 


261 


gradual  leakage  of  the  charge  imparted  to  the  instrument  back  through  the 
electrodes  and  muscle.  When  such  a  record  is  analysed,  we  obtain  a  curve 
similar  to  those  in  Fig.  90,  wliich  represent  the  monophasic  variations  of  a 
sartorius  injured  at  one  end,  under  different  conditions  of  temperature.  A 
similar  curve  to  the  diphasic  variation  can  bo  obtained  by  putting  in  a  current 
of  similar  E.M.F.  from  a  battery,  first  in  one  direction  for  itjhj  second,  and 
then  in  a  reverse  direction  for  another  7,^77  second.  It  must  be  remembered 
that  a  diphasic  variation  does  not  mean  that  one  part  of  a  muscle  changes  from 
normal  in  one  direction,  and  then  swings  back  past  the  normal  in  another  direc- 
tion, but  that  a  cliange  in  one  direction  at  onQ  electrode  dies  away  and  is  succeeded 
by  a  similar  change  in  the  same  direction,  which  also  dies  away,  at  the  second 


Fia.  90.     Monophasic  variations  of  an  injured  sartorius. 
B,  at  8°  C.     (Keith  Lucas.) 


A,  at  18"  C 


electrode  :   that  is  to  say,  a  diphasic  variation  implies  the  progression  of  a  wave 
of  electrical  change  between  the  leading-off  points. 

The  electrical  variation  obtained  by  leading  oi!  a  heart  beating 
normally  is  a  much  more  complex  affair,  and  even  now  physiologists 
are  not  agreed  as  to  its  interpretation.  Gotch  has  suggested  that 
the  complex  character  of  the  variations  obtained  both  from  the 
spontaneously  beating  frog's  heart  as  well  as  from  the  mammalian  heart 
is  due  to  the  twisting  and  alteration  in  direction  of  the  fibres  and 
of  the  course  of  the  contraction  wave  which  have  occurred  in  the 
evolution  of  the  heart  from  a  simple  tube.  The  question  will  1  e 
discussed  more  fully  in  chapter  xiii. 


262  PHYSIOLOGY 

THE  DEMARCATION  CURRENT  OR  CURRENT  OF  INJURY 
According  to  Hermann,  muscle  or  nerve  may  become  negative 
under  two  conditions  :  (1)  During  activity  ;  (2)  when  dying  as  the 
result  of  injury.  It  is  doubtful,  however,  whether  these  two  conditions 
are  really  distinct.  Section  or  injury  of  a  muscle  causes  a  prolonged 
stimulation  of  the  adjacent  parts  of  the  muscle  fibres.  These  parts, 
therefore,  being  excited,  must  be  negative  to  the  unexcited  parts 
which  are  further  away  from  the  seat  of  injury,  so  that  a  demarcation 
current  is  really  an  excitatory  current.  We  thus  come  to  the  con- 
clusion, only  paradoxical  in  terms,  that  the  so-called  currents  of 
rest  are  really  currents  of  action  and  are  due  to  excitation  around 
the  injured  spot.* 

We  shall  see  later,  in  dealing  with  the  electrical  changes  which 
accompany  the  excitatory  state,  that  the  two  conditions  of  injury 
and  of  excitation  are  really  attended  with  similar  molecular  changes 
in  the  muscle  or  the  nerve. 

SECONDARY  CONTRACTION.     RHEOSCOPIC  FROG 

The  negative  variation  of  one  muscle  may  be  used  to  make  another 
contract. 

If  the  nerve  of  the  preparation  a  (in  Fig.  91)  be  laid  so  as  to 
touch  at  two  points  the  cut  end  and  surface 
of  the  muscle  h,  and  the  nerve  of  h  then 
stimulated  with  single  induction  shocks,  every 
contraction  of  h  will  be  attended  by  a  con- 
traction of  a,  excited  by  the  negative  varia- 
tion of  the  current  passing  through  its  nerve 
from  the  point  touching  the  cut  end  to  that 
Rheasrojc'frog.  ^^  contact  with  the  equator  of  h. 

If  the  nerve  of  h  is  tetanised,  a  as  well 
as  h  enters  into  a  continued  contraction.  This  '  secondary  tetanus  ' 
is  of  interest  as  showing  that,  although  the  contractions  of  h  are 
fused,  the  excitatory  process  and  negative  variations  are  still  quite 
distinct. 

*  If  the  demarcation  current  is  really  only  due  to  excitation,  we  should 
expect  to  find  it  weaker  than  the  action  current  obtained  by  exciting  the 
whole  muscle  to  contract.  And  this  is  the  case.  The  E.M.F.  of  the  demar- 
cation current  of  a  sartorius  equals  about  0-05  of  a  Daniell  cell.  The  action 
ciirrent  of  the  same  muscle  may  attain  to  an  E.M.F.  =  0-08  of  a  Daniell  cell 
(Gotch). 


RECTIOX  VTTT 

THE   INTIMATE   NATURE   OF   MUSCULAR 
CONTRACTION 

Experiments  on  the  metabolism  of   the    body   as   a    whole    show 

that  the  energy  of  muscular  work  is  derived  from  the  oxidation  of 

the  food-stuffs.     In  man  the  performance  of  work  involves  an  increase 

of  the  oxidative  processes  of  the  body  with  a  corresponding  evolution 

of  energy,  of  which  four-fifths  will  appear  as  heat  while  one-fifth 

may   be   transformed   into   mechanical   work.     In   this   respect  the 

physiological  mechanisms  for  the  production  of  mechanical  energv 

resemble  the  greater  number  of  the  machines  employed  by  man  for 

the  same  purpose.     In  nearly  all  these  the  prime  source  of  energy 

is  the  oxidation  of  carbon  and  hydrogen  in  the  form  of  coal  or  oil. 

In  the  steam-engine  and  internal-combustion  engine  the  whole  energy 

set  free  by  the  process  of  oxidation  appears  first  as  heat,  and  then  a 

certain  proportion  of  the  heat  is  converted  into  mechanical  work. 

There  is  a  limit  to  the  efficiency  of  such  heat  engines,  depending 

on  the  maximum  differences  of  temperature  available  between  the 

two  sides  of  the  working  part  of  the  machine.     The  efficiency  of  any 

T— T' 
heat  engine  is  expressed   by  the  formula  E  =  — - — ,  where  T  is 

the  highest  temperature  (in  absolute  measurement)  obtained  by 
the  working  substance  and  T'  is  the  lowest  temperature  of  the  same 
substance.  Ordinary  engines  rarely  attain  more  than  half  this  ideal 
efficiency,  but  it  is  evident  that  the  greater  the  difference  of  tem- 
perature available  the  greater  will  be  the  efficiency  of  the  machine. 
Internal-combustion  engines,  such  as  the  gas-engine  or  the  oil-engine, 
therefore  give  a  greater  percentage  of  the  total  energy  of  the  fuel 
out  as  mechanical  energy  than  is  the  case  with  the  steam-engine. 

Engelmann  has  maintained  that  in  muscle  there  is  a  similar 
transformation  of  heat  into  mechanical  energy.  He  has  found  that 
non-living  substances,  which  contain  doubly  refractive  particles  and 
possess  the  property  of  imbibition  {e.g.  catgut)  when  soaked  with 
water,  will  contract  on  heating  and  relax  again  on  cooling.  He 
has  constructed  a  model  in  which  a  thread  of  catgut  in  water, 
surrounded  by  a  platinum  coil,  can  be  made  to  simulate  muscular 
contractions  and  relaxations  by  passing  a  heating  current  through 

263 


264  PHYSIOLOGY 

the  platinum  coil.  He  imagined  that  the  chemical  changes  in  the 
muscle  liberate  heat  and  that  the  effect  of  this  heat  upon  the  doubly 
refractive  particles  is  to  make  them  imbibe  the  surroimding  water 
so  that  they  change  from  an  oval  to  a  spherical  shape.  It  would  be 
impossible,  however,  for  any  large  changes  of  temperature  to  take 
place  in  the  muscle  without  entirely  destroying  its  chemical  character, 
and  with  small  differences  of  temperature  it  would  be  impossible 
to  attain  the  efficiency  of  12  to  20  per  cent,  which  characterises  muscle. 
Under  certain  conditions  we  may  obtain  by  a  machine  almost  the 
entire  energy  of  a  chemical  change.  The  condition  is  that  the  chemical 
change  shall  be  susceptible  of  taking  place  in  a  galvanic  battery. 
We  may  use,  for  instance,  a  series  of  Daniell  cells  to  drive  an  electric 
motor  and  allow  the  motor  to  perform  mechanical  work.  Under 
these  circumstances  we  could  theoretically  obtain  100  per  cent,  of 
the  total  chemical  energy  available,  and  in  conditions  of  practice  the 
efficiency  of  the  machine  may  attain  to  70  or  80  per  cent.  A  similar 
arrangement  might  be  present  in  the  ultimate  contracting  elements 
of  the  muscle  fibre.  The  mechanism  in  the  fibre  must  be  one  which,  ^ 
will  provide  for  a  more  or  less  direct  transformation  of  chemical  ^ 
energy  into  mechanical  energy  without  a  previous  conversion  of 
the  chemical  into  heat  energy.  In  the  living  body,  where  every- 
thing is  in  solution,  all  the  energies  may  be  reduced  to  one  of  two 
kinds,  osmotic  energy  and  surface  energy.  The  contractile  machine 
must  therefore  be  one  which  employs  one  or  other,  or  both,  of  these 
forms  of  energy.  We  may,  with  Macdougall,  regard  the  contractile 
element  as  a  cylindrical  structure  differing  in  its  contents  from  the 
surrounding  sarcoplasm.  When  the  muscle  is  at  rest  the  contents 
of  the  muscle  prism  will  be  in  equilibrium  with  the  surrounding  sarco- 
plasm. We  may  imagine  the  excitatory  process  to  consist  in  a  sudden 
chemical  change,  either  of  disintegration  or  of  oxidation,  occurring 
in  the  contents  of  the  muscle  prism.  As  a  result  there  is  a  production 
of  a  number  of  new  molecules  within  the  muscle  prism  [e.g.  of  an  acid 
.or  of  carbon  dioxide),  which  raises  the  osmotic  pressure  within  the 
prism  and  occasions  a  rapid  inflow  of  water  from  the  sarcoplasm. 
As  a  result  the  pressure  in  the  muscle  prism  rises  and  causes  a  bulging 
of  its  lateral  wall  and  a  shortening  of  the  whole  element.  The  subse- 
quent phase  of  relaxation  may  be  due  either  to  a  secondary  change 
in  the  products  of  oxidation,  leading  to  the  formation  of  a  substance 
to  which  the  walls  of  the  prism  are  freely  permeable,  or  to  the  gradual 
leak  of  the  primary  products  of  oxidation  or  disintegration  into  the 
sarcoplasm.  <  The  substance  or  substances  giving  rise  to  the  osmotic 
differences  which  determine  contraction  may  be  either  products,  such 
as  lactic  acid  and  carbon  dioxide,  which  are  formed  during  contraction, 
or  may  possibly  be  of  the  nature  of  neutral  salts  set  free  from  some 


INTIMATE  NATURE  OF  MUSCULAR  CONTRACTION       265 

condition  of  combination  with  the  proteins  of  the  sarcous  element. 
We  liave  indeed  certain  micro-chemical  evidence  of  the  appearance 
of  potassium  salts  in  the  sarcous  element  during  the  state  of  activity 
of  the  muscle. 

On  the  other  hand,  Bernstein  has  suggested  that  the  changes 
during  muscular  contraction  are  determined  by  alterations  in  surface 
tension.  If  a  little  mercury  be  spilt  on  a  plate  the  particles  form 
globules.  They  are  kept  from  spreading  themselves  out  in  a  thin 
film  under  the  influence  of  gravity  in  consequence  of  the  surface 
tension  of  the  mercury.  Any  modification  of  the  surface  will  alter  the 
tension,  and  therefore  state  of  expansion,  of  the  globule.  Thus,  if 
the  globule  be  in  sulphuric  acid  it  undergoes  a  certain  amount  of 
polarisation,  and  becomes  positively  charged.  By  altering  the  charge 
of  such  a  globule  we  can  change  its  shape,  as  is  shown  diagram- 
matically  in  Fig.  92.     If  b  represents  the  shape  of  the  globule  lying 

ABC 


Fit;.  92. 

on  the  plate  in  some  weak  sulphuric  acid,  a  will  represent  the  shape 
of  the  globule  when  it  is  connected  with  the  negative  pole  of  a  battery, 
while  c  will  represent  its  shape  when  it  is  connected  with  the  positive 
pole  of  a  battery,  the  other  pole  in  each  case  being  connected  with 
the  acid.  If  we  consider  muscle  as  made  up  of  a  series  of  chains 
of  oval  particles,  a  chemical  change  in  the  surface  of  these  particles, 
causing  an  increase  of  surface  tension,  will  tend  to  make  them 
assume  the  globular  shape,  and  will  therefore  cause  a  shortening 
and  thickening  of  the  whole  fibre. 

According  to  Schafer,  contraction  is  associated  with  a  flow  of 
the  outer  hyaline  contents  of  the  sarcous  element  into  the  tubular 
structure  forming  the  middle  portion.  Such  a  flow  may  be  deter- 
mined either  by  osmotic  differences  between  the  centre  and  periphery 
of  the  sarcous  element,  or  by  a  change  in  the  surface  tension  obtaining 
between  the  isotropic  fluid  at  the  ends  and  the  anisotropic  structures 
in  the  centre  of  the  muscle  prism. 

It  is  impossible  at  present  to  decide  between  these  different 
theories.  They  have  their  use,  however,  in  showing  the  possibility 
of  '  explaining  '  a  muscular  contraction,  i.e.  of  bringing  it  into  a 
series  of  phenomena  the  other  members  of  which  are  already  familiar 
to  us.  They  may  therefore  serve  to  point  the  direction  which  future 
researches  into  the  intimate  nature  of  muscular  contraction  nmst  take. 


SECTION  IX 

VOLUNTARY  CONTRACTION 

The  whole  of  our  ^analysis  'of  the  processes  accompanying  the 
contraction  of  a  skeletal  muscle  has  so  far  had  reference  merely  to 
the  contractions  evoked  by  artificial  stimuli,  mainly  electric.  These 
contractions  have  either  been  the  simple  twitch,  with  a  duration  of 
about  one-tenth  of  a  second,  evoked  by  a  momentary  stimulus,  or 
the  tetanus,  a  continued  contraction  composed  of  a  number  of  single 
twitches,  summated  and  fused  together.  Under  normal  circum- 
stances the  contraction  of  skeletal  muscles  is  brought  about  either 
reflexly,  or  in  response  to  some  stimulus  descending  from  the  cerebral 
cortex,  the  so-called  '  voluntary  contraction.'  These  contractions 
may  have  a  duration  of  almost  any  extent.  The  quickest  contractions 
carried  out  by  man  have  a  duration  of  about  O'l  sec.  Considerable 
effort  and  training  are  required  to  reduce  a  muscular  movement 
to  this  degree,  and  nearly  all  contractions,  even  the  rapid  ones, 
last  considerably  over  0"1  sec.  Since  we  have  no  certain  means 
of  producing  contractions  of  any  given  length,  except  by  means  of 
repeated  stimuli,  it  is  natural  that  physiologists  have  regarded 
voluntary  contractions  as  similar  to  the  artificial  tetanus,  and  as,  like 
this,  composed  of  fused  single  contractions,  and  have  endeavoured 
to  determine  the  number  of  contractions  per  second,  i.e.  the  natural 
rh37thm  of  the  tetanus.  If,  however,  every  muscular  contraction 
in  the  body  is  to  be  regarded  as  of  the  nature  of  a  tetanus,  effected 
by  rapidly  repeating  stimuli  sent  down  the  motor  nerve  from  the 
central  nervous  system,  we  must  assume  a  similar  discontinuity  for 
the  process  underlying  the  normal  tone  of  muscles,  and  for  the  con- 
tinued contraction  of  unstriated  muscles,  e.g.  of  the  arteries.  Is 
this  discontinuity  of  muscles  really  essential  for  the  production  of  a 
prolonged  contraction  ?  So  far  as  our  present  knowledge  of  the 
intimate  nature  of  muscular  contraction  goes,  it  would  seem  quite 
possible  that  the  continuous  state  of  contraction  is  dependent  on  a 
continuous  evolution  of  energy  in  the  muscle.  We  have  seen  reason 
to  regard  the  chemical  processes  in  a  contracting  muscle  as  presenting 
two  phases,  namely,  (1)  the  production  of  a  substance  which  increases 
the  osmotic  pressure  within  the  sarcous  elements,  or  raises  the  surface 
tension   of  the   ultimate  contractile   elements  of  the   muscle,   thus 

266 


VOLUNTARY  CONTRACTION  267 

causing  a  shortening  and  thickening  of  those  elements  ;  and  (2)  the 
further  change  of  this  substance  into  one  which  can  escape  by 
diffusion,  or  into  a  substance  with  a  low  surface  tension,  so  that 
now  the  muscle  relaxes  and  can  be  stretched  by  any  extending 
force.  If  these  two  phases  went  on  continuously,  but  the  first  phase 
kept  ahead  of  the  second  one,  a  continuous  state  of  contraction 
would  be  produced  in  the  muscle.  Since  the  contraction  of  the 
muscle  only  occurs  in  response  to  impulses  from  the  central  nervous 
system,  we  should  have  to  imagine  also  a  continuous  stream,  e.g.  of 
negatively  charged  ions,  descending  the  nerve  and  evoking  an 
excitatory  change  in  the  muscle-fibres  as  they  impinge  on  the  neuro- 
muscular junction.     We  have  evidence  that   a  state   of  excitation 


lJ^J^Jw^^^^.-, 


I'lG.  93.     Continued   contraction  followed  by  rhythmic  contractions  of  a 
muscle  in  response  to  a  constant  stimulus.     (Biedekma^'n.) 

The  muscle  was  excited  by  the  passage  of  a  constant  current,  the 
cathodal  end  having  been  moistened  with  a  Aveak  solution  of  Na.,CO:;. 

of  a  nerve,  which  is  apparently  continuous,  may  excite  a  corre- 
spondingly continuous  state  of  excitation  in  the  muscle  attached. 
During  the  passage  of  a  constant  current  through  muscle  there  is 
a  continuous  contraction  in  the  neighbourhood  of  the  cathode. 
If  the  irritabiUty  of  the  muscle  at  this  point  be  increased  by 
the  application  of  a  solution  of  sodium  carbonate,  Biedermann 
has  shown  that  this  excitation  is  propagated  to  the  rest  of  the 
muscle,  and  on  closure  of  the  current  we  obtain  a  prolonged 
contraction  followed  by  rhythmic  contractions  (Fig.  93).  More- 
over in  frogs,  the  excitability  of  which  has  been  heightened  by 
keeping  them  at  2°  to  3°  C.  for  some  days,  the  closure  of  a 
descending  current  through  the  sciatic  nerve  causes  a  prolonged 
contraction  of  the  gastrocnemius  ;  and  in  the  same  way  there  may  be 
a  prolonged  contraction  produced  by  the  opening  of  an  ascending 
current  through  the  nerve. 

The  question  however  can  only  be  decided  by  experiment.  If 
a  voluntary  or  reflex  contraction  is  of  the  nature  of  a  tetanus,  we 
should  be  able,  by  a  study  of  the  mechanical  and  electrical  phenomena 
combining  the  contraction,  to  obtain  distinct  evidence  of  this 
causation.  It  was  shown  by  Wollaston  that,  on  listening  to  a 
contracting  muscle,  a  low  sound  was  heard,  which,  according  to  him, 


268  PHYSIOLOGY 

corresponded  to  a  vibration  frequency  of  36  to  40  per  second.  The 
same  observation  was  made  by  Helmholtz,  and  can  be  repeated  by  any 
one  who  will  place  the  end  of  a  stethoscope  on  a  muscle,  e.g.  the 
biceps,  and  listen  to  the  sound  produced  when  it  contracts.  Helm- 
holtz  pointed  out,  however,  that  the  tone  heard  corresponded  to  the 
resonance  tone  of  the  external  ear,  and  was  the  same  as  that  noted 
when  listening  to  any  irregular  sound  of  low  intensity.  Thus  the 
roar  of  London  that  we  hear  in  the  middle  of  Hyde  Park  has  the 
same  pitch  as  the  muscle  sound  of  the  contracting  biceps.  The 
muscle  sound,  therefore,  teaches  us  nothing  as  to  the  pitch  or  number 
of  contractions  per  second  making  up  the  voluntary  tetanus.  It 
merely  points  to  an  irregularity  or  discontinuity  in  this  contraction. 
By  bringing  vibrating  reeds  of  different  frequency  in  contact  with 
the  contracting  muscles  of  the  frog,  Helmholtz  came  to  the  conclusion 
that  the  chief  element  in  the  muscle  sound  was  the  first  over-tone 
of  a  sound  with  a  vibration  frequency  of  18  to  20  per  second,  which, 
according  to  him,  was  to  be  taken  as  representing  the  number  of 
single  contractions  in  every  voluntary  muscular  contraction. 

Nearly  all  voluntary  contractions  present  a  certain  degree  of 
irregularity,  and  the  same  irregularities  are  observed  when  a  tetanic 
spasm  in  the  muscles  of  the  body  is  caused  by  strong  excitation 
of  the  cerebral  cortex,  as  in  epilepsy.  On  taking  a  record  of  such 
contractions,  Schaefer  and  Horsley  showed  that  in  nearly  all  cases 
the  tracing  presents  superposed  undulations  repeated  at  the  rate 
of  eight  to  twelve  per  second.  These  observers  concluded  that  this  / 
was  the  normal  rate  at  which  the  impulses  descend  the  nerve  to 
arouse  a  voluntary  contraction.  One  difficulty  in  this  conclusion  is 
that  when  human  muscle  is  excited  by  eight  to  twelve  stimuli  per 
second,  we  obtain,  not  a  tetanic  contraction  with  a  few  irregularities 
superposed  on  it,  but  a  series  of  single  contractions,  the  so-called 
clonus.  In  order  to  produce  a  nearly  continuous  contraction  we 
must  employ  a  vibration  frequency  of  about  30  per  second.  It 
has  been  suggested  to  get  over  this  difficulty  that  under  normal 
circumstances  the  discharge  does  not  travel  along  all  the  nerve  fibres 
at  the  same  time,  so  that  the  different  muscle  fibres  composing  the 
muscle  will  be  in  different  phases  of  contraction,  and  there  will  be 
never  any  large  degree  of  relaxation  between  the  individual  con- 
tractions of  the  whole  muscle.  Von  Kries  has  found  that  the  duration 
of  a  muscle  twitch  may  be  lengthened  by  lengthening  the  duration 
of  the  electrical  change  used  to  excite  the  nerve,  and  has  suggested 
that  the  normal  excitatory  process  may  resemble  the  prolonged 
electrical  change  which  can  be  produced  electro-rnagnetically,  rather 
than  the  short  sudden  shock  represented  by  the  induced  current 
of    an    induction-coil.     Attempts   have   been   made   to   decide   the 


VOLUNTARY  CONTRACTION  269 

question  by  recording  the  electrical  changes  accompanying  the 
natural  contractions  of  a  muscle,  i.e.  those  excited  reflexly  from 
the  central  nervous  system.  It  was  long  ago  shown  by  Loven  that 
a  certain  discontinuity  could  be  seen  in  records  of  the  electrical  changes 
obtained  from  a  frog's  muscle  in  the  tetanic  spasms  produced  by 
an  injection  of  strychnine,  but  according  to  Burdon  Sanderson  this 
discontinuity  represents  a  series  of  spasms  discharged  from  the  central 
nervous  system.  Each  discharge  produces,  not  a  twitch,  but  a  con- 
tinued contraction  of  short  duration.  On  photographing  the  electrical 
changes  of  strychnine  spasm  as  obtained  by  a  capillary  electrometer, 
he  found  that  each  individual  spasm  could  only  be  compared  to  a 
short  tetanus.     The  most  recent  investigations  of  the  question  we 


Fig.  94.     Electrical  variations  produced  by  voluntarj-  contraction.s  of 
human  muscle.     (Piper). 

owe  to  Piper,  who  made  use  of  the  string  galvanometer,  an  instru- 
ment much  more  delicate  in  the  reproduction  of  rapid  changes  than 
is  the  capillary  electrometer.  Piper  led  off  two  points  in  the  fore-arm, 
one  electrode  being  placed  about  two  inches  below  the  bend  of  the 
elbow,  and  the  other  about  four  inches  above  the  wrist.  A  single 
stimulus  of  the  median  nerve  was  found  by  him  to  give  a  typical 
diphasic  variation  in  the  muscles.  When  the  muscles  were  con- 
tracted voluntarily,  well-marked  oscillations  of  the  galvanometer 
wire  were  obtained,  indicating  the  existence  in  the  muscle  of  fortv- 
eight  to  fifty  complete  diphasic  variations  in  the  second  (Fig.  94) .  Piper 
obtained  similar  records  on  leading  ofE  other  muscles  of  the  body 
when  these  were  placed  voluntarily  in  a  state  of  contraction,  and  he 
concludes  therefore  that  each  voluntary  contraction,  short  or  long, 
is  a  tetanus  composed  of  about  fifty  fused  twitches  per  second.  These 
results  would  indicate  that  the  impulse,  which  normally  travels  down 
the  motor  nerve  from  the  anterior  cornual  cell  to  the  muscle,  is 
discontinuous,  and  therefore  that  on  leading  ofE  a  motor  nerve  to 
a  galvanometer  we  ought  to  obtain  electrical  oscillations  of  fifty 
distinct  stimuli  per  second.  This  matter  has  been  taken  up  by 
Dittler,  who  has  investigated  by  means  of  the  string  galvanometer 
the  electrical  changes  accompanying  the  ordinary  contractions  of 
the  diaphragm,  and  also  those  occurring  in  the  phrenic  nerve.  He 
finds  thj^t  both  in  the  muscle  {ind  in  the  nerye  there  is  evidence  that 


270  PHYSIOLOGY 

each  contraction  is  a  fused  series  of  single  contractions,  evoked  by 
the  discharge  along  the  nerve  of  between  fifty  and  seventy  excita- 
tions per  second.  So  far  therefore  the  evidence  is  in  favour  of  the 
view  that  voluntary  contraction,  and,  one  must  add,  the  tonic  con- 
tractions of  all  skeletal  muscles,  are  discontinuous  in  nature  and 
analogous  to  the  tetanus  which  we  may  evoke  artificially  by  rapid 
stimulation  either  of  muscle  or  of  its  motor  nerve. 


SECTION  X 
OTHER  FORMS  OF  CONTRACTILE  TISSUE 

SMOOTH   OR  UNSTRIATED   MUSCLE 

The  little  we  know  about  the  physiology  of  unstriated  muscle  is 
derived  chiefly  from  experiments  on  the  intestine,  ureter,  bladder^  and 
retractor  penis.*  This  tissue  differs  from  voluntary  muscle  in  con- 
taining numerous  plexuses  of  nerve  fibres  (non-medullated)  and 
ganglion-cells,  so  that  in  all  our  researches  it  is  difl&cult  to  be  certain 
whether  the  results  are  due  to  the  muscle  fibres  themselves,  or  to  the 
nerves  and  nerve- cells  which  are  so  intimately  connected  with  them  ; 
especially  as  we  have  as  yet  no  convenient  drug  like  curare,  by  aid 
of  which  we  might  discriminate  between  action  on  muscle  and  action 
on  nerve. 

The  differences  between  unstriated  and  voluntary  muscle,  although 
at  first  sight  very  pronounced,  on  further  investigation  prove  to  be 
in  most  cases  differences  of  degree  only,  qualities  and  reactions  which 
are  marked  in  involuntary  muscle  being  also  present  in  a  minor  degree 
in  the  more  highly  differentiated  tissue. 

The  contraction  of  smooth  muscle  is  so  sluggish  that  the  various 
stages   of   latent   period,   shortening,   and  relaxation    can   be   easily  j  / 
followed  with  the  eye.     The  latent  period  may  be  from  0-2  to  0-8    • 
second,  and  the  contraction  may  last  from  three  seconds  to  three 
minutes. 

Smooth  muscle  preserves  many  of  the  properties  of  undifferentiated 
protoplasm,  especially  an  automatic  power  of  contraction,  which  is 
regulated  by  the  condition  of  the  muscle.  Thus  whereas  the  voluntary 
muscle  is  intimately  dependent  on  its  connection  with  the  central 
nervous  system,  and  in  the  absence  of  this  is  reduced  to  a  flabby  inert 
tissue,  the  smooth  muscle,  isolated  from  all  its  nervous  connections, 

*  The  rolractor  penis,  which  i.s  found  in  the  dog,  cat.  horse,  liedgehog(lnit 
not  in  rabbit  or  man),  is  a  thin  band  of  longitudinallj'  arranged  unstriated 
muscle,  which  is  inserted  at  the  attachment  of  the  prepuce,  and  is  continued  back- 
wards in  a  sheath  of  connective  tis.sue  to  the  bulb,  where  it  divides  into  two 
slips,  which  pass  on  either  side  of  the  anus.  It  is  innervated  from  two  soiu-ccs, 
the  motor  fibres  being  derived  from  the  lumbar  sympathetic  and  runm'ng  to  the 
muscle  in  the  internal  pudic  nerve,  while  the  inhibitory  fibres  run  in  the  pehic 
visceral  nerves  (nervi  erigentes)  and  are  derived  from  the  second  and  third 
sacral  nerve -roots. 

271 


272  PHYSIOLOGY 

presents  in  many  cases  rhythmic  contractions,  and  can  carry  out  a 
peripheral  adaptation  to  its  environment.  These  rhythmic  contrac- 
tions are  almost  invariably  observed  if  the  muscular  tissue  be 
subjected  to  a  certain  amoimt  of  tension,  after  separation  from 
the  central  nervous  system.  The  rhythm  of  the  contractions  may 
vary  from  one  (spleen)  to  twelve  (small  intestine)  contractions  in  the 
minute. 

The  stimuli  for  smooth  muscle  are  essentially  the  same  as  for 
striated.  As  we  should  expect,  however,  from  the  sluggish  response 
of  this  kind  of  contractile  tissue,  the  optimum  rate  of  change  of 
current  which  excites  is  very  much  slower  than  in  the  case  of  striated 
muscle.  Thus  in  many  instances  a  single  induction  shock,  even  if 
very  strong,  is  powerless  to  excite  contraction,  and  the  make-induction 


Fig.  95.  At  the  cathode  k  there  is  a  small  line  of  constriction,  surrounded 
by  an  area  of  relaxation.  At  the  anode  itself  the  muscle  is  relaxed,  but 
is  strongly  contracted  on  each  side  of  the  anode,  so  that  on  rough  obser- 
vation it  would  be  thought  that  contraction  occurred  at  the  anode  itself. 

shock  of  long  dm'ation  and  low  intensity  is  always  more  efficacious 
than  the  short  sharp  break-induction  current.  A  still  better  stimulus 
is  the  make  or  break  of  a  constant  current.  When  the  latter  form  of 
stimulation  is  used,  response  occurs  at  the  make  sooner  than  at  the 
break,  and,  just  as  in  voluntary  muscle,  the  make  excitation  starts 
from  the  cathode  and  the  break  excitation  from  the  anode. 

All  apparent  exception  to  this  statement  is  afforded  by  the  behaviour  of 
certain  forms  of  involuntary  muscle.  In  the  intestine,  in  the  skin  of  worms, 
and  in  many  other  muscular  tubes  the  smooth  muscle-fibres  are  arranged  in 
two  definite  sheets,  one  consisting  of  longitudinal,  the  other  of  circular  fibres. 
If  non-polarisable  electrodes,  connected  with  a  constant  source  of  current,  be 
applied  to  the  surface  of  the  small  intestine,  when  the  current  is  made  there 
will  be  apparentlj'  a  strong  contraction  of  the  circular  coat  at  the  anode,  which 
spreads  up  and  do^vn  the  intestine,  and  a  linear  contraction  of  the  longitudinal 
coat  at  the  cathode.  The  same  result  is  observed  in  the  earthworm  and  leech. 
But  careful  observation  shows  in  each  case  that  the  irregularity  is  really  only 
apparent,  and  that  in  the  immediate  neighbourhood  of  the  anode  there  is 
relaxation  of  both  coats,  with  a  contraction  of  the  circular  coat  on  each  side, 
and  that  at  the  cathode  there  is  a  contraction  of  both  coats.  The  accom- 
panying diagram  (Fig.  95)  wiU  servo  to  show  the  condition  of  the  circular  coat 
at  each  electrode. 

As  a  matter  of  ftict,  in  poiisecjuence  pf  the  ftryangepi^nt  of  tlie  flbrps,  ^e  liave  j^ 


OTHER  FORMS  OF  CONTRACTILE  TISSUE  273 

the  neighbourhood  of  the  anode  a  number  of  places  (virtual  cathodes)  where 
the  current  is  leaving  the  muscle-cells  to  enter  inert  conducting  tissues,  and  in 
the  same  way  there  will  be  in  the  neighboxirhood  of  the  cathode  a  number  of 
virtual  anodes  (Fig.  96).  Thus  if  we  take  the  ureter  and  lead  a  current  through  it 
while  it  is  slung  up  in  thread  loops  serving  as  electrodes,  there  is  contraction  of 
both  coats  at  the  cathode  and  relaxation  of  both  at  the  anode.  If,  however,  the 
ureter  be  packed  in  a  pulp  of    blotting-paper  moistened  with  normal  sahne 


Fig.  96.  Diagram  to  show  the  spread  of  current  which  occurs  when  a 
current  is  led  through  a  tube  such  as  the  ureter  by  means  of  two  elec- 
trodes applied  to  its  surface.  It  wiU  be  noticed  that  while  +E  Ls  the 
anode,  there  are  immediately  bel  jwand  around  it  a  number  of  cathodes, 
E^,  E,„  E.,„  'E,,,,  due  to  the  current  leaving  the  muscle  to  flow  through 
indifferent  tissues.     (Biedekmaxn.) 

thus  allowing  the  current  to  leave  the  contractile  tissues  anywhere  along  the 
ureter,  we  get  the  .same  aberrant  results  of  stimulation  as  are  obtained  with  the 
intestine. 

SUMMATION.  If  two  stimuli  be  sent  into  a  voluntarv  muscle 
within  a  short  interval  of  time,  there  is  a  summation  of  effect,  the 
contraction  due  to  the  second  stimulus  being  piled,  so  to  speak,  on 
the  top  of  the  first  contraction.  That  a  maximal  twitch  is  not  as 
high  as  a  tetanus,  the  production  of  summation  of  many  twitches, 
is  due  to  the  fact  that  the  relaxation  processes  of  a  muscle  begin 
before  it  has  time  to  overcome  the  inertia  of  the  mass  moved,  and 
so  accomplish  its  maximum  shortening.  If  therefore  we  support 
the  muscle  in  any  way,  whether  by  screvnng  up  the  lever  (after-load- 
ing) or  by  sending  in  a  previous  stimulus.,  the  contraction  due  to  a 
stimulus  will  be  more  pronounced,  until  the  shortening  of  the  muscle 
attains  that  observed  in  tetanus.  For  the  same  reason  the  height  of 
a  single  twtch  in  relation  to  a  tetanus  of  the  same  muscle  increases  as 
we  slotv  the  contraction,  until,  with  a  prolongation  such  as  is  produced 
by  veratrin,  there  is  no  difference  at  all  between  the  height  of  a 
maximal  single  contraction  and  the  height  of  a  tetanus. 

These  considerations  would  lead  us  to  expect  no  trace  of  any 
process  analogous  to  summation  of  contraction  in  the  slowly  moving 
smooth  muscle.  In  the  heart  muscle  this  is  the  case,  no  increase  in 
the  height  of  a  contraction  being  produced  by  sending  in  one,  two, 
or  more  shocks  in  quick  succession.  When,  however,  we  record  the 
contractions  of  a  muscle,  such  as  the  retractor  penis,  which  is  more 
closely  under  the  control  of  the  nervous  system,  and  excite  with  a 
series  of  induction  shocks,   we  get  results  which  at  first  sight  are 

18 


274  PHYSIOLOGY 

exactlv  analogous  to  the  summation  of  contraction  in  a  voluntar}' 
muscle.  It  may  be  noticed,  however,  that  the  first  three  or  four 
stimuli  are  ineffective,  and  that  there  is  in  this  case  a  summation 
before  any  contraction  has  occurred,  a  summation  of  stimuli.  Each 
stimulus,  in  fact,  alters  the  state  of  the  contractile  tissue  and  makes  it 
more  ready  to  respond  to  the  next  stimulus,  so  that  the  stimuli  become 
more  and  more  effective.  If  time  is  allowed  for  the  muscle  to  relax 
between  successive  stimuli,  this  summation  is  evidenced  by  a  con- 
tinually increasing  height  of  contraction,  the  so-called  '  staircase.' 
It  mil  be  remembered  that  the  same  initial  increase  of  effect  was 
observed  when  voluntary  muscle  was  excited  by  continually  recurring 
stimuH  {v.  Fig.  69,  p.  234). 

We  shall  meet  with  other  examples  of  this  summation  of  stimuli 
when  dealing  with  the  physiology  of  the  central  nervous  system.  It 
is  indeed  a  fundamental  phenomenon  in  the  physiology  of  excitation, 

CHEMICAL  STIMULATION.  Strong  salt  solution  excites  con- 
tractions just  as  in  the  case  of  skeletal  muscle.  Many  drugs,  such  as 
physostigmin,  ergot,  salts  of  lead  and  barium,  digitalis,  may  act 
directly  on  smooth  muscle  and  cause  contraction.  As  one  would 
expect,  however,  from  the  greater  independence  of  the  smooth  muscle, 
the  action  of  these  drugs  varies  from  organ  to  organ,  muscle-fibres, 
which  apparently  are  histologically  identical,  reacting  diversely 
according  to  their  origin. 

MECHANICAL  STIMULATION.  Smooth  muscle  may  react  to  a 
local  pinch  or  blow  with  a  local  or  a  general  (propagated)  contraction. 
The  most  important  form  of  mechanical  stimulation  is  that  produced 
by  tension.  The  effect  of  increasing  the  tension  on  smooth  muscle 
may  be  twofold  :  causing  in  the  first  place  relaxation  and  in  the 
second  excitation  with  increased  contraction.  These  two  effects 
may  be  illustrated  by  taking  the  case  of  the  bladder.  If  this  viscus 
(which  is  surrounded  by  a  complete  coat  of  smooth  muscle)  has  all  its 
connections  ^vith  the  central  nervous  system  severed,  it  is  when  empty 
in  a  state  of  tonic  contraction.  If  fluid  be  injected  into  it  rapidly 
there  is  a  great  rise  of  pressure  in  its  cavity,  due  to  the  forcible  disten- 
sion. If;  however,  the  fluid  be  injected  slowly  the  bladder  muscle 
relaxes  to  make  room  for  it,  so  that  a  considerable  amount  of  fluid  may 
be  accommodated  in  the  bladder  without  any  great  rise  of  pressure. 
This  process  of  relaxation  has  its  limit.  If  the  injection  of  fluid  be 
continued  the  walls  begin  to  be  stretched  passively,  and  this  increased 
tension  acts  as  a  stimulus  causing  marked  rhythmic  contractions  of 
the  whole  bladder. 

In  the  same  way  the  response  of  a  smooth  muscle  to  an  electrical 
stimulus  is  much  increased  by  previous  increase  of  the  tension  on  the 
muscle  fibres. 


OTHER  FORMS  OF  CONTRACTILE  TISSUE  275 

PROPAGATION  OF  THE  EXCITATORY  STATE,  OR  WAVE  OF 
CONTRACTION.  On  stimulating  any  part  of  a  voluntary  muscle 
fibre,  a  wave  of  contraction  is  started  wliich  travels  to  each  end  of  the 
fibre,  but  no  further.  There  is  no  propagation  from  muscle  fibre  to 
muscle  fibre,  the  synchronous  contraction  of  the  whole  muscle  being 
brought  about  by  simultaneous  excitation  of  all  its  fibres.  It  is  doubt- 
ful whether  this  isolation  of  the  excitatory  state  is  found  in  smooth 
muscle.  As  a  rule  a  stimulus  applied  to  any  part  of  a  sheet  of  smooth 
fibres  may  travel  all  over  the  sheet  just  as  if  it  were  a  single  fibre.  It 
seems  probable  indeed  that  there  is  protoplasmic  continuity  by  means 
of  fine  bridge-hke  processes  between  adjacent  muscle-cells. 
And  even  in  the  absence  of  such  bridges  the  propagation  of 
the  contraction  could  be  easily  accounted  for.  Although  in 
the  case  of  voluntary  muscle  the  rule  is  isolated  contraction, 
yet  a  very  small  change  in  the  muscle,  such  as  that  produced 
by  partial  drying  or  by  pressure,  is  sufl&cient  to  cause  the 
contraction  to  spread  from  one  fibre  to  another.  Indeed  by  ^^^'  ^~- 
clamping  two  curarised  sartorius  muscles  together,  as  in  the 
diagram  (Fig.  97),  it  is  found  that  stimulation  of  the  muscle  a  causes 
contraction  of  the  muscle  b.  The  current  of  action  of  a  in  this  case 
has  served  to  excite  a  contraction  in  b. 

It  must  be  remembered  that  in  all  unstriated  muscle  the  fibres  are  sur- 
rounded by  a  network  of  non-mcdullated  nerve  fibres.  Some  physiologists 
are  inclined  to  ascribe  to  these  fibres  an  important  part  in  the  propagation 
of  the  contraction  wave.  In  the  case  of  the  heart  muscle,  however,  it  can 
be  shown  almost  conclusively  that  the  propagation  takes  place  independently 
of  nerve  fibres,  and  probably  the  same  is  true  for  many  kinds  of  involuntary 
muscle. 

INFLUENCE  OF  TEMPERATURE.  Smooth  muscle  is  extremely 
susceptible  to  changes  of  temperature  ;  as  a  rule  warming  causes 
relaxation,  while  application  of  cold  causes  a  tonic  contraction.  The 
condition  of  the  muscle  at  any  given  time  does  not  depend  only  on 
its  actual  temjDcratuie,  but  also  on  the  rapidity  with  which  this 
temperature  has  been  reached.  Thus  a  rapid  cooling  of  the  retractor 
penis  muscle  of  a  dog  from  35°  to  25°  may  cause  a  contraction  as 
extensive  as  would  be  produced  by  a  slow  cooling  to  5°  C.  On  warm- 
ing a  muscle  from  30°  to  50°  C.  it  lengthens  gradually  up  to  about 
40°,  and  it  may  then  undergo  a  marked  heat  contraction  (varying 
in  degree  in  different  muscles)  at  about  50°  C,  which  may  pass  off  at'a 
somewhat  higher  temperature.  It  is  killed  somewhere  between 
40°  and  50°  C.  It  seems  very  doubtful  wlietlier  any  true  rigor  mortis 
occurs  in  smooth  muscle.  The  hard  contracted  appearance  of  the 
smooth  muscle  in  a  recently  dead  animal  is  chiefly  conditioned  by  the 
fall  of  temperature.     On  excising  the  muscle  and  warming  it  up  to 


276 


PHYSIOLOGY 


body  temperature  it  may  again  relax  and  show  signs  of  irritability 
two  or  three  days  after  the  death  of  the  animal.  Different  smooth 
muscles,  however,  vary  very  much  in  their  tenacity  of  life. 

DOUBLE  INNERVATION.  Voluntary  muscle  is  absolutely  depen- 
dent for  its  activity  on  the  central  nervous  system.  Cut  off  from 
this  it  is  flabby  and  motionless.  Its  sole  function  is  to  contract 
efficiently  and  smartly  on  receipt  of  impulses  arriving  along  its  nerve. 
It  is  only  necessary  therefore  that  these  impulses  should  be  of  one 
character — motor,  and  we  know  that  each  fibre  of  a  muscle,  such  as 


Fig.  98.  Tracing  from  the  retractor  penis  muscle  of  the  dog,  showing 
lengthening  (inhibition)  on  stimulation  of  the  nervus  erigens,  and  a 
smart  contraction  on  stimulating  the  pudic  (motor)  nerve.  (Move- 
ments of  muscle  reduced  |.) 


the   sartorius,   receives   one   efferent  nerve   fibre  terminating  in  an 
end-plate. 

In  the  case  of  smooth  muscle  we  have  a  tissue  which  has  an 
activity  and  reactive  power  of  its  own,  and  apart  from  its  innerva- 
tion may  be  at  one  time  in  a  state  of  relaxation,  at  another  in  a  state 
of  tonic  contraction.  In  order  that  the  central  nervous  system 
should  have  efficient  control  over  such  a  tissue,  it  must  be  able  to 
influence  it  in  two  directions  :  it  must  be  able  to  induce  a  contraction 
or  increase  a  contraction  already  present,  and  it  must  also  be  able  to 
put  an  end  to  a  spontaneous  contraction,  i.e.  to  induce  relaxation.  In 
order  to  carry  out  these  two  effects,  smooth  muscle  receives  nerve 
fibres  of  two  kinds  from  the  central  nervous  system,  one  kind  motor, 
analogous  to  the  motor  nerves  of  skeletal  muscle,  the  other  kind 
inhibitory,  causing  relaxation  or  cessation  of  a  previous  contraction. 
All  these  fibres  belong  to  the  visceral  or  'autonomic  '  system.  They  are 
connected  with  ganglion-cells  in  their  course  outside  the  central  nervous 
system,  and  their  ultimate  ramifications  in  the  muscle  are  always  non- 
medullated.  A  typical  tracing  of  the  opposite  effects  of  these  two  sets 
of  nerves  is  given  in  Fig.  98. 


Fig.  99.  Tmcing  of  contraction 
of  adductor  muscle  of  claw 
of  crayfish,  showing  inhibi- 
tion resulting  from  stimula- 
tion of  its  nerve  (at  b)  by- 
means  of  a  constant  current. 
The  break  of  the  current 
causes  a  second  smaller  in- 
hibition.     (BlEDKBMANN.) 


OTHER  FORMS  OF  CONTRACTILE  TISSUE  277 

In  the  invertebrata  many  '  voluntary  '  striated   muscles  probably  possess 
a  double  innervation.      Thus  in  the  crayfish  the  adductor  muscle  of  the  claw 
consists  of  striated  muscular  fibres,  every  fibre  of  which  is  supplied  with  two 
kinds  of  nerve  fibres.     By  exciting  these  fibres 
one  may  get,  according  to  the  conditions  of  the 
experiment,    either    contraction    of    a    relaxed 
muscle  or  relaxation   of  a  tonically  contracted 
muscle  (Fig.  99). 

AMOEBOID  MOVEMENT 
AmcBboid  movement  is  seen  in  the 
unicellular  organisms  such  as  the  amoeba 
and  in  the  white  blood  corpuscles.  It  can 
occur  only  within  certain  limits  of  tem- 
perature (about  0°  C.  to  40°) ;  within  these 
limits  it  is  the  more  active  the  higher 
the  temperature.  At  about  45°  the  cell 
goes  into  a  condition  resembling  heat 
rigor. 

The  fluid  in  which  the  corpuscles  are  suspended  is  of  great 
importance.  Distilled  water,  almost  all  salts,  acids  and  alkalies,  if 
strong  enough,  stop  the  action  and  kill  the  cell. 

The  movements  are  also  stopped  by  COg  or  by  absence  of  oxygen. 

Artificial  excitation,  whether  electrical, 
chemical,  or  thermal,  causes  universal  con- 
traction of  the  corpuscle,  which  therefore 
assumes  the  spherical  form. 

CILIARY  MOVEMENT 
Cilia  are  met  with  in  man  in  nearly  the 
whole  of  the  respiratory  passages  and  the 
cavities  opening  into  them  in  the  genera- 
tive organs,  in  the  uterus  and  Fallopian 
tubes  of  the  female,  and  the  epididymis  of 
the  male,  and  on  the  ependyma  of  the 
central  canal  of  the  spinal  cord  and  its 
continuation  into  the  cerebral  ventricles. 

The  cilia  (Fig.  100)  are  delicate  taper- 
ing filaments  which  project  from  the  hyaline 
border  of   the  epithelial  cells.     There  are 
about  twenty  or  thirty  to  each  cell.     The 
hyaline   border  is  really  made  up  of  the  enlarged  basal  portions  of 
the  cilia. 

In  action  the  cilia  bend  suddenly  down  into  a  hook  or  sickle  form, 
and  then  return  more  slowly  to  the  erect  position.     This  movement  is 


JO-' 

Fig.  100.  Ciliated  ctiluinnar 
epithelium  from  the  trachea 
of  a  rabbit;  m^,  m^,  m^, 
mucus-secreting     cells. 

(SCHAFEK.)  , 


278  PHYSIOLOGY 

repeated  many  (twelve  to  twenty)  times  a  second,  and  thus  serves  to 
move  forward  mucus,  dust,  or  an  ovum,  as  the  case  may  be.  The 
movement  seems  to  be  entirely  automatic,  and  it  is  quite  unaffected 
by  nerves,  at  any  rate  in  all  the  higher  animals. 

There  is,  however,  a  functional  connection  between  all  the  cells  of 
a  ciliated  epithehal  surface,  so  that  movement  of  the  ciha,  started  in  one 
cell,  spreads  forward  as  a  wave,  just  as,  when  the  wind  blows,  waves  of 
bending  pass  over  a  field  of  corn. 

The  conditions  of  ciliary  action  are  the  same  as  those  for  amcBboid 
movement  of  naked  cells. 

The  minuteness  of  the  object  has  up  to  now  prevented  us  from 
deciding  whether  the  cilium  is  itself  actively  contractile,  or  whether  it  is 
simply  passively  moved  by  the  action  of  the  basal  part  situated  in  the 
hyahne  border  of  the  cell. 


CHAPTER  VI 
NERVE    FIBRES     (CONDUCTING  TISSUES) 


SECTION  I 

THE  STRUCTURE  OF  NERVE   FIBRES 

Oisr  stimulatiiiu-  the    nerve    of    a    nerve-muscle    preparation    at    anv 
part  by  electrical,   thermal,   or  mechanical    meanS;   the  stimulus  is 

followed,  after  a  very  short  interval,  by 
a  contraction  of  the  muscle.    This  obser- 
vation illustrates  the  two  functions  of 
nerve  fibres,  irritability  and  conducti- 
vity— that  is  to  say,  a  suitable  stimulus 
can  set  up  changes  in  any  part  of  the 
nerve,  which  are  transmitted  down  the 
nerve  without  any  visible  efiects  occur- 
ring in  it,  and  it  is  not  until  this  nervous 
change  has  reached  the  muscle  that  a 
visible  eSect  takes  place  in  the  shape  of 
a  contraction.     In  the  animal  body  a 
direct  excitation  of  the  nerve  fibre  in 
its  course  never  takes  place  under  nor- 
mal circumstances.     The  only  fmiction 
the  nerve  fibre  has  to  perform  is  that 
of  conducting  impulses  from  the  sense 
organs  at  the  periphery  to  the  central 
nervous  system,  and  efferent  impulses 
from  this  to  the  muscles  and  other  of 
its  servants.     Hence   it  is  absolutely 
essential    that    there    should    be    vital 
continuity  along  the  whole  length  ot 
the  fibre.     Damage  to  any  part:,  such 
as  by  crushing,  heat,  or  any  other  in- 
jurious  condition,  infallibly   causes    a 
block  to  the  passage  of  an  impulse. 

A  nerve  fibre  is  essentially  a  long 
process  or  arm  of  a  nerve-cell  (Fig.  101). 
The  cell  may  either  be  situated  on  the 
surface  of  the  body  or,  as  in  most  cases 
in  the  higher  animals,  may  be  withdrawn, 
279 


Fig.  101.  Diagram  of  a  motor  nerve- 
cell  with  its  nerve  fibre.  (After 
Barkek.) 

a.A, axon  hillock;  <Z,  dcndiites; 
tt.x,  axis  cylinder;  vi,  medullary 
sheath  ;    n.ll,  node  of  Ranviir. 


280 


PHYSIOLOGY 


from  the  surface  into  a  special  collection  of  cells  such  as  the  posterior  root 
ganglion,  or  may  be  one  of  the  mass  of  cells  and  interlacing  processes 
making  up  a  central  nervous  system.  All  nerves  are  alike  in  possessing 
as  their  conducting  part  the  continuous  strand  of  protoplasm  produced 
from  the  nerve-cell  and  known  as  the  axon  or  axis  cylinder.  By  special 
methods  the  axon  may  be  shown  to  be  made  up  of  fibrillse  or  neuro- 
fibrils, embedded  in  a  more  fluid  material  (Fig.  102).     These  neuro.- 


FiG.  102,     MeduUated  nerve  fibres,  showing  continuity  of  the  ncuro-fibrils 
across  the  node  of  Ranvier.     (Bethe.) 
a,  longitudinal ;  b,  transverse  section. 


fibrils  are  supposed  to  be  continuous  throughout  the  cell  and  the  axis 
cylinder  and  to  represent  the  essential  conducting  constituents  of  the 
nerve.  In  the  course  of  growth  the  nerves  develop  certain  histo- 
logical differences,  which  appear  to  bear  some  relation  to  the  nature  of 
the  processes  they  conduct  or  to  the  character  of  their  parent  cell. 
Thus  all  the  fibres  which  are  given  off  from  and  which  enter  the  central 
nervous  system,  i.e.  the  brain  and  spinal  cord,  belong  to  the  class  known 
as  medullated.  In  this  type  the  conducting  core  or  axis  cylinder  is 
surrounded  with  a  layer  of  apparently  insulating  material  known  as 
myelin,  forming  the  medullary  sheath,  or  the  sheath  of  Schwann. 
This  sheath  consists  of  a  fatty  material  composed  largely  of  lecithin. 


THE  STRUCTURE  OF  NERVE  FIBRES 


281 


and  staining  black  with  osmic  acid,  supported  in  the  interstices 
of  a  network  formed  of  a  horny  ubstance  known  as  neurokeratin. 
The  medullary' sheath  is  siurounded  by  a  structureless  membrane, 
the  primitive  sheath  or  neurilemma.  At  regular  intervals  a  break 
occurs  in  the  medullary  sheath,  the  neurilennna  coming  in  close 
contact  with  the  axis  cylinder.  This  break  is  the  node  of  Ranvier,  the 
intervening  portions  of  medullated  nerve  being  the  internodes.  In 
each  internode,  lying  closely  under  the  neiu:ilemma,  is  an  oval  nucleus 
embedded  in  a  little  granular  protoplasm.  The  medullated  nerve 
fibres  vary  considerably  in  diameter,  the  largest  fibres  being  dis- 
tributed to  the  muscles  and  skin,  the  smallest  carrying  impulses  from 
the  central  nervous  system  to  the  viscera.  The  latter  all  come  to 
an  end  in  some  collection  of  gangUon-cells  of  the  sympathetic  cham 


Non-meduUated  nerve  fibres.     (Schafeb.) 


or  peripheral  gangUa,  the  impulses  being  carried  on  to  their  destina- 
tion by  a  fresh  relay  of  non- medullated  nerve  fibres. 

The  non-medullated  fibres  (Fig.  103)  difier  from  the  medullated 
simply  in  the  absence  of  a  medullary  sheath.  They  possess,  in  many 
cases  at  any  rate,  a  primitive  sheath,  under  which  we  find  nuclei  lying 
closely  on  the  side  of  the  fibre  and  bulging  out  the  sheath.  In  their 
ultimate  ramifications  they  tend  to  form  close  networks  or  plexuses 
and  appear  to  lose  the  last  traces  of  a  sheath. 

The  medullated  nerves  are  bound  together  by  connective  tissue 
(endoneurium)  into  small  bmidles,  which  are  again  united  by  tougher 
connective  tissue  into  larger  nerve-trunks.  These  fibres  as  a  rule  branch 
only  when  in  close  proximity  to  their  destination,  and  then  the  branch- 
ing always  occurs  at  a  node  of  Ranvier. 

As  to  the  functions  of  the  myelin  sheath  in  the  medullated  nerve 
fibre  very  httle  is  kno^vn.  It  does  not  make  its  appearance  until  the 
axis  cylinder  is  formed,  and  is  apparently  derived  from  a  series  of  cells 
which  grow  out  from  the  spongioblasts  of  the  central  nervous  system 
and  form  a  chain  surrounding  the  out-growing  axons.  In  the  re- 
generation of  a  nerve  fibre  after  section  the  myehn  sheath  appears 
later  than  the  axon  in  the  peripheral  part  of  the  nerve.  It  has  been 
supposed  by  some  to  act  as  a  sort  of  insulator  ensuring  isolated  con- 
duction within  any  given  nerve  fibre.  We  have,  however,  no  proof 
that  equally  isolated  conduction  is  not  possible  in  the  non-medullated 
fibres  of  the  visceral  system,  although  it  is  certainly  true  that  a  finer 
ordering  of  movements  is  required  in  the  skeletal  nuisck^s  than  in  the 
case  of   the  visceral   unstriated   muscles.      Moreover   ii\   the   central 


282  PHYSIOLOGY 

nervous  system  the  main  tracts  cannot  be  shown  to  be  functional 
before  the  date  at  which  they  acquire  their  medullary  sheaths,  sug- 
gesting that  previously  any  impulse  making  its  way  along  the  tract 
underwent  dissipation  before  arriving  at  its  destination.  It  is  possible 
too  that  the  myelin  sheath  may  serve  as  a  source  of  nutrition  to  the 
enclosed  axis  cyhnder,  which,  in  the  greater  part  of  its  course,  is  far 
removed  from  its  trophic  centre,  namely,  the  cell  of  which  it  is  an  out- 
growth. This  trophic  function  of  the  myehn  sheath  has  a  certain  basis 
of  fact  in  that  the  myelin  sheath  is  as  a  rule  larger  in  those  fibres  which 
take  the  longer  course. 


SECTION  II 

PROPAGATION  ALONG  NERVE  FIBRES 

The  velocity  of  propagation  along  a  nerve  fibre  may  be  measured, 
although  in  early  times  it  was  thought  to  be  as  instantaneous  as  the 
lightning  flash.  To  measure  the  velocity  of  propagation  in  a  motor 
nerve,  a  frog's  gastrocnemius  is  prepared,  with  a  long  piece  of  sciatic 
nerve  attached.  The  muscle  is  arranged  (Fig.  104)  so  that  its  con- 
traction may  be  recorded  on  a  rapidly  moving  surface,  on  which  are 


Fig.  104.  Diagram  of  arrangement  of  experiment  for  the  determination  of 
the  velocity  of  transmission  of  a  motor  impulse  down  a  nerve. 
The  battery  current  passes  through  the  primary  coil  of  the  inductorium 
c,  and  a  '  kick  over  '  key  k.  By  means  of  the  switch  s,  the  break  shock 
in  the  secondary  circuit  can  be  sent  through  the  nerve  n,  either  at  h  or 
at  a.  The  muscle  m  is  arranged  to  wTite  on  the  blackened  surface  of  a 
trigger  or  pendulum  myograph,  and  is  excited  during  the  passage  of  the 
recording  surface  by  the  automatic  opening  of  the  key  k.  (The  time- 
marker  is  not  showTi.) 


also  recorded,  by  means  of  electro- magnetic  signals,  the  moment  at 
which  the  stimulus  is  sent  into  the  nerve,  and  also  a  time-markinji 
showing  -05,7  sec.  Tracings  are  now  taken  of  the  contraction  of  the 
muscle  :  first,  when  the  nerve  is  stimulated  at  its  extreme  upper 
end  ;  secondly,  as  close  as  possible  to  the  muscle.  It  will  be  found  that 
the  latent  period,  which  elapses  between  the  point  at  which  the  stimu- 
lus is  sent  into  the  nerve  and  the  point  at  which  the  lever  begins  to  rise, 
is  rather  longer  in  the  first  case  than  in  the  second.  The  difference 
in  the  two  latent  periods  gives  the  time  that  the  nervous  impulse  has 
taken  to  travel  down  the  length  of  nerve  between  the  two  stimulated 
points.  Calculated  in  this  way  the  velocity  of  propagation  in  frog's 
nerve  is  about  28  metres  per  second. 

In  man  and  in  warm-blooded  animals  the  velocity  has  been  variously 

283 


284 


PHYSIOLOGY 


The  higher  of  these 


estimated  at  from  60  to  120  metres  per  second, 
figures  is  probably  nearer  the  truth. 

On  the  other  hand,  in  invertebrata  the  velocity  of  propagation  along  nerve 
fibres  may  be  quite  slow.  The  following  Table  represents  the  velocity  of  trans- 
mission along  a  number  of  different  fibres,  as  determined  by  Carlson,  compared 
\vitli  the  duration  of  single  muscle-twitch  in  the  same  animal. 


Species 

Muscle 

Nerve 

Contrac- 

Bate of 

Muscle 

tion 
time  in 
seconds 

Xerve 

the  impulse 
in  metres 
per  second 

Frog 

Gastrocnemius   . 

0-10 

Sciatic 

(medullated) 

27-00 

Snake 

Hyoglossus 

0-15 

Hyoglossal 
(medullated) 

14-004 

Lobster 

Adductor  of 

0-25 

Ambulacral 

12-00 

(Homarus) 

forceps 

(non-medullated) 

Hagfish     . 

Retractor  of  jaw 

0-18 

Mandibular 

(non-medullated) 

4-50 

Limulus    . 

Adductor  of 
forceps 

1-00 

Ambulacral 

(non-medullated) 

3-25 

Octopus    . 

Mantle 

0-50 

Pallial 

(non-medullated) 

2-00 

Slug  (Limax)     . 

Foot 

4-00 

Pedal 

( non-medullated ) 

1-25 

Limulus     . 

Heart 

2-25 

Nerve  plexus  in  heart 
(non-medullated) 

0-40 

V 


The  velocity  of  propagation  in  sensory  nerves  is  more  difficult 
to  determine  owing  to  the  fact  that  a  sensory  impulse,  on  arrival  at 
the  receiving  organ — i.e.  some  part  of  the  central  nervous  system — 
does  not  at  once  give  rise  to  some  definite  recordable  mechanical  change, 
such  as  a  muscular  contraction.  There  is  another  method  of  deter- 
mining the  velocity  of  conduction,  which  may  be  used  also  with 
sensory  fibres.  The  passage  of  a  nerve-impulse  down  a  nerve,  just 
as  the  passage  of  a  wave  of  contraction  along  a  muscle  fibre,  is  imme- 
diately preceded  or  accompanied  by  an  electrical  change,  which  also 
travek  along  the  nerve  as  a  wave  of  '  negativity.'  The  velocity  of 
propagation  of  this  wave  may  be  measured,  and  is  found  to  give 
the  same  numbers  as  the  velocity  determined  by  the  preceding 
method. 

The  existence  of  this  electrical  change  enables  us  to  show  that  a 
nerve- impulse,  excited  at  any  point  in  the  course  of  a  nerve  fibre, 
travels  in  both  directions  along  the  fibre.     The  power  of  nerves  to 


PROPAGATION  ALONG  NERVE  FIBRES  285 

transmit  impulses  in  either  direction  is  shown  further  by  the  experi- 
ment known  as  Kiihne's  gracilis  experiment.  The  gracilis  muscle  of  the 
frog  is  separated  into  two  portions  by  a  tendinous  intersection,  so 
that  there  is  no  muscular  continuity  between  the  two  halves.  The 
nerve  to  the  muscle  divides  into  two  branches,  one  to  each  half,  and  at 
the  point  of  junction  there  is  division  of  the  axis  cylinders  therm 
If  the  section  a  iiTtEe  diagram  (Fig.  105),  which  is  quite  isolated 
from  the  rest  of  the  muscle,,  be  stimulated,  as  by  snipping  it  with 
scissors,  the  whole  muscle  contracts.  If  the  portion  of  the  muscle 
which  is  free  from  nerve  fibres  be  stimulated  in  the 
same  way,  the  contraction  is  limited  to  the  fibres 
directly  stimulated,  showing  that  in  the  first  case  the 
stimulus  excited  nerve  fibres  which  transmitted  the 
impulse  up  the  nerve  to  the  point  of  division  and 
then  down  again  to  the  other  half  of  the  muscle. 

Since  nerves  have  this  power  of  conduction  in  both 
directions,  it  might  be  thought  that  a  single  set  of 
nerve  fibres  might  very  well  subserve  both  afferent 
and  efferent  functions,  at  one  time  conducting  sensory 
impulses  from  periphery  to  cord,  at  another  time 
motor  impulses  from  cord  to  muscles.  But  this  is  „..  ■^^°,- ^^^•.,. 
not  the  case.  As  a  matter  of  fact  we  find  in  the  experiment, 
body  a  marked  differentiation  of  function  between 
various  nerve  fibres.  Thus  Bell  and  Majendie  showed  that  the 
spinal  roots  might  be  divided  into  afferent  and  efferent,  the  anterior 
root  carrying  only  impulses  from  spinal  cord  to  periphery,  while  the 
posterior  roots  carried  impulses  from  periphery  to  central  nervous 
system.  The  law  known  by  the  name  of  these  observers  states  indeed 
that  a  nerve  fibre  cannot  be  both  motor  and  sensory.  We  may  find 
both  kinds  of  fibres  joined  together  into  a  single  nerve-trunk,  but 
the  fibres  in  each  case  are  isolated  and  conduct  impulses  only  in  one  or 
other  direction.  Under  normal  conditions  the  afferent  fibres  are 
excited  only  at  their  endings  on  the  surface  of  the  body,  while  the 
efferent  fibres  are  excited  only  at  their  origin  from  the  spinal  cord.  The 
difference  in  the  function  of  different  nerve  fibres  depends  therefore 
not  so  much  on  the  structure  of  the  nerve  fibre  itself  as  on  the  con- 
nections of  the  fibre.  We  can  show  this  experimentally  by  grafting 
one  set  of  nerve  fibres  on  to  another.  If  the  cervical  sympathetic  be 
united  to  the  lingual  nerve,  stimulation  of  the  sympathetic,  instead  of 
causing,  as  usual,  constriction  of  the  vessels  of  the  head  and  neck,  will 
jcause  dilatation  of  the  vessels  of  the  tongue  and  secretion  of  watery 
saliva.  In  the  same  way  the  finer  functional  differences  between  the 
various  forms  of  sensory    nerves  seem   to  be   determined  [by    their 


286  PHYSIOLOGY 

connections  within  the  central  nervous  system.  Stimulation  of  the  optic 
nerve  by  any  means  whatsoever  evokes  a  sensation  of  light.  One  and  the 
same  stimulus  applied  to  different  nerves  will  evoke  different  sensations, 
e.g.  a  tuning-fork  apphed  to  the  skin  will  give  a  sensation  of  vibration, 
to  the  ear  a  sensation  of  sound.  We  shall  have  occasion  to  return  to 
this  question  of  the  restricted  function  of  nerve  fibres  when  we  deal 
with  MUller's  '  law  of  specific  irritability '  in  the  chapter  on 
Sensations. 


SECTION  in 

EVENTS  ACCOMPANYING  THE  PASSAGE  OF  A 
NERVOUS  IMPULSE 

In  muscle  we  saw  that  the  passage  of  an  excitatory  wave  wad 
accompanied  or  followed  by  electrical  changes,  production  of  heat,  and 
mechanical  change,  all  pointing  to  an  evolution  of  energy  from  the 
explosive  breaking  down  of  contractile  material. 

In  nerve,  however,  which  serves  merely  as  a  conducting  medium,  we 
should  not  expect  so  much  expenditure  of  energy,  or  in  fact  any 
expenditure  at  all.  All  that  is  necessary  is  that  each  section  of  the 
nerve  should  transmit  to  the  next  section  just  so  much  kinetic  energy 
as  it  has  received  from  the  section  above  it.  And  experiment  bears 
out  this  conclusion.  The  most  refined  methods  have  failed  to  detect 
the  slightest  development  of  heat  in  a  nerve  during  the  passage  of 
an  excitatory  process,  and  we  know  already  that  there  is  no  mechani- 
cal change  in  the  nerve.  The  only  physical  change  in  a  nerve  under 
these  circumstances  is  the  development  of  a  current  of  action.  A  nerve 
becomes,  when  excited  at  any  point,  negative  at  this  point  to  all  other 
parts  of  the  nerve,  and,  just  as  in  muscle,  this  '  negativity  '  is  pro- 
pagated in  the  form  of  a  wave  in  both  directions  along  the  nerve. 

That  the  excitatory  process  in  nerves  is  probably  accompanied 
by  certain  small  chemical  changes  is  indicated  by  the  facts  that,,  in  the 
complete  absence  of  oxygen,  the  nerve  fibres  lose  their  irritability,  and 
that  this  loss  of  irritability  is  hastened  by  repeated  stimulation  of  the 
nerve.  When  the  irritability  has  been  abolished  by  stimulation  in 
the  absence  of  oxygen,  it  may"  be  restored  within  a  few  minutes  by 
readmission  of  oxygen  to  the  nerve. 

If  we  connect  a  galvanometer  to  two  points  of  an  uninjured  nerve, 
no  current  is  observed,  all  points  of  a  living  nerve  at  rest  being  iso- 
electric. On  making  a  cross-section  of  the  nerve  at  one  leading-off 
point,  a  current  is  at  once  set  up,  which  passes  from  the  surface  through 
the  galvanometer  to  the  cross-section.  This  is  a  demarcation  current, 
set  up  at  the  junction  between  living  and  dying  nerve.  This  current 
rapidly  diminishes  in  strength  and  finally  disappears,  owing  partly 
to  the  fact  that  the  dying  process  started  in  the  nerve  by  the  section 
extends  only  as  far  as  the  next  node  of  Ranvier  and  there  ceases, 
so  that  after  a  short  time  the  electrode  applied* to  the  cross-section  is 

287 


288  PHYSIOLOGY 

simply  leading  off  an  intact  living  axis  cylinder  through  the  dead 
portion  of  the  nerve,  which  acts  as  an  ordinary  moist  conductor.  On 
making  a  fresh  section  just  above  the  previous  one,  the  process  of 
dying  is  again  set  up,  and  the  demarcation  current  is  restored  to  its 
original  strength.  If,  while  the  demarcation  current  is  at  its  height, 
we  stimulate  the  other  end  of  the  nerve  with  an  interrupted  current, 
the  needle  of  the  galvanometer  swings  back  towards  zero,  i.e.  there 
is  a  negative  variation  of  the  resting  current. 

In  order  to  demonstrate  the  wave-like  progression  of  the  electrical 
change  from  the  excited  spot  along  the  nerve,  it  is  necessary,  as  in  the 
case  of  muscle,  to  make  use  of  a  very  sensitive  capillary  electrometer 
or  a  string  galvanometer.  It  is  then  found  that  the  change  progresses 
along  the  nerve  at  the  same  rate  as  the  nervous  impulse,  i.e.  28  to 
33  metres  per  second  in  the  frog.  But  it  lasts  only  an  extremely 
short  interval  of  time  at  each  spot,  viz.  six  to  eight  ten-thousandths 
of  a  second.  Thus  the  length  of  the  excitatory  wave  in  nerve  is  about 
18  mm. 


SECllOX  IV 


CONDITIONS   AFFECTING  THE  PASSAGE   OF   A 
NERVOUS  IMPULSE 

TEMPERATURE.  Below  a  certain  temperature  the  propagation 
of  the  excitatory  process  in  the  nerve  is  absolutely  abolished.  The 
exact  temperature  at  which  this  occurs  varies  according  as  we  use  a 
warm-  or  a  cold-blooded  animal.     In  the  ^ 

frog  it  is  necessary  to  cool  the  nerve  below 
0°  C.  before  conduction  is  abolished,  whereas 
in  the  mammal  it  is  sufficient  to  cool  the 
nerve  to  somewhere  between  0^  and  5°  C. 
Since  cooling  the  nerve  does  not  excite  it, 
this  procedure  forms  a  convenient  method 
for  blocking  the  passage  of  impulses  along 
a  nerve  without  using  the  irritating  pro- 
cedure of  section.  On  warming  the  nerve 
again  the  conductivity  returns.  The 
rapidity  with  which  the  excitatory  pro- 
cess is  propagated  along  either  a  nerve  or 
a  muscle  fibre  depends  on  the  tempera- 
ture. Thus  the  mean  rate  of  conduction 
in  the  frog's  nerve  at  8^  to  9°  C.  is  about 
16  metres  per  second.  The  temperature 
coefficient  of  the  velocity  of  nerve  propa- 

velocity  at  Tn  +  10  ,        , 

gation,  I.e.   --^—. ■ has   been 

velocity  at  Tn 

found  by  Lucas  to  be  about  T79.     The 

same   value   was   found    by   Maxwell   for 

conduction    in    molluscan   nerve,    and    in 

frog's  striated  muscle  Woolley  found  the 

temperature  coefficient  for  conduction  of  the  excitatory  process  to 

vary  between  1-8  and  2. 

An  ingenious  method  (Fig.  106)  has  boeu  used  by  Keith  Lucas  for  the  determina- 
tion of  the  conduction  rates  in  nerve  at  different  tenii>eratures.  The  glass  vessel 
represented  in  the  figiu-o  is  filled  with  Ringer's  solution,  in  which  the  whole 
nerve-musclo  preparation  is  immersed.  The  muscle  used  was  the  flexor  longus 
digitorum,  so  that  the  whole  length  of  the  sciatic,  tibial,  and  sural  nerves  could 
bo  used.     The  nerve  is  passed  up  throu<ih  the  constrictions  in  the  inner  glass 

2S9  lU 


290 


PHYSIOLOGY 


vessels  at  c  and  d.  and  is  attached  to  the  thread.  F,  i,  and  G  are  three  non- 
pohu-isabk'!  electrodes  conii)osed  of  porous  clay,  containing  saturated  zinc 
sulphate,  in  -which  a  zinc  rod  is  immersed.  If  the  current  is  passed  in  at  G 
and  out  at  F  the  effective  cathode  is  at  the  lower  end  of  the  constriction  c,  and 
similarly  if  the  current  is  passed  in  at  I  and  out  at  G,  the  effective  cathode  is 
at  D.  The  tendon  of  the  muscle  a  is  attached  by  a  thin  glass  rod  H  to  a  very 
light  recording  lever,  the  movement  of  which  is  magnified  by  placing  it  in  the 
focal  plane  of  a  projecting  eye-piece  and  recording  its  image  on  a  moving  sensi- 
tive plate.  The  whole  apparatus,  with  the  exception  of  the  glass  rod  at  H, 
can  be  immersed  in  a  water  bath  at  any  given  temperature.     Two  records  are 


Fig.  107.     Curve  of  muscle-twitch  obtamed  by  foregoing  method. 

(Keith  Lucas.) 

A  =  moment  of  excitation,    b  =  movement  of  muscle,    c  =  time-marker. 

taken  with  the  whole  apparatus,  first  stimulating  at  c,  and  secondly  stimu- 
lating at  D.  The  difference  between  the  latent  periods  in  these  two  cases  is 
the  time  taken  for  the  excitatory  wave  to  travel  from  D  to  c.  The  rate  of 
propagation  is  similarly  recorded  when  the  water  bath  is  raised  to  18°  C.  or  to 
s,ny  desired  temperature.  Since  we  are  only  dealing  with  differences  in  latent 
periods  the  effect  of  the  rise  of  temperature  on  the  latent  period  of  the  muscle 
itself  does  not  affect  the  determinations. 

THE  INFLUENCE  OF  FATIGUE.  In  the  description  of  the 
phenomena  of  muscnlar  fatigue  given  in  the  last  chapter  it  was  assumed 
that  the  muscle  was  being  excited  directly.  The  same  phenomena 
are  observed  when  the  muscle  is  excited  through  its  nerve,  though 
in  this  case  fatigue  comes  on  much  more  quickly.  If,  after  the  nmscle 
has  been  excited  in  this  way  vmtil  exhausted,  it  be  excited  directly,  it 
will  respond  with  a  contraction  nearly  as  high  as  at  the  beginning  of  the 
experiment.  We  see  therefore  that  the  nervous  structures  are  more 
susceptible  to  the  influences  causing  fatigue  than  the  nuiscle  itself,  and 
it  can  be  shown  that  the  weak  point  in  the  nerve- muscle  preparation  is 
not  the  nerve,  but  the  end-plates.  In  fact  it  is  not  possible  to  demon- 
dirate  any  phenomena  of  fatigue  in  the  nerve-trunk.*  This  fact  can 
*  Unless  it  be  asphyxiated  by  total  deprivation  of  oxygen. 


CONDITIONS  AFFECTING  A  NERVOUS  TMPIU.SE       201 

be  shown  in  ntatnnuila  by  poisoniniz  the  animal  with  curare,  and  then 
stiunilatint^  a  motor  nerve  continuously  while  tlie  animal  is  kept  alive 
by  means  of  artificial  respiration.  As  the  eftect  of  the  curare  on  the 
end-plates  begins  to  wear  off  in  consequence  of  its  excretion,  the  muscles 
supplied  by  the  stimulated  nerve  enter  into  tetanus.  The  action  of  the 
curare  may  be  cut  short  at  any  time  by  the  injection  of  salicylate 
of  physostigmin,  when  the  muscles  will  at  once  begin  to  react  to  the 
excitation. 

The  same  fact  may  be  shown  on  the  excised  nerve- muscle  prepara- 
tion of  the  frog.     The  sastrocnemii  of  the  two  sides  with  the  sciatic 


Fig.  108.     Arrangement  of  experiment  for  demonstrating  the  absence  of 

fatigue   in  meduUated   nerve-fibres. 

EC,  exciting  circuit ;    cp,  ijolarising  circuit. 


ner/es  are  dissected  out,  and  an  exciting  circuit  is  so  arranged  that  the 
interrupted  secondary  currents  pass  through  the  upper  ends  of  both 
nerves  in  series  (Fig.  108).  At  the  same  time  a  constant  cell  is  connected 
with  two  non-polarisable  electrodes  {np,  np)  placed  on  the  nerve  of  b, 
so  that  a  current  runs  in  the  nerve  in  an  ascending  direction.  The  effect 
of  passing  a  constant  current  through  a  nerve  is  to  block  the  passage 
of  impulses  through  the  part  traversed  by  the  current.  When  the 
constant  polarising  current  is  made,  the  muscle  B  may  give  a  single 
twitch,  and  then  remains  quiescent.  The  exciting  current  is  then  sent 
through  both  nerves  by  the  electrodes  e^  and  e^.  The  muscle  a  enters 
into  tetanus,  which  gradually  subsides  owing  to  "  fatigue."  When  a 
no  longer  responds  to  the  stimulation,  the  constant  current  through 
the  nerve  of  n  is  broken,  b  at  once  enters  into  tetanus,  which  last,s  as 
long  as  tlie  contraction  (1i;l  in  the  case  of  a.  and  L;r.KliiaIl\-  subsides  as 


292  PHYSIOLOGY 

fatigue  comes  on.  Since  both  nerves  have  been  excited  throughout,  it 
is  evident  that  the  fatigue  does  not  affect  the  ueive-trunk.  We  have 
aheady  seen  that  a  muscle  will  respond  well  to  direct  stimulation  when 
stimulation  of  its  nerve  is  without  effect,  and  must  therefore  conclude 
that  the  first  seat  of  fatigue  is  the  junction  of  nerve  and  muscle,  i.e.  the 
end- plates. 

In  the  normal  intact  animal  the  break  in  the  neuro-muscular 
chain  which  is  the  expression  of  fatigue  occurs  still  higher  up,  i.e.  in 
the  central  nervous  system,  and  is  probably  due  to  some  reflex  inhibi- 
tion of  the  central  motor  apparatus  from  the  muscle  itself.     Thus  after 


Fig.  109. 

complete  fatigue  has  been  produced  in  a  muscle  so  far  as  regards 
voluntary  eSorts,  direct  stimulation  of  the  muscle  itself  or  its  nerve 
will  produce  a  contraction  as  great  as  would  have  been  the  case  at  the 
beginning  of  the  experiment. 

THE  INFLUENCE  OF  DRUGS.  The  most  important  drugs  with  an 
influence  on  nerve  fibres  are  those  belonging  to  the  class  of  anaes- 
thetics. Of  these  we  may  mention  carbon  dioxide,  ether,  chloroform, 
and  alcohol. 

The  action  of  any  of  these  substances  on  the  excitability  and  conductivity 
of  a  nerve  may  be  studied  by  ineans  of  tlie  simple  apparatus  represented  in 
Fig.  109.  The  nerve  of  a  nerve-muscle  preparation  is  passed  through  a  glass  tube 
which  is  made  air-tight  by  plugs  of  normal  saline  clay  surrounding  the  nerve 
at  the  two  ends  of  the  tube.  By  means  of  two  lateral  tubulures  a  current  of 
CO2,  or  air  charged  with  vapour  of  ether  or  other  narcotic,  can  be  passed  through 
the  tube.  The  nerve  is  armed  with  two  pairs  of  electrodes  which  are  stimu- 
lated alternately,  the  pair  within  the  tube  serving  to  test  the  action  of  the  drug 
on  the  excitability,  while  the  pair  outside  the  tube  shows  the  presence  or  absence 
of  any  effect  on  the  conducting  power  of  the  nerve  below  it. 

Of  the  gases  and  vapours  mentioned  above,  CO2  and  ether  both 
diminish  and  finally  abolish  the  excitabihty  and  conductivity  of  the 
nerve  fibres.  Ihe  conductivity,  however,  persists  after  all  trace  of 
excitability  has  disappeared,  before  in  its  turn  being  also  abolished. 


CONDITIONS  AFFECTING  A  NERVOUS  IMPULSE      293 

On  removing  the  gas  or  vapour  by  blowing  air  over  the  nerve,  the 
conductivity  and  excitability  gradually  return  in  the  reverse  order  to 
their  disappearance  (Fig.  110) 


Fig.  110.  Tracixig  to  show  the  effect  of  ether  on  excitability  and  conductivit}'  of 
nerve.  Nerve  excited  by  single  induction  shocks  alternately  -nithin  and  above 
ether  chamber.  The  vertical  lines  indicate  contractions  of  tho  muscle  (gastroc- 
nemius). The  lower  line  indicates  the  periods  during  which  tho  nerve  was  exposed 
to  the  action  of  ether. 

A,  disappearance  of  excitahility ;  B,  reappearance  of  excitahility ;  c,  disap- 
pearance of  conductivity ;  x>,  reappearance  of  conductivity.  (From  a  tracing 
kindly  lent  by  Prof.  Gotch.) 

Alcohol  is  said  to  increase  the  excitability  or  leave  it  unaffected, 
while  diminishing  the  conductivity  of  the  nerve. 

Chloroform  rapidly  abohshes  both  excitability  and  conductivity. 
It  is  a  much  more  severe  poison  than  the  drugs  just  mentioned,  so 
that  in  many  cases  its  effects  are  permanent,  and  no,  or  only  a  very 
partial,  recovery  of  the  nerve  is  obtained  on  removal  of  the  ch'oro- 
form  vapour  from  the  apparatus. 


SECTION  V 

THE  EXCITATION  OF  NERVE   FIBRES 

Many  different  forms  of  stimuli  may  be  used  to  arouse  the  activity 
of  an  excitable  tissue  such  as  muscle  or  nerve.  Thus  we  may  use 
thermal,  mechanical,  or  chemical  stimuli.  If  the  temperature  of  a 
motor  nerve  be  gradually  raised,  no  effect  is  noticed  till  about  40°  C. 
is  reached,  when  the  muscle  may  enter  into  weak  quivering  contrac- 
tions. Sudden  warming  of  the  nerve  always  gives  rise  to  excitation. 
At  about  45°  C.  the  nerve  loses  its  irritability  and  dies.  On  the  other 
hand,  a  nerve  may  be  rapidly  cooled  without  any  excitation  taking 
place. 

A  nerve  may  be  excited  mechanically  by  crushing  or  cutting. 
These  methods  destroy  the  nerve.  It  is  possible  to  excite  a  nerve 
mechanically,  without  any  serious  injury  to  it,  by  carefully  gTaduated 
taps,  and  this  method  has  been  used  in  investigating  the  phenomena 
of  electrotonus. 

All  chemical  stimuli  applied  to  the  nerve  have  a  speedy  effect  in 
destroying  its  irritability.  The  chemical  stimuli  most  used  are  strong 
salt  solutions,  glycerin,  or  weak  acids.  If  any  one  of  these  be 
applied  to  a  motor  nerve,  the  muscle  enters  into  an  irregular 
tetanus,  which  lasts  till  the  irritability  of  the  nerve  is  destroyed  at 
the  part  stimulated. 

None  of  these  forms  of  stimuli  can  be  adequately  controlled  either 
as  to  strength  or  duration.  Moreover,  owing  to  their  destructive 
effects,  any  repetition  of  the  stimulus  will  fall  on  a  nerve  or  muscle 
more  or  less  altered  by  the  first  stimulus.  We  are  therefore  justified 
in  the  use  of  electrical  stimuli  not  only  for  arousing  the  activity  of 
excitable  tissues,  but  also  for  determining  the  conditions  of  excitation 
of  muscle  and  nerve.  For  this  purpose  we  may  use  either  the  make 
and  break  of  a  constant  ciu'rent,  the  induced  current  of  short  dura- 
tion produced  in  a  secondary  coil  of  an  inductorium  by  the  make  or 
break  of  the  primary  circuit,  or  the  discharge  of  a  condenser. 

The  last-named  method  of  stimulation  is  especially  useful  when  we  desire 
to  determine  the  total  amount  of  energy  involved  in  the  electrical  stimulation 
of  a  nerve  or  muscle.  The  arrangement  of  such  an  experiment  is  showii  in 
Fig.  111.  By  means  of  the  switch  S  the  condenses  can  be  put  into  connection 
either  with  the  battery  from  which  it  receives  its  charge  or  with  the  nerve 
through  which  it  can  discharge.     By  knowing  the  capacity  of  the  condenser 

294 


THE  EXCITATION  OF  NERVE  FIBRES 


205 


and  the  electromotive  force  by  which  it  is  charged,  we  can  estimate  the  energy 
of  the  charge  scut  tlirough  the  nerve. 

E  (energy  in  ergs)*  =  5FV2 
(F  =  capacity  in  microfarads  ;  V  =  electromotive  force  in  volts). 

In  this  way  it  has  been  found  that  the  energy  of  a  minimal  effective  stimulus 
for  frog's  nerv?  is  about  ,  ,/y  ,y  of  an  erg. 

The  amount  of  energy  necessary  to  excite  the  nerve  will  vary  with  the  rate 
at  which  the  condenser  is  allowed  to  discharge  through  the  nerve.  Its  rate 
can  be  modified  by  altering  the  resistance  in  the  discharging  circuit  or  by 
altering  the  electromotive  force  of  the  charge.  This 
method  has  been  adopted  by  Waller  in  determining 
the  rate  of  change  at  wiiich  excitation  is  obtained 
with  a  minimal  expenditure  of  energy,  which  he  caUs 
the  "characteristic"'  of  the  tissue  in  question.  To 
tliis  point  wc  shall  have  occasion  to  refer  later. 

When  using  the  make  and  break  of  a  con- 
stant current  as  a  stimulus,  the  first  fact  of 
importance  is  the  relation  of  the  seat  of  exci- 
tation to  the  poles  by  which  the  tiurrent  is 
led  into  or  out  of  the  excitable  tissue. 
We  have  already  seen  that  when  a 
current  is  passed  through  a  muscle 
or  nerve  the  muscle  contracts  only 
at  make  or  at  break  of  the  current, 
no  propagated  excitatory  effect  being 
produced  during  the  passage  of  the 
current.     The  excitation  at  make  is 
obtained  with  a  smaller  current  than 
the  excitation  at  break. 

Besides  this  difference  in  intensity,  there  is  a  difference  in  the 
point  from  which  excitation  starts.  A  make  contraction  starts  from 
the  cathode,  a  break  contraction  from  the  anode.  This  is  well  shown  by 
the  two  following  experiments  : 

(a)  A  curarised  sartorius  muscle  of  the  frog  (Fig.  112),  with  its 
bony  insertions  still  attached,  is  fastened  at  the  two  ends  to  two 
electrodes,  which  are  able  to  swing  when  the  muscle  contracts,  and  are 
attached  by  threads  to  levers  which  serve  Co  record  the  contraction. 
The  middle  of  the  muscle  is  then  fixed  by  clamping  it  lightly.  A 
circuit  is  arranged  so  that  a  constant  current  can  be  sent  through  the 
electrodes  and  the  whole  length  of  the  muscle.  It  is  found,  on  making 
the  current,  that  the  lever  attached  to  the  cathode — ^that  is,  to  the 

*  An  erg  is  the  amount  of  work  produced  or  energy  expended  by  the  action 
of  one  dyne  through  one  centimetie. 

A  djTio  is  the  force  which  will  give  to  a  mass  of  one  gram  an  acceleration  of 
one  centimetre  per  second  per  second. 


Fig.  111.     Arrangement  of  apparatus 
for  the  excitation  of  a   nerve   by 

means  of  condenser  discharges. 
B,  battery  ;  R,  rheochord  ;  c,  rider 
of  rheochord ;  s,  switch  (Pohl's 
reverser  without  cross  wires); 
c,  condenser;  n,  nerve;  m,  muscle; 
e,  non-polarisable  electrodes. 


296 


PHYSIOLOGY 


.-<^ 


electrode  by  which  the  current  leaves  the  muscle — rises  before  the 
other  lever.  On  the  other  hand,  on  breaking  the  current  the  lever 
at  the  anode  rises  first,  showing  that  the  anodic  half  of  the  muscle 
contracts  before  the  cathodic  half. 

(b)  The  irritability  of  a  muscle,  i.e.  its  power  of  responding  to  a 

stimulus  by  contracting,  is  inti- 
mately dependent  on  the  life  of 
the  muscle.  If  the  muscle  be 
injured  or  killed  at  any  spot,  its 

■^ ==»       ^  irritability  at  this  spot  will   be 

■^therefore   diminished  or   de- 
FiG.  112.   Sartorius  clamped  in  middle  and  ?troyed.     Hence,  if  we  stimulate 

attached  to  levers  at  either  end.  a  muscle  at  the  injured  spot,  no 

contraction  will  ensue.     This  fact 

may  be  used  to  demonstrate  the  production  of  excitation  at  cathode 

on  make,  and  at  anode  on  break  of  a  constant  current, 

A  muscle  with  parallel  fibres,  such  as  the  sartorius,  is  injured  at 

one  end,  and  a  constant  current  passed,  first  from  the  injured  to  the 

uninjured  end,  and  then  in  the  reverse  direction.     It  is  found  in  the 

former  case,  when  the  anode  is  on  the  injured  part  (which  is  therefore 

less  excitable),   that    break 

anode(injured) 

contraction  at  make. 


Uathode 


anode 


kathode  (injured) 
no  contraction  at  make. 


Fig,  113.  Diagram  to  show  the  effect  of  local 
injury  on  the  excitability  of  a  muscle. 
b,  battery ;  m,  muscle.  The  arrows  indicate 
the  direction  of  the  current. 


of  the  current  is  ineffective, 
and  in  the  latter,  when  the 
cathode  is  on  the  injured  sur- 
face, that  the  make  stimulus 
is  ineffective,  showing  that 
the  part  excited  corresponds 
to  the  cathode  at  make  and 
to  the  anode  at  break. 

"With  a  current  of  very 
short  duration  no  excitation 
is  produced  at  break.  Every 
induction  shock  can  be  therefore  regarded  as  a  make  stimulus,  and 
when  such  a  shock  is  led  through  a  muscle  the  contraction  in  each 
case  will  start  at  the  cathode,  i.e.  the  point  at  which  the  induction 
shock  leaves  the  muscle.'  The  results  of  stimulating  nerve-fibres  are 
similar  to  those  obtained  by  stimulating  muscle-fibres  directly. 

Under  normal  circumstances,  if  a  constant  current  be  passed 
through  the  nerve  of  a  nerve-muscle  preparation  for  a  short  time, 
the  muscle  responds  only  at  the  make  and  the  break  of  the  current, 
remaining  perfectly  quiescent  all  the  time  the  current  is  passing.  If 
the  nerve  be  in  a  very  excitable  condition,  it  is  possible  that  the  muscle 
may  be  thrown  into  a  tetanus  or  continued  contraction  during  the 
whole  time  that  the  current  is  passing  ('  closing  tetanus  ').     On  the 


THE  EXCITATION  OF  NERVE  FIBRES  297 

other  hand,  if  a  strong  ascending  current  be  passed  through  the  nerve 
for  a  considerable  time,  the  muscle  when  the  current  is  broken  may 
go  into  continued  contraction,  which  may  last  some  time.  Normally, 
however,  the  muscle  simply  responds  with  a  single  twitch  at  the  make 
and  break  of  the  current,  although,  on  investigating  the  condition  of 
the  nerve  during  the  passage  of  the  current,  we  find  that  it  is  consider- 
ably modified.  This  modification  in  the  condition-  of  the  nerve  is 
spoken  of  as  electrotonus,  and  includes  changes  in  its  irritabihty  and 
its  electrical  condition. 

To  investigate  these  changes  the  following  apparatus  is  necessary  : 
two  constant  batteries,  induction-coil,  a  reverser  and  keys,  a  pair  of 


Fig.  114.     Arrangement  of  apparatus  for  showing  electrotonic  changes 

in  irritability. 

e,  exciting  current;  p,  polarising  current;  r,  Pohl's  reverser. 

non-polarisable  electrodes,  and  a  pair  of  ordinary  platinum  electrodes. 
Fig.  114  represents  roughly  the  arrangement  of  the  experiment.  A 
constant  current  from  the  battery  is  led  through  a  part  of  the  nerve 
by  means  of  non-polarisable  electrodes,  which  are  about  one  inch 
apart.  In  this  circuit  we  put  a  reverser,  by  means  of  which  the  direc- 
tion of  the  current  of  the  nerve  may  be  changed  at  will,  and  a  key  to 
make  or  break  the  current.  This  is  the  polarising  circuit.  The  other 
battery  is  arranged  in  the  primary  circuit  of  the  coil,  a  key  being  inter- 
posed, so  that  we  may  use  make  or  break  induction  shocks,  which  are 
applied  to  the  nerve  by  means  of  the  small  platinum  electrodes.  The 
tendon  of  the  muscle  is  connected  by  a  thread  with  a  lever,  which  is 
arranged  to  write  on  a  smoked  surface,  so  that  the  height  of  the  con- 
traction can  be  recorded. 

"We  first  find  the  position  of  the  secondary  coil,  at  which  the  break 
induction  shock  is  a  submaximal  stimulus,  and  we  employ  this 
strength  of  stimulus  throughout  the  experiment.  The  make  induc- 
tion shock  is  prevented  from  acting  on  the  nerve  by  closing  a  short- 
circuiting  key  in  the  circuit  of  the  secondary  coil.     The  nerve  is  now 


298  PHYSIOLOGY 

stimulated  at  various  points  with  a  single  break  induction  shock,  and 
the  contractions  recorded.  The  heights  of  these  contractions  serve 
to  indicate  the  irritability  of  the  nerve  at  the  point  stimulated.  We 
now  throw  the  polarising  current  into  the  nerve.  At  the  make  of  this 
current  the  muscle  will  probably  respond  with  a  twitch  which  is  not 
recorded.  We  then  test  once  more  the  irritability  of  different  points 
of  the  nerve,  and  we  find  that,  when  the  stimulus  is  applied  near  a, 
the  point  where  the  current  enters  the  nerve  (anode),  the  stimulus, 
which  before  gave  a  moderately  large  contraction  of  the  muscle,  now 
has  either  no  effect  or  else  produces  a  very  weak  contraction.  On 
the  other  hand,  in  the  region  of  the  cathode  the  stimulus,  which  before 
was  submaximal,  has  now  become  maximal,  as  is  shown  by  the 
increase  in  the  height  of  the  contraction  evoked  by  the  induction 
shock. 

We  now  reverse  the  direction  of  the  polarising  current,  so  that 
the  current  of  the  nerve  runs  from  k  to  a.  With  this  reversal  of 
current  there  is  also  a  reversal  of  the  changes  in  the  nerve  ;  that  is 
to  say,  the  normally  submaximal  stimulus  is  maximal  when  applied 
near  a,  and  minimal  when  applied  near  k.  On  break  of  the  polaris- 
ing current  the  condition  of  the  nerve  returns  to  normal,  and  the  sub- 
maximal  stimulus  is  once  more  submaximal  throughout. 

This  return  to  normal  conditions,  however,  is  not  immediate,  since  the  first 
effect  of  breaking  the  current  is  a  swing-back,  so  to  speak,  past  the  normal, 
the  diminished  irritability  at  the  anode  gi\ang  place  to  an  increased  irritability, 
which  only  gradually  subsides.  In  the  same  way,  immediately  after  the 
polarising  current  has  ceased  to  flow,  the  neighbourhood  of  the  cathode 
acquires  a  condition  of  diminished  irritability,  and  this  only  gradually  gives 
place  to  a  normal  condition. 

This  experiment  teaches  us  that,  when  a  constant  current  is 
passed  through  a  nerve,  there  is  increase  in  the  irritability  in  the 
nerve  near  the  cathode,  and  a  diminution  in  irritability  near  the  anode. 
These  conditions  of  increased  and  diminished  irritability  are  spoken  of 
as  ratelectrotonus  and  anelectronus  respectively.  In  muscle  we  have 
seen  that  a  make  contraction  always  starts  from  the  cathode,  and  a 
break  contraction  from  the  anode.  Now  the  event  that  takes  place  at 
the  cathode  on  make  and  at  the  anode  on  break  of  a  constant  current 
is,  as  the  last  experiment  shows  us,  a  rise  in  irritability,  in  the  former 
case  from  normal  to  above  normal,  in  the  latter  from  subnormal  to 
normal.  Hence  we  may  say  that  the  excitation  is  caused  by  a  sudden 
rise  of  irritability,  which  may  be  due  either  to  a  sudden  appearance  of 
catelectrotonus,  or  a  sudden  disappearance  of  anelectrotonus.  I  have 
said  suddsn  because  the  steepness  of  the  rise  of  irritability  is  a  neces- 
sary factor  in  causing  excitation.  If  the  polarising  current  passing 
through  a  nerve  be  slowly  and  gradually  increased  to  considerable 


THE  EXCITATION  OF  NERVE  FIBRES  299 

strength,  it  will  give  rise  to  no  contraction.  The  degree  of  suddenness 
of  the  rise,  which  is  most  beneficial  in  causing  contraction,  varies  with 
the  nature  of  the  tissue  stimulated.     Thus  it  is  more  rapid  in  nerve 


Fig.  115.  Diagram  to  show  the  variations  of  irritability  in  a  nerve  during  the  passage 
of  polarising  currents  of  different  strengths.  The  degree  of  change]  is  represented 
by  the  distance  of  the  curves  from  the  base  line ;  the  part  of  the  curve  below 
the  line  signifying  decrease,  that  above  the  line  increase  of  irritability. 

A,  anode  ;  B,  cathode ;  y■^,  effect  of  weak  current ;  y.,,  medium  current ;  y.„  strong 
current.  It  will  bo  noticed  that  the  indifferent  point,  x,  where  the  curve  crosses 
the  horizontal  line,  approaches  nearer  and  nearer  the  cathode  as  the  current  is 
increased  in  strength.     (From  Foster,  after  PflCger.) 

than  in  muscle,  and  in  pale  muscle  than  in  red  muscle,  and  in  voluntary 
muscle  than  in  unstriated  muscle. 

It  is  evident  that  there  must  be,  somewhere  betw^een  the  anode 
and  cathode,  an  indifierent  point — that  is  to  say,  a  region  where  the 
irritability  is  neither  increased  nor  diminished.  We  find  experimentally 


ascendinq   current 


kaTh. 


make  excitation  blocked 
at  anode. 


break  excitation  at  anode 
blocked  at  kathode. 


Fiu.  ll(j.     Diagram  to  show  the  blocking  effect  of  a  strong  constant  current 
passed  through  the  nerve  of  a  nerve-muscle  preparation. 

that  this  indifferent  point  is  nearer  the  anode  when  the  polarising 
current  is  weak,  and  gets  nearer  to  the  cathode  as  the  current  is 
strengthened,  so  that  with  very  strong  currents  nearly  the  whole  intra- 
polar  length  is  in  a  condition*  of  anelectrotonus  (Fig.  115).  When  a 
strong  polarising  current  is  used,  the  depression  of  irritability  at  the 
anode  is  so  marked  that  no  impulse  can  pass  this  region.  Thus  if  we 
send  a  very  strong  ascending  current  through  the  nerve,  there  is  no 
contraction  at  make.  This  is  owing  to  the  fact  that  the  impulse 
started  at  the  cathode  on  make  of  the  current  cannot  reach  the  imiscle, 
its  passage  down  the  nerve  being  blocked  in  the  region  of  the  anode 
(Fig.  IIG,  A). 


300 


PHYSIOLOGY 


The  results  of  stimulating  motor  nerves  by  means  of  constant  currents 
were  studied  bj-  Pfliiger  and,  embodied  in  a  Table,  make  up  what  is  known  as 
Pfliiger's  law.  The  result  of  stimulating  varies  Avith  the  strength  of  a 
current. 

Law  of  Contraction 


strength  of  current 

Ascending 

Descending 

Make                   Break 

Make                 Break 

Weak 

C                           0 

c                    0 

Medium   . 

c                       c 

C                    c 

Strong 

0                  Cor  T 

C  or  T                0 

c  =  contraction.     C  =  strong  contraction.     T  =  tetanus.     O  =  no  eti'ect. 

With  the  weakest  currents  excitation  occurs  only  at  make,  since  a  make- 
stimulus,  i.e.  the  rise  of  catelectrotonus,  is  always  more  effectual  than  a  break- 
stimvdus,  i.e.  the  disappearance  of  anelectrotonus.     With  currents  of  moderate 


Fig.  117.     Arrangement  of  experiment  to  demonstrate  Pfliiger's  law  of  contraction. 


strength  excitation  occiirs  both  at  make  and  break,  being  better  marked  at 
make,  especially  in  the  case  of  descending  currents.  With  very  strong  currents 
we  get  a  contraction  at  make  only  when  the  current  is  descending,  since,  when 
the  current  is  ascending,  the  excitation  started  at  the  cathode  cannot  pass  the 
block  at  the  anode.  For  the  same  reason  a  break  contraction  is  obtained  only 
with  an  ascending  current,  since  at  the  break  of  a  descending  current  there  is 
a  swing-back  of  the  nerve  at  the  cathode  to  a  condition  of  diminished  irrita- 
bility, which  effectuallj^  blocks  the  excitation  started  higher  up  the  nerve  at 
the  anode. 

The  arrangcimcnt  of  the  experiment  for  demonstrating  Pfliiger's  law  is 
shoMii  in  Fig.  117.  The  strength  of  the  current  is  graduated  by  means  of  the 
rheochord,  the  current  being  led  into  the  nerve  by  means  of  non-polarisable 
electrodes.  It  is  extremely  important  in  these  experiments  to  avoid  any 
injury  or  drying  of  the  nerves  at  either  of  the  two  electrodes,  since  the  excita- 
tory effect  either  at  make  or  break  would  be  abolished  by  local  injury. 

These  results,  worked  out  chiefly  on  motor  nerves,  have  been 
confirmed  as  far  as  possible  experimentally  on  sensory  nevf/es,  and  on 


THE  EXCITATION  OF  NERVE  FIBRES  301 

muscle  and  contractile  tissues  generally,  and  probably  hold  good  for 
all  irritable  living  tissues. 

It  is  said  that  an  anelectrotonus  takes  some  time  to  attain  its 
full  height,  and  a  catelectrotonus  reaches  its  maximum  almost  directly 
after  the  current  is  made,  and  that  it  is  on  this  account  that  a  current 
of  very  short  duration  excites  only  at  the  make,  the  break  occurring 
before  the  anelectrotonus  is  deve- 
loped enough  for  its  disappearance 
to  cause  a  stimulus. 

Other  things  being  equal,  a 
current  of  given  strength  causes 
a  stronger  excitation  the  greater 
the  length  of  nerve  that  it  flows 
through.  It  must  be  remem- 
bered, however,  that  the  nerve 
offers  considerable  resistance  to 
the  passage  of  the  current,  and 
so,  to  keep  the  current  constant 
while  increasing  the  length  of 
intrapolar  nerve,  we  must  largely 
increase  the  electromotive  force 
employed. 

A  very  convenient  method  of  show-  ^^^-  '^'^°- 

ing  the  effect  of  the  length  of  intrapolar 

nerve  on  excitation  has  been  suggested  by  Gotch.  The  two  sciatic  nerves  of 
a  frog  are  dissected  out,  one  of  them  being  in  connection  with  the  gastroc- 
nemius. These  are  first  arranged  as  in  Fig.  118.  a,  h,  and  c  are  three  non- 
polarisable  electrodes,  the  terminals  of  a  constant  battery  being  connected  to 
a  and  c.  The  position  of  the  rider  on  the  rheochord  is  then  ascertained  at  which 
make  of  the  current  just  excites  contraction  in  the  muscle  of  nerve  2,  the  current 
in  this  case  passing  from  a  to  &  along  nerve  1,  and  from  &  to  c  along  a  small 
piece  of  nerve  2.  Wo  ^vill  suppose  that  eleven  units  of  current  are  necessary 
to  produce  excitation,  h  is  then  wthdrawTi  and  the  nerve  2  laid  on  a  (Fig.  1 18,  b), 
so  that  the  current  can  now  pass  from  a  to  c  entirely  through  a  long  stretch 
of  nerve  2.  On  again  seeking  the  minimal  stimulus,  it  will  bo  found  that  a 
smaller  current  is  sufficient  to  excite,  contraction  being  obtained  ^v^th  seven 
units.  Since  the  length  of  nerve  traversed,  and  therefore  the  resistance  to  the 
current,  are  the  same  in  both  cases,4t  is  evident  that  a  current  is  more  effective 
the  greater  the  length  of  excited  nerve  that  it  traverses. 

A  nerve  cannot  be  excited  by  currents  passed  transversely  across 
it,  since  in  such  cases  the  anode  and  kathode  lie  so  close  to  one  another 
in  a  nerve-fibril,  as  it  is  traversed  by  a  current,  that  their  effects 
counteract  one  another. 


302 


PHYSIOLOGY 


Electrical  stimuli  as  applied  to  human  nerves 

When  we  attempt  to  apply  the  results  gained  on  frog's  nerves  to 
man,  we  are  met  at  once  by  the  difl&culty  that  we  cannot  dissect  out 
the  nerves  and  apply  stimuli  to  them  directly.  So  usually  unipolar 
excitation  is  used,  one  electrode,  either  anode  or  cathode,  being 
applied  to  the  nerve  to  be  stimulated,  and  the  other  to  some  indifEerent 
point,  such  as  the  back.     It  is  evident  under  these  circumstances  that 

the  current  is  concentrated  as  it  leaves 
the  anode  and  reaches  the  cathode, 
and  diffuses  widely  in  the  body,  seek- 
ing the  lines  of  least  resistance.  Thus 
it  is  impossible  to  get  pure  anodic  or 
cathodic  effects.  If  the  anode  be  ap- 
plied over  the  nerve,  the  current  enters 
by  a  series  of  points  (the  polar  zone), 
and  leaves  by  a  second  series  (the 
peripolar  zone).  The  polar  zone  will 
thus  be  in  the  condition  of  anelectro- 
tonus,  and  the  peripolar  zone  in  that 
of  catelectrotonus.  The  current,  how- 
ever, will  be  more  concentrated  at  the 

polar  than  at  the  peripolar  zone,  and 
Fig.    119.     Electrodes    applied   to  .tp  isx       -n  j        •    „^^ 

the  skin  over  a  nerve-ti-unk.    In    SO  ^he  former  effect  Will  predommate. 

A  the  polar  area  is  anelectrotonic    These  restrictions  in  the  application  of 

__j     xu-     peripolar    catelectro-     ,i  ,  i-    i  ,  ,    ■ 

the  current  cause  slight  apparent  irre- 
gularities in  the  law  of  contraction  as 
tested  on  man. 


and     the 

tonic.  The  former  condition 
therefore  preponderates,  since 
the  current  here  is  more  con- 
centrated. In  B  the  conditions 
are  reversed,  the  polar  zone 
corresponding  in  this  case  to  the 
cathode.     (Waller.) 


In  stimulating  the  nerves  of  man  for  the 
purpose  of  determining  the  conditions  of  the 
different  muscles,  \vc  may  use  either  induced 
currents  (generally  called  faradic  stimulation)  or  the  make  and  break  of  a  battery 
current  (galvanic  stimulation).  It  is  usual  to  employ  the  unipolar  method,  in 
which  one  electrode  is  placed  over  the  nerve  at  the  point  it  is  desired  to  stimulate, 
while  the  other  electrode,  spoken  of  as  the  indiiferent  electrode,  is  applied  to  the 
skin  over  a  wide  area,  generally  at  the  back  of  the  neck.  The  current  is  then  widely 
diffused  as  it  passes  through  the  indifferent  electrode,  but  is  concentrated  as  it 
passes  between  the  skin  and  the  stimulating  electrode.  The  electrodes  are  covered 
with  chamois  leather  moistened  with  salt  solution  in  order  to  diminish  the 
resistance  of  the  skin.  When  it  is  desired  to  stimulate  any  given  muscle,  the 
.stimulating  electrode  is  brought  as  nearly  as  possible  over  the  spot  where  the 
muscle  receives  its  motor  nerve.  These  '  motor  points  '  have  been  mapped 
out,  and  reference  is  generally  made  to  a  diagram  in  determining  the  point 
for  any  given  muscle.  By  reversing  the  current  the  stimulating  electrode 
may  be  made  either  anode  or  cathode.  It  is  found  that  stimulation  occurs 
most  easily  on  closure  of  the  current  when  the  stimulating  electrode  is  the 
cathode;    with    the    greatest    difficultv  when    the    current  is   broken    and  the 


THE  EXCITATION  OF  NERVE  FIBRES  303 

stiinuJating  electrode  is  the  catlu^de.  These  different  contractions  are  generally 
represented  by  capital  letters,  and  the  usual  relationship  is  expressed  by  the 
statement  that  CCC  is  obtained  most  easily,  then  ACC  and  AOC,  and  finally 
COC. 

CCC  =  cathodal  closing  contraction. 

ACC  =  anodal  closing  contraction. 

AOC  =  anodal  opening  contraction. 

COC  =  cathodal  opening  contraction. 

When  the  motor  nerve  to  a  muscle  has  undergone  degeneration  the  muscle 
also  begins  to  degenerate,  and  we  find  certain  alterations  in  its  response  to 
artificial  stimulation.  In  the  first  place,  the  muscle  may  fail  to  respond  to 
induction  shocks,  while  it  may  show  an  increased  irritability  for  galvanic  shocks. 
In  the  second  place,  qualitative  alterations  in  irritability  may  be  present,  so 
that  ACC  may  be  obtained  with  a  smaller  current  than  CCC.  These  alterations 
are  spoken  of  as  the  '  reaction  of  degeneration.' 


SECTION  VI 


t 


THE  CONDITIONS  WHICH  DETERMINE 
ELECTRICAL  STIMULATION 

For  every  tissue  traversed  by  a  current  there  is  a  minimum  rate 
of  change  at  which  the  current  through  the  tissue  must  be  increased 
_  or   diminished  in    order  to   cause    excitation.     If 

instead  of  suddenly  making  and  breaking  the 
current  passing  through  an  irritable  structure  we 
carry  out  the  change  gradually,  no  excitatory 
efEect  is  produced,  even  although  the  current  may 
finally  attain  a  considerable  strength.  This  fact 
may  be  demonstrated  by  the  use  of  an  apparatus 
known  as  the  rheonome. 

A  useful  form  of  rheonome  is  that  devised  by  Lucas 
(Fig.  120).  Two  zinc  plates  D  and  E,  immersed  in  a 
saturated  solution  of  zinc  sulphate  contained  in  a  rect- 
angular cell,  are  separated  from  one  another  by  a  vulcanite 
diaphragm.  In  the  diaphi-agm  is  a  hole  G  by  which  the 
two  sides  of  the  vessels  are  connected.  This  hole  can  be 
closed  at  any  desired  rate  by  a  shutter  F.  When  the 
hole  is  closed  no  current  can  pass  between  the  plates, 
and  the  amount  which  can  pass  will  depend  on  the 
extent  to  which  the  shutter  has  been  raised.  By  givmg 
the  hole  the  right  shape  it  is  possible  to  diminish  the 
resistance  of  the  apparatus  regularly.  If  this  rheonome 
be  placed  in  circuit  with  a  battery  and  an  excitable 
tissue,  such  as  the  nerve  of  a  nerve-muscle  preparation, 
we  can  make  a  current  or  break  a  current  through  the 
tissue  at  any  desired  rate.  Thus  the  course  of  the  current 
through  the  tissue  will  be  represented,  not  by  a  vertical 
line,  but  by  a  sloping  hne  which  may  be  given  any 
desired  degree  of  steepness  (Fig.  121). 

If  the  current  be  slowly  increased  through  the 
nerve  or  be  slowly  cut  off  from  the  nerve,  no 
excitatory  efEect  takes  place,  while  quickly  opening  or  closing  the 
shutter  will  cause  excitation.  It  might  be  concluded  that  the 
excitatory  efEect  of  a  current  increases  with 

1.  The  intensity  of  the  current. 

2.  The  rate  of  change  of  the  current. 

The  second  of  these  conditions  needs,  however,  some  correction, 

304 


Fig.  120. 
Rheonome  of 
Keith  Lucas. 


ELECTRICAL  STIMULATION 


305 


As  we  increase  the  rate  of  change  of  current,  by  employing  in  the  case 
of  induced  currents  more  and  more  rapid  alternations,  we  find  that  the 
excitatory  efEect,  instead  of  increasing,  Jsegins  to  diminish  and  finally 
disappears,  so  that  high-frequency  currents  of  enormous  tension  can, 
as  in  Tesla's  experiments,  be  led  through  the  body  without  any 
apparent  physiological  efEect.  On  the  other  hand,  by  using  more 
sluggish  forms  of  irritable  tissue,  we  may  find  that  even  induction 
shocks  are  too  rapid  for  effective  excitation.  Thus  the  red  muscles  of 
the  slow-moving  tortoise  react  better  to  the  slow  make  than  to  the 
sudden  break  induction  shock,  and  iaany  forms  of  unstriated  muscle 
are  unaffected  by  either  make  or  break  shock.  There  is  in  fact  for  each 
tissue  an  optimum  rate  of  change  varying  with  the  character  of  the 
tissue,  at  which  the  current  necessary  to  produce  a  response  is  at  a 
minimum.  This  optimum  rate  of  change  is  spoken  of  by  Waller  as  the 
'  characteristic  '  of  an  irritable  tissue. 


Fig.  121.  >Stnng  galvanometer  records  of  the  chcinge  of  current  obtained  by 
opening  the  diaphragm  in  the  rheonome  (Fig.  120)  at  different  rates. 
(K.  Lucas.) 

A  further  investigation  of  the  time  relations  of  electrical  stimuli 
by  Keith  Lucas  has  thrown  important  light  on  the  character  of  the 
excitatory  response  itself.  The  difference  between  various  excitable 
tissues  is  perhaps  best  brought  out  by  finding  the  minimum  strength 
of  current  which  will  excite  at  make  and  then  determining  how  much 
this  current  must  be  increased  when  it  is  broken  at  a  very  short 
interval  of  time  after  it  has  been  made.  The  following  Table  represents 
the  relation  between  duration  and  strength  of  current  necessary  to 
stimulate  in  the  case  of  the  sciatic  nerve  of  the  toad  : 


Duration  of  current  (sec.) 

CO 

•0070 
•0035 
•00087 
•00043 


Strength  of  current  (volts) 
•086 
•091 
•119 
•179 
•245 


If  we  shghtly  alter  the  use  by  Waller  of  the  word  '  characteristic  ' 
we  may  take  as  the  characteristic  of  the  tissue  the  duration  of  the 
stimulus  at  which  the  current  necessary  to  stimulate  was  just  double 
the  minimum.  ^  In  this  case  the  minimal  stimulating  current  was 
approximately    doubled    when    the    duration    of    the    current    was 

20 


306  PHYSIOLOGY 

limited  to  about  •001  sec.  From  a  number  of  experiments  of  this 
description  Lucas  gives  the  following  as  the  characteristic,  or  what 
he  terms  the  "  excitation  times,"  of  muscle  and  of  nerve  : 

Muscle -017      sec. 

Nerve  fibre -003       „ 

Nerve-ending  (or  intermediary  substance)  "00005   ,, 

Similar  differences  are  obtained  when  we  attempt  to  determine 
by  means  of  the  rheonome  the  minimal  gradient  of  current  necessary 
to  excite  a  nerve.  In  the  case  of  the  toad's  nerve  the  minimal  gradient 
must  be  ten  times  as  steep  as  in  the  case  of  the  toad's  muscle,  and  is 
such  that  in  one  second  the  current  must  reach  a  strength  forty-five 
times  the  minimal  strength  which  is  necessary  to  excite  when  the 
current  is  made  instantaneously.  In  the  frog's  nerve  the  minimal 
gradient  is  still  steeper,  so  that  in  one  second  the  current  must  reach 
sixty  times  the  strength  of  the  minimal  exciting  current.  We  may 
interpret  these  results  as  signifying  that  the  excitatory  state  pro- 
duced in  an  irritable  tissue  involves  the  production  of  some  change 
which  passes  away  spontaneously.  The  rate  of  production  of  the 
change,  and  still  more  the  rate  of  its  spontaneous  disappearance,  differ 
from  tissue  to  tissue.  If  the  gradient  of  a  current  which  is  made 
through  the  tissue  is  too  slight,  the  spontaneous  disappearance  of  the 
excitatory  change  goes  on  as  rapidly  as  the  production  in  consequence 
of  the  rise  of  current.  No  excitation  therefore  takes  place.  The 
"  excitation  time  "  of  the  tissue  will  thus  be  proportional  to  the 
duration  of  the  excitatory  change  produced  in  the  tissue  as  a  result 
of  the  stimulus.  We  may  compare  the  excitation  time  of  three 
tissues  with  the  duration  of  the  electrical  change  produced  in  the 
same  tissues  by  a  single  stimulus. 

The  excitation  times  were  : 

Frog's  nerve  fibre "003  sec. 

Muscle  fibre  of  sartorius    .        .        .        .     'OlT     ,, 
Ventricular  muscle  of  frog        .        .        .  2 "000     ,, 

In  the  case  of  muscle,  according  to  Burdon  Sanderson,  the  electrical 
change  reaches  its  culminating-point  in  "0025  sec,  and  may  take 
perhaps  eight  times  this  interval  before  it  dies  away.  In  the  cardiac 
muscle  of  the  tortoise  Sanderson  found  the  electrical  change  to  last 
between  two  and  three  seconds. 

SUMMATIO  ;  OF  STIMULI.  Closely  associated  with  the  excita- 
tion time  of  the  tissues  are  the  phenomena  of  '  summation  of 
stimuU '  and  *  refractory  period.'  If  two  subminimal  stimuli  are 
sent  in  within  a  sufficiently  short  interval  of  time,  their  effect  is 
summated,  so  that  two  stimuli,  each  of  which  would  be  ineffective, 


ELECTRICAL  STIMULATION  307 

may  together  produce  an  excitation.  In  the  case  of  striated  muscleS; 
in  order  that  mechanical  summation  of  contraction  may  take 
place,  the  second  stimulus  must  become  effective  before  the  muscle 
has  completely  relaxed ;  the  second  contraction,  that  is  to  say, 
starts  from  the  height  to  which  the  first  contraction  has  brought 
the  muscle.  A  similar  condition  of  things  appears  to  hold  for  summa- 
tion of  stimuli,  if  we  substitute  for  mechanical  change  in  muscle  the 
molecular  change  which  accompanies  the  excitatory  state.  For 
summation  of  two  stimuli  to  take  place,  the  second  stimulus  must 
occur  at  a  time  before  the  condition  excited  by  the  first  stimulus  has 
passed  away.  The  maximum  time  at  which  summation  of  two 
stimuli  can  take  place  will  therefore  vary  from  tissue  to  tissue  and 
will  bear  a  relation  to  what  we  have  designated  the  '  excitation  time  ' 
of  the  tissue  and  also  to  the  rapidity  of  current  gradient  necessary 
to  excite  the  tissue.  This  will  be  evident  if  we  compare  the  maximum 
summation  intervals  for  different  tissues  with  the  excitation  time  of  the 
same  tissues. 

stimulating  current  5     above  minimal  stimulus 


Summation  interval 

I'E: 

scitation  time  " 

sec. 

sec. 

Prog's  nerve 

•0005 

•003 

„       sartorius 

•0015 

•017 

„       heart 

•0080 

2-000 

REFRACTORY  PERIOD.  The  phenomenon  of  a  refractory  period 
has  long  been  known  in  connection  with  the  heart  muscle  and  has 
often  been  regarded  as  characteristic  of  tliis  muscle.  If,  in  the 
isolated  ventricle,  a  beat  be  evoked  by  a  single  minimal  stimulus, 
subsequent  repetition  of  the  stimulus  during  the  course  of  the 
contraction  is  ineffective,  and  becomes  efiectis^e  only  when  the 
contraction  has  passed  away.  The  heart  is  said  to  be  refractory  to 
stimuli  during  this  period.  The  duration  of  the  refractory  period  is 
a  question  of  the  strength  of  the  stimulus  used.  With  strong  stimuli 
the  heart  may  be  made  to  contract  when  the  relaxation  has  only  pro- 
gressed half  way,  and  with  very  strong  stimuli  one  contraction  may 
be  made  to  follow  the  last  at  such  a  shoH  interval  that  hardly  any 
trace  of  relaxation  is  observable  between  the  beats.  The  phenomenon 
seems  to  be  common  to  all  excitable  tissues.  Thus  if  two  stimuh  are 
applied  to  a  nerve  within  a  sufficiently  brief  interval,  the  second 
stimulus  is  ineffective,  so  far  as  can  be  determined  by  the  response  of  an 
attached  muscle  or  by  means  of  a  capillary  electrometer.  The  period 
is  longer  the  lower  the  temperature  and  varies  from  -0006  sec.  at 
40°  C.  to  -002  sec.  at  12°  C.  This  critical  interval  is  lengthened  if  the 
irritabihty  of  the  nerve  is  depressed  by  narcotics.  We  may  ascribe  it  to 
the  second  stimulus  being  applied  before  the  excitatory  change  due  to 


308 


PHYSIOLOGY 


the  first  stimulus  has  reached  its  culminating- point.  If  the  first 
stimulus  was  maximal  it  is  evident  that  no  further  addition  to  the 
molecular  change  could  occur  as  a  result  of  the  incidence  of  the  second 
stimulus. 

THE  EFFECT  OF  TEMPERATURE  ON  EXCITABILITY.  It  was 
found  by  Gotch  that  the  excitability  of  a  nerve  within  certain 
limits  was  increased  by  cooling  the  nerve  and  diminished  by  raising 
its  temperature  (Fig.  122).  Thus,  if  a  frog  be  cooled  to  2^  C.  or  3°  C. 
for  a  day,  it  will  be  found  that  simple  section  of  the  sciatic  nerve 
may  suffice  to  send  the  gastrocnemius  into  continued  contraction, 
and  under  these  circumstances  '  closing  tetanus  '  may  be  obtained 
with  the  greatest  ease.  This  increase  of  excitability  does  not  apply 
to  all  kinds  of  stimuli.  In  the  case  of  nerve  its  irritability  was 
found   to   be  increased  by  warming,  and  diminished  by  cooling  for 


Fig.  122.  Tracing  of  muscle  contractions  to  show  effect  of  cooling  a  nerve 
on  its  excitability.  The  lower  line  indicates  the  changes  in  temperature 
of  the  excited  part  of  the  nerve.  The  muscle  responded  only  when  the 
nerve  was  cooled,  the  stimulus  becoming  ineffectual  when  the  nerve 
was  warmed.     (Gotch.) 

induction  shocks  and  for  all  galvanic  currents  of  less  duration  than 
•005  sec.  In  skeletal  muscle  Gotch  found  the  excitability  for  all 
forms  of  stimuli  increased  by  cooling.  Lucas  has  shown  that 
these  paradoxical  effects  in  nerve,  namely,  increase  of  excitability 
towards  currents  of  long  duration  and  the  simultaneous  decrease 
towards  currents  of  short  duration,  are  conditioned  by  two  opposed 
changes  in  the  tissue.  The  fall  of  temperature  delays  the  subsidence 
of  the  excitatory  process,  but  at  the  same  time  renders  more  difficult 
the  initiation  of  a  propagated  disturbance.  The  first  of  these  effects 
reduces  the  current  required  for  excitation  in  a  ratio  which  is  greater 
the  greater  the  duration  of  the  current.  The  latter  increases  the  current 
required  in  the  same  ratio  for  all  durations.  If  then  the  change  of 
temperature  is  such  that  the  two  opposite  effects  are  exactly  balanced 
at  a  certain  medium  duration  of  current,  it  follows  that  for  currents 


ELECTRK.^AL  STIMULATION  309 

of  longer  duration  the  net  result  will  be  to  reduce  the  current  required 
for  excitation,  while  for  currents  of  shorter  duration  the  net  result 
will  be  to  increase  the  current  required.  The  effect  of  temperature 
therefore  on  the  minimum  exciting  current  will  vary  from  tissue  to 
tissue  according;  as  the  two  factors,  rate  of  subsidence  of  excitatory 
change  and  the  initiation  of  a  propagated  disturbance  as  a  result  of  the 
excitatory  change,  are  relatively  affected  by  change  of  temperature. 

THE  EFFECT  OF  INJURY.  The  irritability  of  the  nerve  of  a 
muscle-nerve  preparation  is  not  equal  in  all  parts  of  its  course,  but 
is  greater  at  the  upper  end,  probably  in  consequence  of  the  proximity 
of  the  cross-section. 

Some  time  after  a  motor  nerve  is  divided  the  increased  irritability 
at  the  upper  end  gives  way  to  a  decreased  irritability,  and  this  decrease 
goes  on  till  the  nerve  is  no  longer  excitable.  The  diminution  in 
excitability  gradually  extends  down  the  nerve  fibre,  so  that  the  part 
of  the  nerve  nearest  the  muscle  remains  excitable  the  longest.  This 
progressive  change  in  the  irritability  of  a  nerve  after  section  is  spoken 
of  as  the  Ritter- Valh  law.  It  is  soon  followed  by  definite  1  istological 
changes  in  the  nerve,  which  we  shall  describe  later. 


SECTION  VII 


THE  NEURO-MUSCULAR  JUNCTION 

The  excitatory  process  travelling  down  a  motor  nerve  has  to  be 
transmitted  to  the  muscle  by  the  intermediation  of  the  nerve- ending 
or  end-plate.  We  have  learnt  to  regard  the  axis  cyhnder  as  the  seat 
of  the  propagated  excitatory  process.  In  the  end-plate,  however,  the 
axis  cylinder  comes  to  an  end.  When  stained  by  methylene  blue 
or  by  impregnation  with  chromate  of  silver  or  mercury,  the  axis 
cylinder,  after  passing  through  the  sarcolemma 
of  the  muscle  fibre,  is  seen  to  break  up  into  a 
number  of  branches  (in  some  cases  forming  a 
typical  end- arborisation),  which  lie  on  or  are 
embedded  in  a  small  amount  of  undifferentiated 
nen/e  protoplasm  containing  nuclei  (the  '  sole  plate  '). 
A  similar  break  in  structural  continuity  seems 
to  occur  in  the  central  nervous  system  wherever 
an  impulse  is  propagated  from  the  axon  process 
of  one  nerve-cell  to  the  body  or  dendrites  of 
another  nerve-cell.  The  end-processes  of  the 
axon  come  in  contact  with  the  next  member 
in  the  chain  of  neurons,  but  no  anatomical 
continuity  is  to  be  made  out,  at  any  rate  in 
the  higher  animals.  In  the  central  nervous 
system  the  area  of  contiguity,  where  an  im- 
pulse passes  from  one  neuron  to  another,  is 
spoken  of  as  a  synapse.  The  presence  of  the 
synapse,  or  end-plate,  between  muscle  and  nerve  imposes  certain  new 
conditions  on  the  conduction  of  the  excitatory  impulse.  One  of  the 
most  important  of  these  lies  in  the  fact  that  the  conduction  across  the 
end-plate,  and  probably  across  the  synapse  of  the  central  nervous 
system,  is  ineci-procal.  An  excitatory  process  started  in  the  nerve 
travels  easily  across  the  end- plate  to  the  muscle.  On  the  other  hand, 
an  excitatory  process  started  in  the  muscle  does  not  extend  through 
the  end-plate  to  the  nerve  fibre.  This  fact  may  be  shown  on  the  frog's 
sartorius.  If  the  lower  tibial  end  of  the  muscle  be  split,  as  in  Fig. 
123,  a  mechanical  stimulus,  such  as  a  snip  with  the  scissors,  applied 
to  the  lower  nerve-free  end  of  one   of  the  hmbs,  e.g.  at  a,  causes  a 

310 


THE  NEURO-MUSCULAR  JUNCTION  311 

contraction  of  the  corresponding  half  of  the  muscle,  which  does  not 
extend  to  the  other  half.  On  snipping  the  muscle  a  little  higher  up 
at  B,  where  nerve-endings  are  present,  the  resulting  contraction  involves 
the  whole  of  the  muscle,  owing  to  the  fact  that  the  excitation  started 
in  the  nerve-endings  spreads  in  both  directions  through  the  branching 
nerve  fibres.  It  is  possible  that  this  irreciprocity  of  conduction  may 
be  of  comparatively  late  appearance  in  evolution.  So  far  as  we  know, 
an  excitatory  process  in  a  sheet  of  muscle  and  nerve  fibres,  such  as  we 
find  in  lower  invertebrata,  e.g.  in  medusa,  may  travel  with  equal 
facility  in  all  directions.  We  are  probably  not  warranted  from  our 
experiments  on  skeletal  muscle  in  concluding  that  the  contraction  of 
a  cardiac  muscle-cell  may  not  set  up  an  excitatory  process  in  the 
sm-rounding  network  of  nerve  fibres.  It  is  impossible,  however,  to 
put  such  a  suggestion  to  experimental  test,  since  in  the  heart,  there  is 
no  portion  of  muscle  fibre  sufficiently  removed  from  nerves  to  allow  of 
an  excitation  being  applied  which  might  not  at  the  same  time  affect  the 
nerve  fibres. 

There  is  evidence  that  the  transmission  of  the  excitatory  condition 
across  the  end- plate,  from  nerve  to  muscle,  involves  a  special  excitatory 
process  and  the  expenditure  of  energy.  Thus  there  is  a  period  of  delay 
between  the  arrival  of  an  excitatory  impulse  at  the  terminations  of 
the  motor  nerve  and  the  beginning  of  the  electrical  change  which 
marks  the  moment  of  stimulation  of  the  muscle  fibre.  If  we  compare 
the  latent  period  of  a  muscle  stimulated  directly  with  its  latent  period 
w^hen  excited  through  the  nerve,  we  find  that  there  is  an  increased 
period  of  delay  in  the  latter  which  is  not  wholly  accounted  for  bv  the 
time  taken  for  the  impulse  to  travel  from  the  stimulated  spot  down  the 
nerve  fibres  to  the  muscle.  The  extra  delay  is  due  to  the  processes 
occurring  in  the  end-plate.  This  end-plate  delay  has  been  found  to 
amount  to  -0013  sec.  We  may  take  it  roughly  at  a  thousandth 
of  a  second.  The  end- plate  seems  to  be  the  weakest  point  in  the  neuro- 
muscular chain.  We  have  already  seen  that,  when  ,a  nerve  of  a 
nerve-muscle  preparation  is  stimulated  repeatedly,  the  muscle  very 
soon  shows  signs  of  fatigue,  and  that  the  seat  of  this  fatigue  is  not  in 
the  nerve,  nor  in  the  muscle,  but  in  the  end-plate. 

It  has  been  suggested  that  the  excitation  of  muscle  through  nerve 
depends  on  an  electrical  change  or  discharge  at  the  nerve-ending. 
This  discharge  must  originate  in  the  terminations  of  the  axon  and 
must  influence,  in  the  first  instance,  the  substance  which  forms  the 
intermediary  between  the  axon  and  the  contractile  material  of  the 
muscle.  We  have  indeed  direct  evidence  of  the  existence  of  a  third 
substance,  neither  nerve  nor  muscle,  at  the  point  of  junction  of  these 
two  tissues.  Thus,  curare  is  generally  said  to  paralyse  the  end- 
plates.      Evidence     for    this      statement    has    been    given    in    the 


312  PHYSIOLOGY 

previous  chapter.  Kiiline  has  shown  that  when  the  irritabihty  of 
the  frog's  sartorius  is  tested  at  different  points  it  is  greater  in  the 
situation  of  the  end-plates.  This  might  be  ascribed  to  the  presence 
of  the  more  irritable  nerve-fibres  passing  into  the  muscle-fibres  at 
these  points.  The  unequal  distribution  of  irritabihty  is  not,  however, 
changed  when  the  muscle  is  fully  poisoned  with  curare,  so  as  to 
block  entirely  the  passage  of  any  impulse  from  the  nerve  to  the  muscle. 
We  must  therefore  regard  curare  as  acting,  not  on  the  axon  terminations, 
but  on  the  substance  intervening  between  these  terminations  and  the 
contractile  substance  of  the  muscle.  Additional  evidence  of  the 
existence  of  such  a  "  receptor  "  substance,  as  he  calls  it,  has  been 
furnished  by  Langley.  Nicotine  resembles  curare  in  blocking  the 
passage  of  impulses  from  the  motor  nerve  to  skeletal  muscle,  though 
inferior  to  curare  in  this  respect.  If  4  mg.  of  nicotine  be  injected 
into  the  vein  of  an  anaesthetised  fowl,  the  hind  limbs  become  gradually 
stiff  and  extended  in  consequence  of  a  tonic  contraction  of  all  their 
muscles.  The  effect  slowly  passes  off,  but  can  be  reinduced  by  a 
second  dose  of  nicotine.  It  is  worthy  of  note  that  the  stimulating 
effect  of  nicotine  occurs  even  when  sufficient  is  given  entirely  to  paralyse 
the  motor  nerves.  It  might  be  thought  that  the  stimulating  effect  of 
nicotine  was  a  direct  one  upon  the  muscle  fibre,  but  experiment  shows 
that  curare  has  a  marked  antagonising  action  on  the  contraction  pro- 
duced by  nicotine.  A  sufficient  dose  of  curare  annuls  the  contraction 
produced  by  a  small  amount  of  nicotine  and  diminishes  that  caused  by 
a  large  amount.  The  point  of  action  of  the  nicotine  must  therefore  be 
the  same  as  that  of  the  curare.  After  a  muscle  has  been  relaxed  by 
curare  it  can  be  still  made  to  contract  by  direct  stimulation.  On  the 
other  hand,  nicotine  will  produce  its  stimulating  effect  when  injected 
into  a  bird  in  which  degeneration  of  all  the  nerve  fibres  of  the  muscle 
has  been  produced  by  previous  section  of  the  nerve-trunks.  It  is 
evident  therefore  that  nicotine,  like  curare,  acts,  not  on  the  axon 
terminations,  but  on  a  receptor  substance,  an  intermediary  substance 
intervening  between  the  axon  terminations  and  the  contractile  sub- 
stance of  the  muscle. 

Evidence  in  favour  of  such  an  intermediary  substance  has  been 
brought  by  Keith  Lucas  from  an  entirely  different  standpoint.  In 
determining  the  optimal  electrical  stimuli  or  the  '  characteristic  '  of 
muscle  and  nerve  by  the  condenser  method  {v.  p.  305),  Lucas  finds  that, 
even  after  moderate  doses  of  curare  sufficient  to  abolish  the  possibility 
of  excitation  through  the  nerve-trunk,  the  muscles  show  two  optimal 
stimuli,  pointing  to  the  existence  in  them  of  two  excitatory  substances, 
one  of  which  is  not  paralysed  by  moderate  doses  of  curare.  This 
result  was  confirmed  when  the  tissue  was  investigated  by  determining 
the  relation  of  current  duration    to    the  liminal  current  strength 


THE  NEURO-MUSCULAR  JUNCTION 


313 


necessary  to  excite.  In  a  normal  sartorius  he  finds  three  substances, 
each  distiniiuished  by  its  own  '  excitation  time.'  In  the  pelvic 
nerve-free  end  of  the  sartorius  there  is  only  one  substance,  with  an 
excitation  time  of  -017  sec.  This  may  be  regarded  as  the  miLscle 
substance  proper.  In  the  sciatic  nerve-trunk  there  is  a  second  sub- 
stance with  a  much  steeper  characteristic  and  with  an  excitation 
time  of  -(XJS  sec.  On  experimenting  on  the  middle  region  of  the 
sartorius  we  find  not  only  these  two  substances  but  a  third  substance, 
which  Lucas  calls  the  substance  /3,  with  an  extremely  rapid  excita- 
tory process.  Its  excitation  time  is  •00CO5  sec.  The  presence  of 
these  three  substances  in  the  middle  part  of  the  toad's  sartorius  is 
shown  in  the  diagrams    (Fig.   124),  which    represent   the  relation  of 


V--f3 

-  Vi. 

^v,,^ 

o. 

.  ..i.i..i.> 

,  1  ,  , 

Fig.   124. 


strength  to  duration  of  the  currents  necessary  to  evoke  a  contrac- 
tion. In  this  curve  a  represents  the  muscle  material,  y  the  nerve 
material,  and  /5  the  curve  of  the  intermediary  substance. 

Similar  conditions  are  found  in  the  visceral  neuro- muscular  system. 
Here  the  nerve  fibres  leaving  the  central  nervous  system  do  not  pass 
direct  to  the  muscle  fibres,  but  end  in  arborisations  round  ganglion- 
cells,  which  are  collected  to  form  the  ganglia  of  the  sympathetic  chain 
or  gangha  situated  more  peripherally  and  nearer  the  reacting  tissue. 
Relays  of  fibres,  for  the  most  part  non-medullated,  arise  from  these 
ganglion-cells  and  pass  to  the  unstriated  muscles  of  the  blood-vessels 
and  viscera,  where  they  end  in  plexuses  or  networks  among  the  muscle 
fibres,  possibly  connected  by  short  branches  with  the  fusiform  muscle 
fibres  themselves.  No  structure  is  present  at  the  periphery  exactly 
analogous  to  the  end- plate,  and  it  is  possible  that,  as  Elliott  suggests, 
the  end-plate  is  really  homologous  with  the  whole  of  the  svmpathetic 
ganglion  with  its  post- ganglionic  fibres  passing  to  the  visceral  muscles. 


314  PHYSIOLOGY 

At  any  rate,  the  action  of  curare  and  of  nicotine  on  these  peripheral 
ganglia  is  very  similar  to  their  action  on  the  skeletal  end- plates, 
nicotine,  however,  having  a  relatively  stronger  action  than  curare. 
Injection  of  nicotine  stimulates  and  then  paralyses  the  peripheral  nerve- 
cells  of  the  visceral  system  ;  curare  in  sufficiently  large  doses  para- 
lyses them.  More  instructive  in  relation  to  the  presence  of  receptor 
substances  is  the  action  of  adrenalin.  This  substance,  which  is  pro- 
duced by  the  medulla  of  the  suprarenal  glands,  has  a  specific  action 
on  all  tissues  innervated  by  the  sympathetic  system.  It  causes  almost 
universal  constriction  of  the  blood-vessels,  dilatation  of  the  pupil, 
acceleration  of  the  heart,  and  inhibition  of  the  intestinal  muscles,  with 
the  exception  of  the  ileo-colic  sphincter,  which  it  causes  to  contract, 
all  of  which  efiects  can  also  be  produced  by  stimulation  of  branches 
of  the  sympathetic  nerve.  On  the  other  hand,  tissues  which 
are  not  innervated  from  the  sympathetic,  such  as  the  blood-vessels 
of  the  lungs,  are  unaffected  by  the  drug.  This  fact,  together  with  the 
opposite  effects  of  adrenalin  on  different  unstriated  muscles,  shows 
that  its  action  cannot  be  a  direct  one  on  muscle-fibre.  It  presents  a 
marked  contrast,  for  instance,  to  barium  salts,  which  produce  a  con- 
traction of  every  unstriated  muscle-fibre  in  the  body.  On  the  other 
hand,  we  cannot  ascribe  this  action  to  a  stimulation  of  the  sympathetic 
nerve-endings,  since  adrenalines  equally  effective  if  applied  after  the 
whole  ot  these  nerve-endings  have  been  made  to  degenerate  by  section 
of  the  post-ganglionic  sympathetic  nerve-trunks.  Its  action  therefore 
must  lie  a.t  the  junction  between  nerve  and  muscle,  and  must  be  on 
some  intermediate  or  receptor  substance  developed  at  the  myoneural 
junction,  and  having  for  its  function  the  transference  of  the  excitatory 
process  from  the  nerve  fibre  to  the  contractile  substance  of  the  muscle 
fibre.  Similar  receptor  substances  may  act  as  intermediaries  in 
every  case  of  propagation  of  an  impulse  across  a  synapse  of  whatever 
description,  and  may  by  their  properties  determine  the  peculiar 
qualities  of  the  synapse.  We  may  compare  them  to  the  fulminating 
cap  which  in  a  shell  is  used  to  transfer  the  process  of  combustion  from 
the  slow-match  to  the  bursting  charge.  Their  existence  is  of  especial 
importance  when  we  endeavour  to  investigate  the  mode  of  action  of 
drugs.  It  is  probable  that  they  will  be  found  to  play  a  great  part  in 
determining  the  differential  action  of  drugs  on  various  tissues  in  the 
bodv. 


SECTION  VIII 

POLARISATION  PHENOMENA  IN  NERVE 

ELECTROTONIC  CURRENT.  If  a  constant  current  be  passed 
through  a  nerve  fibre  through  the  electrodes  x  and~  ?/ — <r^  being 
the  anode  and  y  the  cathode — and  the  extrapolar  portions  of  the 
nerve  ah,  cd  be  connected  with  galvanometers,  the  needles  of  both 
are  deflected,  and  the  direction  of  the  deflection  shows  the  existence 
of  a  current  in  the  extrapolar  portions  of  the  nerve  a  to  6,  and 
from  do  d. 


a  ^^-.4— 


t     1 


t     I 


> 


G'  •  G2 

Fig.  125.     Diagram  showing  electrotonic  currents,     r,  polarising  circuit 
G^,  g2,  galvanometers. 


The  galvanoinoters  will  indicate,  before  the  passage  of  the  polarising  current, 
the  ordinary  demarcation  current  of  the  nerve  resulting  from  tlie  cross-section 
at  the  upper  end.  This  current  flows,  in  the  outer  circuit,  from  equator  to  cujj 
end,  and  therefore  in  the  nerve-fibre  from  a  to  b,  and  from  d  to  c.  The 
effect  of  closing  the  polarising  currerit  will  be  to  increase  ^he  current  of  rest 
between  a  and  b,  and  to  diminish  that-between  c  and  d. 

We  thus  see  that  the  passage  of  a  current  through  a  part  of  a 
nerve  gives  rise  to  a  current  flowing  through  a  considerable  portion 
of  the  nerve  fibre  on  each  side  of  tlic  polarising  ciu"rent  and  in  the 
same  direction.  This  ciu-rent  is  called  the  electrotonic  current.  It 
must  not  be  confounded  with  the  current  of  action,  which  originates 
at  one  of  the  poles,  only  at  make  or  break  of  the  current,  and  is  trans- 
mitted thence  in  the  form  of  a  wave  with  a  measmable  velocity  (in  the 
frog)  of   about  30  metres  per  second.     The  electrotonic  current  is 

315 


316  PHYSIOLOGY 

developed  instantaneously,  and  lasts  the  whole  time  that  the  current 
is  flowing  through  the  nerve.  Its  production  is  dependent  on  the 
occurrence  of  polarisation  between  the  sheath  and  the  conducting  part  of 
the  nerve  fibre  and  may  be  exactly  reproduced  on  a  model  consisting 
of  a  core  of  zinc  or  platinum  wire  in  a  casing  of  cotton  soaked  with 
ordinary  salt  solution.  Although  thus  physical  in  origin,  its  produc- 
tion is  dependent  on  the  vitality  of  the  nerve,  and  so  is  not  to  be  con- 
founded with  the  simple  spread  of  current. 


Glass  tube 

containing  0-6%  Na  CI. 

Pt.wire 


Fig.  12G.     Apparatus  for  imitating  the  polarisation  phenomena  in  medul- 
lated  nerve  ('  Kernleiter  '  model). 

The  polarisation  phenomena  resulting  from  the  passage  of  a 
constant  current  through  a  medullated  nerve  can  be  studied  on  a 
model  made  up  of  a  glass  tube  filled  with  normal  salt  solution,  con- 
taining a  platinum  or  zinc  wire  stretched  through  it  (Fig.  126).  On 
leading  a  current  through  a  ^d  6,^and  connecting  c  and  d  with  a 
galvanometer,  a  current  ^vill  be  observed  in  the  extrapolar  portion  of 
the  model  in  the  same  direction  as  in  the  intrapolar.  That  this  spread 
of  current  is  due  to  polarisation  is  shown  by  the  fact  that,  if  the  model 


-ill 

iii+ 

♦  - .  -  + 
♦    -     ♦  - 

+ 

-%-**-*-; 

=  -=  Z.-Z.^-^-L. 

=,:.-_- 

-"_"" 

"  -  -'-'-  .-_---_  -"— ~:  ;_ 

'Sz  -  's~  T  '^.  3  F.-  .-_ 

•i^-J-,. 

C 

b         a 

d        e        f 

Fig.  127.     Diagram  to  show  polarisation  at  the  surface  between  conducting 
core  and  electrolyte  sheath  in  a  '  Kernleiter.^ 


be  made  of  zinc  wire  immersed  in  saturated  zinc  sulphate  solution, 
so  that  no  polarisation  can  occur,  the  spread  of  current  to  the  extrapolar 
area  is  also  wanting.  If  we  examine  the  phenomena  taking  place  at  the 
anode,  we  see  that  a  current  passes  here  through  an  electrolyte  to  the 
conducting  core.  Every  passage  of  a  current  through  an  electrolyte 
must  be  accompanied  by  dissociation,  the  current  being  carried 
by  the  ions.  We  get  therefore  a  movement  of  negative  ions  up  into 
the  electrode,  and  a  deposition  of  electropositive  ions  on  the  core 
(Fig.  127,  a).  In  the  same  way  at  the  cathode  there  will  be  a  deposit 
of  electronegative  ions  on  the  core  (Fig.  127,  d),  so  we  may  say  that 


POLARISATION  PHENOMENA  IN  NER\T^  317 

the  core  is  positively  polarised  at  the  anode  and  negatively  polarised 
at  the  cathode.  This  polarisation,  while  opposing  the  primary  current, 
will  set  up  currents  in  the  suiTOunding  electrolytic  sheath,  as  shown  by 
the  arrows  in  Fig.  128,  the  current  passing  from  a  to  6  and  from  6  to  c  in 
the  electrolyte,  returning  towards  a  in  the  core.  Hence  if  we  lead  ofi 
from  the  sheath  in  the  neighbourhood  of  the  anode  from  a  and  c,  a 
current  will  pass  in  the  galvanometer  from  a  to  c,  that  is,  along  the 
core  in  the  same  direction  as  the  intrapolar  cm"rent.     The  same  factors 


Fig.  128.     Diagram  to  show  polarisation  curreuts  in  a  '  Kernleiier,'  or  in  a 
mcdullated  nerve. 

will  caiLse  an  extrapolar  current   in  the  cathodic  area,  the  catelectro- 
tonic  current. 

This  polarisation  will  not  disappear  at  once  on  breaking  the 
polarising  current.  The  nerve  or  nei^-model  will  still  be  positively 
polarised  at  the  anode  and  negatively  polarised  at  the  cathode.  On 
connecting  therefore  these  two  points  with  the  galvanometer,  we  shall 
get  a  ciu-rent  in  the  opposite  direction  to  the  previous  polarising 
current,  viz.  from  anode  to  cathode  (Fig.  129).     This  is  the  .so-called 


^■0*^  _^    //  Neqative  polarisation. 
Fig.  129.     Diagram  to  show  direction  of  the  negative  polarisation  current. 

negative  polarisation  of  nerve.  Similarly  in  the  extrapolar  regions  of 
the  nerve  we  shall  have  currents  in  the  same  direction  as  the  previous 
polarising  current,  as  shown  by  the  arrows.  So  far  then  the  nerve 
behaves  exactly  Uke  the  mechanical  model.  If,  however,  we  pass  a  very 
strong  current  through  a  nerve,  and  then  quickly  switch  the  nerve  on  to 
a  galvanometer,  we  find  a  momentary  current  through  the  galvano- 
meter in  the  same  direction  as  the  previous  polarising  ciu-rent.  This 
is  known  as  positive  polarisation  of  nerve.  It  is  absolutely  dependent 
on  the  living  condition  of  the  nerve,  and  is  in  fact  an  excitatory  pheno- 
menon  due  to  the  strong  excitation  which  occurs  at  break  of  the 


318  PHYSIOLOGY 

current  at  the  anode.  Thus  in  the  diagram  (Fig.  130)  a  strong  current 
is  passing  through  the  nerve  from  a  to  k.  When  this  current  is  broken, 
excitation  occurs,  as  we  have  already  learnt,  at  the  anode,  and  this 
excitatory  state  may,  if  the  previous  currents  were  strong,  last  two  or 
three  seconds.  An  excited  tissue  is,  however,  always  negative  towards 
adjacent  unexcited  tissue,  and  therefore  if  we  connect  a  to  k,  there 

£r^     Polarising 


\V2  '      'j 
^-./Ty-"^^   Positive  polarisation 


Fig.  130.      Diagram  to  show  direction  of  the  positive  polarisation  current, 
due  to  a  break  excitation  at  the  anode. 

must  be  a  current  outside  the  nerve  from  k  to  a,  and  in  the  nerve 
from  a  to  k,  viz.  in  the  same  direction  as  the  polarising  crarent.  We 
see  therefore  that  negative  polarisation  is  due  to  polarisation  occurring 
between  an  electrolytic  sheath  and  a  conducting  core,  whereas  positive 
polarisation  is  hardly  a  polarisation  effect  at  all,  but  is  a  current  of 
action. 

PARADOXICAL  CONTRACTION.  If  the  sciatic  nerve  of  a  frog 
be  dissected  out,  and  one  of  the  two  branches  into  which  it  divides  be 
cut,  and  the  central  end  of  this  branch  stimulated,  the  muscles  supplied 


Fig.  131.     Diagram  of  arrangement  for  sho^ving  paradoxical  contraction. 

by  the  other  half  of  the  nerve  contract  to  each  stimulus.  Ligature 
or  crushing  of  the  nerve  x  between  the  points  stimulated  and  the 
point  which  joins  the  main  trunk  puts  a  stop  to  this  effect,  showing 
that  it  is  not  due  to  a  mere  spread  of  current.  The  fibres  passing  down 
n  are  in  fact  stimulated  by  the  electrotonic  current  developed  in 
X  during  the  passage  of  the  exciting  current. 


SECTION  IX 

THE  NATURE  OF  THE  EXCITATORY  PROCESS 

Under  this  heading  we  have  really  two  questions  to  discuss,  namely, 
(a)  the  nature  of  the  change  excited  at  the  stimulated  spot  in  an  excit- 
able tissue,  and  (6)  the  propagation  of  the  excitatory  change  away  from 
the  excited  spot,  e.g.  down  a  nerve  fibre.  That  these  two  phenomena 
are  more  or  less  independent  and  may  be  dealt  with  separately  is 
shown  by  the  result  of  passing  a  constant  current  through  a  parallel- 
fibred  muscle,  such  as  the  sartorius.  In  this  case,  as  we  have  seen 
(p.  214),  at  make  of  the  cmrrent  an  excitatory  change  occurs  at  the 
cathode  and  is  transmitted  throughout  the  whole  length  of  the  muscle, 
giving  rise  to  a  twitch  of  the  muscle.  During  the  passage  of  the 
current  there  is  still  an  excitatory  change  at  the  cathode,  but  limited 
to  a  region  within  one  or  two  milhmetres  of  the  cathode. 

An  attempt  has  been  made  by  Boruttau  and  other  physiologists  to 
explain  the  nerve  process,  not  as  a  wave  of  electrical  change  affecting 
the  substance  of  the  axis  cylinder  itself,  but  as  a  propagated  catelectro- 
tonic  current.  This  observer  found  that,  by  working  with  a  '  platinum 
core  model'  {' Kernleiter ')  (Fig.  126)  of  considerable  length,  the 
catelectrotonic  current  was  developed  at  one  end  of  the  model  some 
appreciable  time  after  a  current  had  been  sent  in  at  the  other  end,  thus 
resembling  a  current  of  action.  It  is,  however,  impossible  to  explain  all 
the  electrical  phenomena  of  nerve  as  due  simply  to  polarisation.  We 
might  go  so  far  as  to  assume  that  the  excitatory  effect  at  the  cathode 
is  due  to  negative  polarisation,  and  that  excitation  at  break,  i.e.  at 
the  anode,  is  caused  by  the  sudden  coming  into  existence  of  a  negative 
polarisation  current ;  but  then  it  would  be  difficult  to  understand 
how  the  excitation,  so  produced  at  the  anode,  should  give  rise  to  a 
current  so  much  exceeding  the  current  which  produced  it  that  it 
would  appear  in  oiu:  external  circuit  as  a  current  of  positive  polarisa- 
tion. 

The  same  objection  would  hold  to  the  comparison  of  a  nerve-fibre 
with  a  submarine  cable.  An  electric  disturbance  produced  at  any 
part  of  a  cable  {i.e.  a  conducting  wire  in  an  insulating  sheath)  is  propa- 
gated along  the  cable  at  a  certain  finite  velocity  which  can  be  calcu- 
lated when  we  know  the  conductivity  of  the  core,  the  capacity  of  tbe 
cable,  and  the  di-electric  constant  of  the  sheatb.     In  all  these  cases 

319 


320  PHYSIOLOGY 

there  must  be  a  decrement  of  the  change  as  it  is  transmitted  away 
from  its  seat  of  origin,  a  decrement  for  the  existence  of  which  there 
is  no  evidence  in  a  nerve  fibre  or  other  excitable  tissue.*  Moreover  the 
phenomenon  of  propagation  of  an  excitatory  process  is  equally  well 
marked  in  tissues,  such  as  muscle  and  non-medullated  nerve  fibres, 
which  show  very  little  of  the  electrotonic  effects  described  in  the  last 
section.  The  absence  of  decrement  in  the  excitatory  process  has  been 
taken  as  an  indication  that  the  axis  cylinder  of  the  nerve  is  the  seat 
of  energy  changes  which  may  be  let  loose  under  the  influence  of  chemical 
or  electrical  changes,  just  as  the  energy  of  a  contracting  muscle  is  set 
free  by  the  exertion  of  an  infinitesimal  force  applied  as  a  stimulus. 
The  nerve  on  this  view  does  not  simply  transmit  the  energy  which  is 
imparted  to  it,  like  a  telegraph  wire,  but  itself  furnishes  the  energy 
of  the  descending  nerve -process. 

Against  this  view  might  be  urged  the  absence  of  phenomena  of 
fatigue  in  nerve,  as  showing  that  nervous  activity  is  not  accompanied 
by  any  expenditure  of  energy  or  using  up  of  material.  But  it  must  be 
remembered  that  this  absence  of  fatigue  holds  aood  only  for  medullated 
nerve  fibres  and  is  not  found  in  non-medullated  nerves,  and  even  in 
medullated  nerves  the  persistence  of  irritability  is  dependent  on  the 
continual  supply  of  a  certain  small  amount  of  oxygen.  It  may  there- 
fore possibly  be  explained  by  a  continual  process  of  restitution  taking 
place  at  the  expense  of  the  sheath.  Fatigue  is  absent,  not  because 
nothing  is  used  up,  but  because  the  assimilative  changes  exactly 
balance  and  make  good  the  dissimilation  involved  in  the  propagation 
of  a  nervous  impulse. 

There  is  thus  a  certain  amount  of  justification  in  the  comparison 
of  a  nerve  fibre  to  a  chain  of  gunpowder,  though  in  the  nerve  fibre  the 
impetus  to  disintegration,  imparted  from  each  particle  to  the  next  in 
order,  consists,  not  in  a  rise  of  temperature  at  the  point  of  ignition,  but 
in  all  probability  in  an  electrical  change  ;  and  the  total  evolution  of 
energy  is  so  small  that  it  cannot  be  measured  as  heat  by  the  most 
sensitive  methods  at  our  disposal.  The  excited  condition  at  any 
segment  of  a  nerve  is  associated  with  a  development  of  electromotive 
forces  at  the  junction  of  the  segment  with  the  adjacent  resting  seg- 
ments. The  current  of  action  thereby  produced  can  pass  by  the 
sheath  of  the  nerve,  so  that  it  must  enter  the  axon  at  the  excited  spot, 
and  leave  it  at  the  adjacent  unexcited  segment.  Hermann  has  sug- 
gested that  in  this  way  the  current  of  action  at  any  excited  spot  may 
excite  the  adjacent  segments  or  molecules,  causing  them  to  become 
negative  and  thus  setting  up  a  current  of  action  which  in  its  turn 
excites  the  molecules  in  order.     In  this  way  the  excitatory  process 

*  It  might  be  urged,  on  the  other  hand,  that  one  would  not  expect  to  find  any 
appreciable  decrement  in  a  cabh;  only  1  to  3  inches  long. 


THE  NATURE  OF  THE  EXCITATORY  PROCESS      321 

may  travel  the  whole  length  of  the  nerve.  Propagation  would  thus 
involve  the  successive  setting  up  of  an  excitatory  process  all  along 
the  nerve  or  excitable  tissue,  though  it  is  difficult  to  see  why  on  this 
theory  every  excitatory  state  should  not  give  rise  to  a  propagated 
change. 

We  are  as  yet  a  long  way  from  a  comprehension  of  the  changes 
involved  in  the  process  of  excitation,  though  we  are  able  to  form  some 
idea  of  many  of  the  factors  which  must  be  involved.  Any  theory 
of  the  excitatory  process  must  take  into  account  the  following 
phenomena  : 

(1)  The  excitatory  state  is  attended  with  an  electrical  change  of 
such  a  nature  that  the  excited  spot  is  negative  to  adjacent  unexcited 
spots.  This  electrical  change  rises  rapidly  to  a  maximum  and  dies 
away  more  slowly,  the  rate  of  its  rise,  and  still  more  of  its  subsidence, 
varying  largely  according  to  the  nature  of  the  tissue  under  investiga- 
tion. 

(2)  The  excitatory  change  is  aroused  only  at  the  poles  of  a  current 
passing  through  the  tissue,  i.e.  at  those  places  where  polarisation  can 
occur  in  consequence  of  the  electrical  movement  of  ions. 

(3)  Excitation  only  occurs  at  the  kathode  at  make  of  the  current, 
and  only  occurs  if  the  current  attains  a  sufficient  strength  within 
a  certain  period  of  time,  the  relation  of  strength  of  current  to  rate  of 
change  varyinii  in  different  tissues. 

(4)  All  living  tissues  are  made  up  of  colloids,  divided  into  com- 
partments by  membranes  of  various  permeabilities  and  permeated 
with  salts  and  other  electrolytes  in  solution. 

Disregarding  for  the  moment  all  considerations  of  structure,  it  is 
possible  to  form  a  hypothesis  of  the  nature  of  electrical  excitation 
which  takes  into  account  the  facts  just  mentioned  and  enables  us  to 
give  a  quantitative  or  mathematical  expression  to  the  factors  involved. 
An  electrical  current  passing  through  a  tissue  containing  membranes, 
impermeable  to  the  dissolved  ions,  will  set  up  differences  of  concentra- 
tions at  and  near  the  membranes.  Xernst,  on  the  supposition  that 
these  differences  of  concentrations,  when  sufficiently  large,  would 
cause  an  excitation,  arrived  at  a  formula  connecting  the  lowest  current 
required  to  excite  with  its  duration,  and  another  formula  connecting 
the  lowest  amplitude  of  an  electrical  current  with  its  frequency. 
The  mathematical  investigation  of  the  question  has  been  continued 
by  A.  V.  Hill  in  conjunction  with  Keith  Lucas.  For  this  purpose 
we  may  suppose  that  the  excitable  unit  is  represented  by  a  cylindrical 
space  closed  at  its  two  ends  by  the  membranes  a  and  B  (Fig.  132)  and 
filled  with  a  solution  of  electrolytes.  If  a  current  be  jia.s^d  from 
B  to  A  the  positively  charged  ions  will  move  towards  a  andUend  to 
accumulate  there.     The  accumulation  of  the  ions  near  the  mt^b^nes 


322  PHYSIOLOGY 

will  be  limited  by  the  tendency  of  the  ions  to  equalise  their  concentra- 
tion in  all  parts  of  the  cell  by  diffusion.  If  we  suppose  that  a  neces- 
sary condition  for  excitation  is  that  the  concentration  of  the  ions  in  the 
neighbourhood  of  one  of  the  membranes  shall  reach  a  certain  definite 
value,  it  becomes  possible  to  calculate  under  what  conditions  of 
strength,  duration,  &c.,  an  electrical  current  will  just  produce  excita- 
tion. The  rise  of  the  excitatory  state  would  here  be  determined  by 
the  rate  at  which  the  ions  accumulate,  the  subsidence  of  the  excitatory 


Fig.  132. 


state  by  the  rate  of  dispersal  of  the  ions  by  diffusion, 
arrived  at  bv  these  observers  has  this  form  : 


The  formula 


i=- 


X 


i-/xe* 
where 

i  is  the  smallest  current  which  will  excite, 

t  is  duration  of  the  current, 
while  \,  fi,  6  are  constants  which  depend  on  : 

(1)  The  distance  between  the  membranes. 

(2)  The  distance  from  the  membrane  at  which  the  concentration 

changes  are  being  considered. 

(3)  The  diffusion  constant  of  the  ion. 

(4)  The  number  of  ions  by  which  a  given  quantity  of  electricity 

is  carried. 

(5)  A  constant  expressing  in  general  terms  the  ease  with  which 

a  propagated  disturbance  is  set  up. 
Investigation  on  these  lines  may  give  us  in  future  sufficient  in- 
formation to  form  a  material  conception  of  the  factors  involved  in 
excitation,  factors  which  in  the  above  formula  have  only  a  symbolic 
existence.  Thus  a  determination  of  the  distance  between  the  mem- 
branes would  give  us  some  clue  to  the  size  of  the  ultimate  excitatory 
units  in  the  tissue  involved.*    The  constant  f/.  has  reference  only  to  the 

*  It  would  be  premature  at  present  to  give  any  histological  significance  to 
Hill  and  Lucas's  diagrammatic  cylinder.  As  Hardy  has  pointed  out,  the  nerve 
cannot  consist  of  a  row  of  such  cylinders,  otherwise  excitation  would  occur 
throughout  the  whole  intrapolaf  region,  and  not  be  confined  to  the  cathode  at 
make  and  the  anode  at  break.  It  may  be  that  we  are  dealing  here  again  with 
the  polarisable  sheath  of  the  '  Kernleiter,'  and  that  the  membrane  A  corresponds 
to  the  siyface  ot  the  axis  cylinder  or  of  its  neuro-fibrils. 


THE  NATURE  OF  THE  EXCITATORY  PROCESS       323 

position  relative  to  the  membranes  at  which  the  changes  of  concentra- 
tion are  effective.  From  Lucas's  experiments  it  would  seem  that  the 
changes  of  concentration  occur  in  the  immediate  neighbourhood  of 
one  of  the  membranes.  Macdonald  has  brought  forward  evidence 
that  the  passage  of  a  current  through  a  nerve  involves  the  setting  free 
of  certain  inorganic  ions.  The  subsidence  of  the  excitatory  state 
depends  on  the  rate  of  diffusion  of  ions.  If,  however,  we  compare  the 
rates  of  subsidence  of  the  excitatory  state  in  different  tissues  we  find 
much  gi-eater  divergence  than  would  be  possible  on  the  assumption 
that  the  diffusion  is  one  affecting  inorganic  ions.  Thus  between  the 
substance  /3  (the  intermediate  substance)  of  the  frog's  sartorius  and 
the  ventricular  muscle  fibre  of  the  same  animal,  the  rate  of  subsidence 
of  the  excitatory  state  changes  in  the  ratio  4000  :  1.  If  the  ions 
concerned  were  simple  ions,  such  as  H',  Ca*,  Na",  CT,  &c.,  it  would  be 
impossible  to  account  for  this  wide  variation,  since  their  velocities  differ 
in  the  ratio  of  10  :  1  at  most.  Moreover  the  effect  of  rise  of  temperature 
on  the  rate  of  subsidence  is  greater  than  the  effect  of  a  similar  rise  on 
ionic  velocities.  It  is  evident  therefore  that  the  theory  is  one  for  use 
as  a  working  hypothesis  only.  That  excitation  is  associated  with 
accumulation  of  ions  in  the  region  of  the  exciting  electrode,  that  the 
subsidence  of  the  excitatory  state  is  due  to  disappearance  by  diffusion 
or  otherwise  of  these  ions,  there  can  be  little  doubt.  But  the  questions 
as  to  the  nature  of  these  ions,  and  their  relation  to  the  colloidal  con- 
stituents of  the  excitatory  tissue,  or  to  other  possible  substances, 
changes  in  which  may  form  an  integral  part  in  the  excitatory  state, 
must  be  left  for  future  investigation. 


CHAPTER  VII 
THE  CENTRAL  NERVOUS  SYSTEM 

SECTION  I 

THE  EVOLUTION  AND  SIGNIFICANCE  OF  THE 
NERVOUS  SYSTEM 

Every  vital  phenomenon  may  be  regarded  as  a  reaction  con- 
ditioned by  some  change  in  the  environment  of  the  animal  and 
adapted  to  its  preservation.  In  the  community  of  cells  forming 
the  whole  organism,  the  defence  of  any  one  part  must  involve  the 
co-operation  of  the  whole  community  ;  no  change  in  a  cell  of  the 
body  can  be  regarded  as  a  matter  of  indifference  to  any  of  the  other 
cells.  For  this  subordination  of  the  activities  of  each  part  to  the  welfare 
of  the  whole,  as  for  the  co-operation  of  all  parts  in  maintaining  the 
welfare  of  each,  a  means  of  communication  is  necessary  between  the 
various  cells.  For  some  of  the  lower  functions  the  channel  of  com- 
munication is  the  blood,  which  serves  as  a  medium  for  carrying 
food  material  from  one  part  of  the  body  to  another,  or  for  the 
transmission  of  chemical  messengers,  which,  elaborated  by  one  set 
of  cells,  may  affect  the  metabolism  of  cells  in  distant  parts  of  the 
body.  This  method  of  correlating  different  activities  would, 
however,  be  too  slow  and  clumsy  for  the  quick  adaptation  of  the 
organism  to  sudden  changes  of  environment.  Such  a  rapid  correlation 
can  be  effected  only  by  a  propagation  of  some  molecular  change  from 
the  seat  of  incidence  of  the  stimulus  either  to  all  parts  of  the  body,  or 
to  some  mechanism  controlling  all  parts  of  the  body.  The  medium 
for  the  propagation  of  a  state  of  excitation  is  furnished  by  the  nervous 
system.  We  have  seen  that  stimuli  of  various  kinds,  involving  such 
various  forces  as  thermal,  mechanical,  chemical,  and  electrical  energy, 
are  transformed  by  a  muscle  or  nerve  fibre  into  what  we  call  a  state 
of  excitation,  which  is  propagated  along  the  fibres,  whether  nerve  or 
muscle,  at  a  certain  definite  rate,  its  passage  in  the  case  of  the  muscle 
being  followed  by  a  wave  of  contraction. 

In  unicellular  animals,  such  as  the  amoeba  and  vorticella,  there 
is   no  differentiation   of  any  structure   which  can   be  regarded   as 

324 


EVOLUTION  OF  THE  NERVOUS  SYSTEM 


325 


peculiarly  nervous.  A  stimulus  applied  to  any  part  of  the  amcEba 
may  evoke  responsive  activity  in  all  other  parts.  A  slight  touch 
applied  to  any  point  on  a  vorticella  will  cause  an  excitation  which  is 
rapidly  propagated  to  the  stalk,  causing  this  to  contract  and  so 
withdraw  the  organism  from  any  possible  injury.  In  the  lowest 
metazoa,  such  as  the  sponges,  we  find  no  special  nervous  structures. 
The  cells  forming  the  sponge  may  react  to  changes  in  their 
environment  by  contraction  or  by  alteration  of  their  relative 
positions.  Many  of  the  cells  can  move  from  one  part  of  the 
sponge  to  the  other  in  response  to  chemical  changes  occurring 
in  the  body  of  the  sponge.  So  far,  however,  no  cells  have  been 
distinguished  as  endowed  above  their  fellows  with  the  property  of 


B 


m.p. 


m.c. 


Fig.  133.     Diagrammatic  representation  of  evolution  of  a  nervous  system. 
(Modified  from  Foster.) 
ec,  epithelial  cell ;  mp,    muscular   process  ;  sc,  sensory  cell ;   np,  nerve 
process  or  fibre  ;  mc,  muscle-cell ;  sup,  sensory  nerve  process  ;  mnf,  motor 
nerve  process  ;  cc,  central  cell. 

irritability  or  the  power  of  reaction  to  stimulus.  It  is  in  the  next 
class,  that  of  the  Coelenterata,  where  we  first  find  a  definite  nervous 
system.  The  object  of  a  nervous  system  is  to  ensure  the  co-operation 
of  the  whole  organism  in  any  reaction  to  changes  in  its  surroundings. 
At  its  first  appearance  therefore  we  should  expect  a  nervous 
system  to  be  developed  in  connection  with  that  layer  of  the  animal 
which  is  in  immediate  relation  to  the  environment,  namely,  the 
epiblast  or  external  layer.  In  some  species  of  hydra,  though  no  typical 
nervous  tissues  have  been  detected,  many  of  the  epithelial  cells  lying 
on  the  surface  are  prolonged  at  their  inner  ends  into  a  long  contractile 
process  (Fig.  133,  a),  so  that  stimuli  applied  to  the  surface  and  acting 
on  the  epithelial  cells  can  cause,  as  an  immediate  response,  a  con- 
traction of  the  underlying  muscular  processes.  We  may  easily 
conceive  that  in  such  an  animal,  among  the  cells  forming  the  epiblast, 
certain  cells  might  become  endowed  with  a  special  sensitiveness  to 
external  changes,  other  cells  being  developed,  like  those  of  the  hydra 


326 


PHYSIOLOGY 


just  mentioned,  into  special  contractile  structures.  If  in  the  course 
of  development  the  protoplasmic  continuity  between  these  two 
sets  of  cells  had  not  become  interrupted  (and  we  have  no  ground 
for  assuming  that  such  an  interruption  occurs  under  normal  circum- 
stances), it  is  evident  that  we  should  have  so  produced  the  simplest 
form  of  a  reflex  arc  (Fig.  133,  b),  namely,  a  sensory  cell,  which  is  stimu- 
lated by  shght  physical  changes  in  its  surroundings  and  is  thereby 
thrown  into  a  state  of  activity  similar  to  that  which  we  have  already 
studied  in  muscle  and  nerve.     This  state  of  activity  would  be  propa- 


R-- 


Fig.  134.     Diagrammatic  view  of  a  jelly-fish.      (Hertwig.) 
u,  umbrella  ;  M,  manubrium  ;  T,,  t.^,  tentacles  ;   V,  velum  ;  K,    nerve 
ring  ;  R,  '  marginal  body.' 

gated  by  the  protoplasmic  channels  to  the  muscular  cell  and  arouse 
there  the  specific  function  of  the  muscle,  namely,  contraction.  In  such 
a  simple  reactive  tissue,  Hues  of  less  resistance  would  be  rapidly  laid 
down  through  the  protoplasmic  continuum,  and  these  hues,  acquiring 
a  specific  structure  or  composition,  would  form  a  network  uniting 
sensory  and  muscular  cells.  Thus  a  stimulus  applied  to  any  sensory 
cell  would  spread  to  the  adjacent  sensory  and  muscular  cells,  and 
the  response  of  the  muscle-cells  would  be  greatest  near  the  stimu- 
lated spot,  gradually  dying  away  as  the  area  of  the  excitation  widened. 
A  further  step  in  the  development  of  such  a  hypothetical  elementary 
nervous  system  would  occur  when  certain  of  the  sensory  cells 
(Fig.  133,  c)  developed  a  special  sensitiveness,  not  to  mechanical 
changes  in  the  environment,  but  to  the  protoplasmic  excitatory 
process   arriving  at   them    along  the    nerve   network.      These   cells 


EVOLUTION  OF  THE  NERVOUS  SYSTEM 


327 


would  act  as  relays  of  force,  picking  up  the  excitations  arriving 
from  the  undifferentiated  sensory  cells,  and  sending  them  on  with 
increased  vigour  along  the  nerve  network.  In  such  a  manner  a  stimulus 
applied  at  one  point  could  be  sent  on  in  successive  relays  from  cell  to 
cell  throughout  the  whole  reactive  tissue  on  the  surface  of  the  body. 
We  cannot  point  to  any  particular  animal  as  presenting  instances 
of  either  of  the  two  types  of  elementary  nervous  system  just  described. 
If  such  exist,  they  have  not  yet  been  investigated,  or  the  undifferen- 
tiated character  of  their  nervous  tissues  has  thwarted  the  efforts  of 
zoologists  to  display  their  specific  characters  by  staining  reagents. 
In  the  lowest  definite  nervous  system  with  which  we  are  acquainted, 
namely,  that  of  the  jelly-fish,  all  three  types  of  cell,  the  sensory  cell, 
the  reactive  or  central  cell,  and  the  motor  cell,  are  already  developed 
and   have   undergone   among  themselves   a   considerable   degree   of 


Fig.  135.  Diagram  of  subepithelial  plexus  of  nerve  fibres  and  nerve-cells,  com- 
municating on  the  one  side  with  the  sensory  epithelium,  and  on  the  other  side 
with  the  subumbrellar  sheet  of  muscle  fibres.     (After  Bethe.) 

differentiation.  In  a  jelly-fish  or  medusa,  such  as  aurelia  or  sarsia 
(Fig.  134),  the  reactive  tissue  of  the  body  is  confined  to  the  under- 
surface  of  the  so-called  umbrella  with  the  tentacles  and  manubrium. 
A  section  through  the  umbrella  shows  a  layer  of  epithelium  con- 
taining differentiated  sense-cells,  below  which  is  a  plexus  or  rather 
network  of  fine  nerve  fibres  with  a  certain  number  of  nerve-cells 
at  the  nodes  of  the  network.  From  this  network  fibres  pass  more 
deeply  to  end  in  a  finer  network  situated  among  a  layer  of  muscle 
fibres  formed,  like  the  sensory  cells,  by  a  difierentiation  of  the  primitive 
epithelium  or  epiblast  (Fig.  135).  Besides  this  diffuse  nervous  system, 
there  is  a  continuous  ring  of  nerve  fibres  round  the  margin  of  the 
umbrella,  thickened  at  intervals  by  the  accumulation  of  nerve-cells, 
which  are  in  close  relation  to  special  collections  of  sensory  cells  in  the 
'  marginal  bodies.'  These  sensory  cells  present  a  differentiation 
among  themselves,  some  being  apparently  determined  for  the  reception 
of  mechanical  stimuli,  others  for  the  reception  of  light  stimuli,  while 
others  again  are  found  in  close  relation  with  little  masses  of  calcium 
carbonate  crystals,  by  the  direction  of  the  weight  of  which  the  cells 
are  able  to  react  to  changes  in  the  position  of  the  animal  in  space. 


328 


PHYSIOLOGY 


In  the  jelly-fisli  therefore  the  nervous  or  reactive  system  has  aheady 
acquired  a  considerable  degree  of  differentiation. 

We  may  study  the  behaviour  of  a  more  primitive  system  if  we 
remove  the  special  sense-organs  of  the  medusa  by  cutting  off  the 
whole  of  the  marginal  ring  with  its  contained  marginal  bodies 
(Fig.  136).  We  have  then  a  layer  of  contractile  tissue,  innervated 
by  a  nerve  network,  and  covered  by  a  layer  of  epithelium  containing 
sense-cells.  To  this  network  is  attached  the  manubrium,  which 
represents  the  mouth  and  stomach  of  the  animal.     In  such  a  mutilated 


Fig.  136.  Figure  of  a  jelly-fish  in  which  all  the  marginal  bodies  except 
one  have  been  removed,  and  Avhich  has  been  incised  in  various  directions 
so  as  to  divide  the  nerve  ring  and  all  the  '  long  paths,'  so  that  only 
the  diffuse  nerve  network  remains  functional.     (Romanes.) 

jelly-fish  it  is  easy  to  show  that  a  stimulus  applied  to  one  spot  on  the 
surface  travels  outwards  from  the  excited  spot  to  all  parts  of  the 
bell.  The  stimulus  is  propagated  also  to  the  manubrium,  which  in 
some  species  bends  in  the  direction  of  the  excited  spot — ^that  is  to 
say,  in  the  direction  which  represents  the  shortest  possible  path 
from  the  excited  spot  to  the  manubrium.  This  preparation  rarely 
presents  any  automatic  activity.  It  may  react  to  a  constant  stimulus 
by  a  rhythmic  series  of  contractions,  but  remains  perfectly  motion- 
less in  the  absence  of  stimulus.  The  unmutilated  jelly-fish  presents 
rhythmic  contractions  of  its  sub-umbrella  tissue  which  are  inaugurated 
in  any  or  all  of  the  marginal  bodies  and  serve  to  drive  the  animal 
onwards  through  the  water  in  which  it  is  immersed.  The  rhythmic 
contractions  may  be  initiated,  augmented,  or  diminished,  in  response 
to  stimuli  of  light,  mechanical  irritation,  or  changes  in  the  position 


EVOLUTION  OF  THE  NERVOUS  SYSTEM 


320 


of  the  whole  animal  acting  on  the  marginal  bodies.  In  the  reaction 
of  an  animal  to  external  stimuli  it  must  be  an  advantage  if  the 
energies  of  the  whole  can  be  concentrated  in  defence  of  any  one  part 
and  be  evoked  by  a  stimulus  applied  at  one  point.  Such  a  co-opera- 
tion of  the  whole  for  the  benefit  of  the  part  involves  the  existence 
of  direct  paths  from  the  stimulated  point  to  all  parts  of  the  animal 
if  the  reaction  is  to  take  place  with  any  promptitude.  In  the  medusa 
we  find  a  beginning  of  such  '  long  paths.'  The  general  direction 
of  the  fibres  of  the  network  is  radial,  and  there  is  a  concentration 
of  such  fibres  in  the  neighbourhood  of  the  marginal  bodies,  so  that 
an  excitation  can  pass  more  readily  from  a  sense-organ  to  the  manu- 
brium than  it  can  laterally  along  the  circumference  of  the  animal. 


Fig.  137.     Schema  showing  the  utility  of  the  multiplication  of  neurons  and 
their  grouping  in  central  ganglia.     (Caj-U..) 

A,  an  ideal  invertebrate  with  only  cutaneous  '  sensory  '  neurons. 

B,  invertebrate,  such  as  a  medusa,  with  sensory  and  motor  neurons, 
but  no  central  nervous  system. 

c,  invertebrate  (e.g.  Annelid)  in  which  the  motor  neurons  are  concen- 
trated in  central  ganglia. 

a,  sensory  neuron  ;  b,  muscle  ;  c,  motor  neuron. 

Moreover,  a  stimulus  which  is  too  slight  to  excite  a  reflex  contraction 
of  the  muscular  tissue  may  travel  along  the  nerve  tissue  to  each  of 
the  marginal  gangha  and  arouse  these  to  a  discharge  of  motor  impulses. 
We  have  therefore  in  the  medusa  sensory  cells  of  different  sensibilities  ; 
central  cells  specially  adapted  to  reacting  to  and  reinforcing  a  nerve 
stimulus  started  by  a  small  change  in  the  environment  ;  a  general 
nerve  network  propagating  the  excitatory  changes  in  all  directions, 
but  with  special  ease  in  certain  directions  ;  and  a  reactive  muscular 
tissue  which  carries  out  movements  at  the  end  of  the  chain  of  excita- 
tion, all  the  elements  forming  the  chain  being  derived  from  epiblastic 
cells. 

A  further  differentiation  of  a  nervous  system,  such  as  that  just 
described,  must  in  the  first  place  involve  the  laying  down  of  more 
'  long  paths  '  and  the  collection  of  the  special '  central '  cells  into  closely 
connected  masses  (gangha),  so  as  to  concentrate  the  control  of  the 
reactions  of  the  body,  and  to  permit  of  the  ready  subordination  of 
every  part  to  the  needs  of  the  whole.     A  special  direction  is  given  to 


330 


PHYSIOLOGY 


this  development  by  the  evolution  of  animals,  such  as  the  worms 
and  crustaceans,  which  are  segmented  and  capable  of  locomotion. 
The  fact  that  these  animals  are  segmented  determines  the  collection 
of  the  central  cells  into  a  chain  of  ganglia, 
one  ganglion  or  pair  of  ganglia  being  provided 
for  each  segment.  In  the  act  of  locomotion 
it  is  of  advantage  to  the  animal  that  those 
sense-organs  or  sensory  cells  which  are  iwo- 
jicient,  i.e.  which  are  stimulated  by  changes 
in  the  environment  originating  at  a  distance 
from  the  animal,  should  be  collected  together 
near  that  part  which  goes  first,  namely,  the 
head  end.  Thus  the  projected  sensations  of 
sight,  those  which  are  excited  by  chemical 
changes  in  the  surrounding  medium  and  repre- 
sent the  sense  of  smell,  and  those  which  are 
specially  aroused  by  vibrations  in  the  surround- 
ing medium  and  correspond  to  those  which 
we  call  the  sense  of  sound,  are  in  the  majority 
of  these  animals  subserved  by  organs  situated 
near  the  head  end. 

The  wisdom  of  a  man  is  measured  by  his 
foresight.  The  chances  of  an  animal  in  the 
struggle  for  existence  are  determined  by  the 
degree  to  which  the  reactions  of  the  animal 
to  its  immediate  environment  are  held  in  check 
in  response  to  stimuli  arising  from  approaching 
events.  An  animal  without  power  to  see, 
smell,  or  hear  its  enemy  will  receive  no 
impulse  to  fly  until  it  is  already  within  its 
enemy's  jaws.  It  must  therefore  be  of  ad- 
vantage to  a  segmented  animal  that  the 
activities  of  the  whole  chain  of  segmented 
ganglia  should  be  subservient  to  those  central 
nerve-cells  which  are  in  direct  connection 
with  the  projicient  sense-organs  at  the  head. 
The  influence  exerted  by  the  head  ganglia  will 
be  in  the  first  place  inhibitory  of  the  direct 
reaction  excited  in  each  segment  by  stimulation 
of  its  surface,  and,  for  this  influence  to  be  propagated,  long  tracks  must 
be  laid  down,  joining  up  ganglion  to  ganglion  and  propagating  impulses 
from  the  head  ganglia  to  the  most  distant  part  of  the  chain.  As  a 
type  of  such  a  system  we  may  refer  to  the  crayfish.  In  this  animal 
the  central  nervous  system  consists  of  a  chain  of  thirteen  ganglia, 


Fig.  138.  View  of  central 
nervous  system  of  cray- 
fish.     (After  Ytjng  and 

VOGT.) 

a,  cerebral  ganglion. 

b,  commissure. 

e,  suboesophageal ganglion. 

g,  first  abdominal  ganglion. 

/,  oesophagus. 

m,  optic  nerve. 

p,  antennary  nerve. 

s,  stomato-gastric  nerve. 


EVOLUTION  OF  THE  NERVOUS  SYSTEM  331 

namely,  six  abdominal  ganglia,  six  thoracic  ganglia,  and  one  supra- 
cesophageal  or  cerebral  ganglion.  In  the  abdomen  and  thorax  the 
ganglia  form  a  longitudinal  series  situated  in  the  middle  line  of  the 
ventral  aspect  of  the  body  close  to  the  integument.  All  give  origin 
to  a  variable  number  of  nerves,  which  are  distributed  partly  to  the 
muscles,  partly  to  the  skin  and  sense-organs.  They  are  connected 
by  longitudinal  bands  of  nerve  fibres  or  commissures,  which  are  double, 
each  ganglion  being  bilobed.  The  most  anterior  of  the  thoracic 
ganglia,  which  is  the  largest,  is  marked  at  the  side  by  notches,  as  if  it 
were  made  up  of  several  pairs  of  ganglia  fused  together.  From  this 
ganglion  two  commissures  pass  forward  round  the  gullet  to  unite  in 
front  of  this,  tube,  just  behind  the  eyes,  with  the  transversely  elon- 
gated mass  of  ganglion  cells  and  fibres  called  the  supraoesophageal 
ganglion.  This  ganglion  consists  of  three  fused  pairs  of  ganglia, 
which  have  been  termed  the  protocerehron,  the  deuterocerehron,  and 
the  tritocerebron.  The  most  anterior  gives  origin  to  the  optic  nerves, 
which  run  by  the  optic  stalks  to  the  eyes.  From  the  middle  ganglion 
on  each  side  a  tegumentary  nerve  passes  to  ramify  in  the  integument 
and  from  the  inferior  surface  the  antennulary  nerves  pass  to  the 
internal  antennae.  From  these  small  branches  are  distributed  to 
the  organ  of  hearing.  The  posterior  protuberance  of  the  brain  gives 
origin  to  the  antennary  nerves  which  pass  to  the  large  external 
antennae  of  the  animal.  The  first  thoracic,  or  suboesophageal,  ganglion 
gives  origin  to  ten  pairs  of  nerves  which  are  distributed  to  the  man- 
dibles, to  the  jaws  or  maxillae,  to  the  maxillipedes,  and  to  the  branchial 
appendages  of  the  latter. 

When  we  investigate  the  structural  basis  of  such  a  nervous  system 
we  find  that,  as  in  medusa,  the  starting-point  of  the  reflex  arc  is 
in  certain  neuro-ej)ithelial  cells  (Fig.  139)  lying  on  the  surface 
of  the  body.  These  cells  are  spindle-shaped,  and  have  one  short 
process  passing  to  the  surface,  and  a  long  process  which  runs  in  a 
nerve  fibre  or  collection  of  fibres  towards  the  ganglion  of  the  segment. 
Arrived  at  the  ganglion  it  divides  into  two  branches,  which  pass 
towards  the  two  ends  of  the  body  and  become  lost  in  the  granular 
material  forming  the  inner  part  of  each  ganglion.  The  ganglia 
themselves  consist  internally  of  this  ininctated  substance  or  granular 
material,  and  externally  of  a  capsule  of  ganglion-cells.  Each  of 
the  ganglion-cells  sends  one  thick  process  towards  the  centre,  which 
rapidly  divides,  some  of  the  branches  passing  into  the  granular 
material,  while  one  branch  passes  outwards  in  a  nerve  to  end  in  a 
network  of  fine  fibrils  within  the  muscles  on  the  surface  of  the  body. 
The  nervous  impulse  excited  in  the  sensory  cell  on  the  periphery 
travels  therefore  up  a  nerve  fibre  into  the  granular  substance  of  the 
ganglion.     From  this  granular  substance  it  is  collected  by  the  fine 


332 


PHYSIOLOGY 


branches  of  the  ganglion-cells  and  is  transmitted  by  them  along  the 
motor  nerve  fibre  to  the  muscles.  Opinions  were  long  divided  as 
to  the  nature  of  the  central  granular  material.  It  consists  entirely 
of  a  close  felt -work  of  fibres,  which  may  be  regarded  as  processes 
either  of  the  sensory  nerve  fibres  or  of  the  nerve-cells.  The  typical 
reflex  arc  in  this  case  therefore  is  formed  by  two  nerve -cells  with  their 
processes.  Such  a  nerve-cell  with  its  processes  is  spoken  of  as  a 
neuron.     The  first  neuron,  the  recipient  neuron,  or  receptor,  is  repre- 


FiG.  139.     Diagram  of  nervous  system  of  a  segmented  invertebrate  (earth- 
worm or  crayfish).     (From  Schafer,  after  Retzitjs.) 
s',  sensory  cells  ;  5,  afferent  nerve-fibres  ;  7n,  motor  neuron  ;  *',  central 
or  intermediate  cell. 

sented  by  the  sensory  cell  with  its  two  processes  in  the  granular 
material.  The  second  neuron  is  formed  by  the  ganglion-cell  with  its 
finely  branched  dendritic  processes  in  the  granular  matter  and  its 
motor  axon,  which  passes  into  the  muscle  fibres.  As  to  the  manner 
in  which  the  impulse  passes  from  the  branches  of  one  cell  into  those 
of  the  other,  opinions  are  still  divided.  The  question  will  have  to 
be  more  fully  considered  when  we  come  to  deal  with  the  vertebrate 
nervous  system.  Many  believe  that  there  is  no  anatomical  continuity 
between  the  two  neurons,  and  that  the  excitatory  change  is  transmitted 
by  a  mere  contiguity,  a  change  in  one  set  of  nerve-endings  exciting  a 
corresponding  change  in  another  set  of  nerve-endings  in  immediate 
contact  with  them.  By  certain  methods,  however,  it  is  possible  to  show 


EVOLUTION"  OF  THE  NERVOUS  SYSTEM 


333 


the  existence  of  an  anatomical  continuum  throughout  the  whole  nervous 
system  in  these  invertebrate  animals.  Apathy  and  Bethe  have  demon- 
strated the  presence  of  a  continuous  system  of  neurofibrils,  much 
smaller  than  an  indi\'idual  nerve  fibre,  which,  starting  in  a  sensory 
cell,  pass  into  a  network  of  filjrils  forming  the  greater  part  of  the  central 
granular  matter.  From  this  network  neurofibrils  run  along  the 
dendrites  into  the  ganglion-cells,  forming  there  a  small  network  through 
the  centre  of  which  a  neurofibril  is  continued  down  the  nerve  processes 
again,  and  jaasses  out  along  the  motor  nerve  to  end  in  a  network  of 
fibrils  among  the  muscle  fibres.     In  a  system  so  constituted  it   is 


Ner^eCclL. 


.^xfensor    n. 


Fig.  140. 
system. 


NerveCdl 


Diagram  of  a  reflex  arc  in  a  (neuro-fibrillar)  invertebrate  nervous 
(Bethe.)     The  efferent  paths  are  coloured  red,  the  afferent  black. 


evident  that,  although  an  excitatory  process  passing  along  a  given 
fibril  may  find  certain  paths  easier  than  others,  and  so  maintain  a 
constant  prescribed  path  through  the  nerve  system,  yet  it  will  be  pos- 
sible, by  sufficiently  increasing  the  strength  of  the  excitatory  process, 
to  cause  it  to  travel  in  all  directions  in  the  central  nervous  system  and 
to  evoke  in  this  way  a  general  activity  of  all  parts  of  the  body,  a  condi- 
tion in  fact  found  to  obtain  in  the  normal  animal.  It  is  significant 
that,  although  a  great  number  of  fibrils  pass  into  the  bodies  of  the 
ganglion-cells,  yet  in  many  cases,  especially  in  crustaceans,  fibrils  are 
to  be  foinid  sweeping  from  the  tieuropilem  or  nerve  network  of  the 
granular  substance  into  a  nerve  process,  and  thence  into  its  motor 
axon  without  any  time  entering  the  body  of  the  cell  (Fig.  1-iO). 


SECTION  II 

THE  NERVOUS  SYSTEM  OF  VERTEBRATES 

In  these,  as  in  the  invertebrata,  the  central  nervous  system  is 
developed  by  an  involution  of  the  epiblast,  revealing  thereby  its 
primitive  relations  to  the  surface  of  the  body.  At  an  early  period 
in  foetal  life,  shortly  after  the  formation  of  the  two  layers  of  epiblast 
and    hypoblast,    a   thickening   is    observed    in   the    epiblast.      This 


mc 
my 


Fig.  141.     Transverse  section  of  human  embryo  of  2'4  mm.  to  show  developing 

neural  canal.     (T.  H.  Bryce.) 

nc,    neural    canal ;    mc,    muscleplate ;    iny,  outer    wall  of   somite ; 

8C,  sclerotome. 

thickening  soon  gives  place  to  a  groove,  the  neura]  groove  (Fig.  141), 
and  the  walls  of  the  groove  folding  over  form  a  canal,  the  neural  canal, 
which  is  dilated  at  the  head  end  of  the  embryo  to  form  three  enlarge- 
ments known  as  the  cerebral  vesicles. 

When  first  formed  the  canal  is  oval  in  cross-section,  its  wall  being 
made  up  of  a  layer  of  columnar  cells  between  the  outer  extremities 
of  which  are  seen  smaller  rounded  cells.  The  internal  layer  of 
columnar  cells  send  a  process  peripherally  which  branches  at  the  end 
so  as  to  form  a  close  mesh  work  of  fibres.  These  fibres  branch  more 
and  more  as  development  progresses,  and  eventually  form  the  support- 
ing tissue  of  the  adult  central  nervous  tissue,  known  as  the  neuroglia. 
As  the  wall  of  the  canal  grows  in  thickness,  some  of  the  cells  may 
wander  outwards  and  form  neuroglia-cells  with  numerous  radiating 
branches.     In  the  adult  nervous  system  little  is  left  of  these  cells 

334 


THE  NERVOUS  SYSTEM  OF  VERTEBRATES 


335 


except  their  nuclei,  so  that  the  neuroglia  appears  as  a  close  felt-work 
of  fibres,  to  which  here  and  there  nuclei  are  attached.  These  cells  are 
formed  from  the  most  superficial  layer  of  the  invaginated  epiblast, 
and  are  spoken  of  as  spongioblasts.  The  deeper  layer  of  cells,  which 
are  to  give  rise  to  the  permanent  nerve-cells,  and  are  therefore  known 
as  neuroblasts,  rapidly  divide  and  form  a  thick  layer  surrounding  the 
internal  layer  of  spongioblasts,  through  which  pass  the  peripheral 
processes  of  the  latter.  When  first  formed  these  cells  have  no  processes. 
Later  on  each  neuroblast  acquires  a  pear  shape,  the  stalk  of  the  pear 
ha\ang  a  somewhat  bulbous  ex- 
tremity (Fig.  142).  The  stalk  con- 
tinually elongates,  and  the  elongated 
process  may  leave  the  spinal  cord 
altogether  and  grow  outwards  to 
any  part  of  the  body  of  the  embryo, 
or  may  pass  to  other  parts  of  the 
central  nervous  system.  This  long 
process  of  the  developing  nerve- 
cell  is  known  as  the  axon.  Some 
time  after  its  formation  other  pro- 
cesses grow  out  from  the  cell,  which 
soon  branch  and  end  in  the  im- 
mediate neighbourhood  of  the  cell. 
The  axons  of  the  cells  near  the 
ventral    part    of  the   neural    tube 

grow  out  to  the  different  muscles  of  Fig.  142.  Neuroblasts  from  the  spinal 
1       1      T  1  ^1  11  cord  of  a  chick  embryo.  (Cajal.) 

the  body,  where  they  end  m  close 

connection  with  the  muscular  fibres 

by  an  arborisation  which  forms  the 

end-plate.     They  provide  an  efferent 

path  for  impulses  running  from  the  central  nervous  system  to  the 

musculature  of  the  body.     The  afferent  channel  is  formed  in  a  some- 

Avhat  different  manner.     Even  before  the  neural  groove  has  closed  in, 

a  thickening   of   the  epiblast  is  seen  immediately  external  to  the 

groove  on  each  side.     This  thickening  becomes  divided  into  a  series 

of  collections  of  cells   lying    immediately  under  the  epiblast  on  the 

lateral  and  dorsal  surface  of  the  neural  canal.     The  cells,  which  are 

at  first  round  or  oval,  send  off  two  processes  in  opposite  directions  so 

that  they  become  bi-polar  (Fig.  143).     One  process  passes  into  the 

central  nervous  system,  where  it  divides,  some  of  its  branches  being 

distributed  in  the  nervous  system  at  the  same   level,  while  others 

run  a  considerable  distance  towards  the   head  immediately  outside 

the   tube   of    nerve-cells.      The   other    process    grows    downwards. 

along    with    the    processes    from   the    ventral    cells    of    the    tubo. 


,  three  neuroblasts  stained  to  show 
neuro-fibrils  ;  a,  a  bi-polar  cell. 

,  a  neui'oblast  showing  the  '  incre- 
mental cone  '  c. 


336 


PHYSIOLOGY 


towards  the  periphery  of  the  body,  where  it  ends  in  close  connection 
with  the  surface  in  the  various  sense-organs  of  the  skin  and  muscles. 
These  collections  of  bi-polar  cells  form  the  posterior  root  ganglia. 
In  fishes  they  retain  their  primitive  character  throughout  life,  but  in 
mammals  the  bi-polar  cell  is  to  be  found  only  in  the  spiral  and  vesti- 
bular ganglia  which  give  origin  to  the  fibres  of  the  eighth  nerve.    In  all 


Fig.  143.  Section  through  developing  .spinal  cord  and  nerve-roots  from 
chick  embryo  of  fifth  day.  (Cajal.) 
A,  ventral'root ;  b,  dorsal  root ;  c,  motor  nerve- cells  ;  D,  sympathetic 
ganglion-cells  ;  E,  spinal  ganglion-cells  still  bi-polar  ;  r,  mixed  nerve  ; 
b,  c,  d,  motor  nerve  fibres  to  /,  developing  spinal  muscles  ;  e,  a  sensory 
nerve-trunk. 

the  other  ganglia  the  shape  of  the  cell  becomes  modified  by  an  approxi- 
mation of  the  points  of  attachment  of  the  two  processes  until  finally 
the  cell  becomes  uni-polar,  giving  off  one  process  which  divides  by  a 
T-shaped  junction  into  two,  one  of  which  runs  towards  the  spinal  cord, 
while  the  other  takes  a  peripheral  course  as  the  afferent  nerve  fibre.  The 
central  nervous  system  thus  becomes  provided  with  a  '  way  in  '  and  a 
'  way  out  '  for  the  chain  of  impulses  concerned  in  a  nervous  reaction 
or  reflex  action.  The  further  development  of  the  spinal  cord  is 
mainly  determined  by  the  extension  of  the  axons  of  the  cells  outside 
the  tube  of    cells  themselves,  and  by  the  provision  of  the  '  long 


THE  NERVOUS  SYSTEM  OF  VERTEBRATES  337 

paths  '  which  are  a  necessary  condition  of  increased  efficiency  of 
the  reacting  organ.  Some  time  after  the  out|^o\vi:h  of  the  axon  a 
medullary  sheath  is  formed,  apparently  by  the  agency  of  the  axon 
itself,  so  that  each  group  of  axons  leaving  or  entering  the  cord  forms 
a  bundle  of  medullatcd  nerve  fibres.  The  long  branches  of  the 
posterior  or  dorsal  roots  running  up  towards  the  head  form  a  mass  of 
fibres  behind  the  tube  of  cells  known  as  the  posterior  columns.  Fibres 
starting  in  the  spinal  cord  itself  run  upwards  and  downwards  to  end 
in  other  parts  of  the  cord,  or  in  the  more  anterior  divisions  of  the 
central  nervous  system  forming  the  brain,  and  surround  the  neural 
tube  on  its  ventral  and  lateral  aspects  with  a  sheath  of  white 
matter.  To  these  white  fibres  are  added  others,  which  take  origin 
in  the  brain  and  pass  all  the  way  down  the  cord.  Meanwhile  the 
cells  themselves  become  separated  by  the  ramifications  between 
them  of  the  branches  of  axons  entering  the  cord,  as  well  as  of 
the  dendrites  of  the  cells  themselves.  Thus,  ni  its  adult  form, 
the  spinal  cord  consists  of  a  central  mass  of  nerve-cells  and  fibres, 
known  as  the  grey  matter,  which  is  encased  in  a  sheath  of  white 
matter  formed  of  medullated  nerve  fibres.  The  cord  itself  is  cylin- 
drical in  shape,  and  is  divided  into  two  symmetrical  halves  by  the 
anterior  and  posterior  fissures.  In  each  half  of  the  cord  the  grey 
matter  on  cross-section  is  crescentic  in  shape,  presenting  an  anterior 
or  ventral  horn  and  a  posterior  or  dorsal  horn,  and  is  connected 
with  the  corresponding  mass  in  the  other  half  of  the  cord  by  grey 
matter  known  as  the  anterior  and  posterior  grey  commissures.  Between 
the  two  grey  commissures  is  the  central  canal,  relatively  very  minute 
when  compared  with  the  condition  in  the  foetus  and  lined  by  a  single 
layer  of  columnar  ciliated  epithelium,  the  cells  of  which  are  directly 
descended  from  the  neural  epithelium  lining  the  medullary  canal. 

THE  STRUCTURE  OF  NERVE-CELLS 
In  the  adult  animal  a  typical  nerve-cell,  such  as  those  forming  a 
prominent  feature  in  the  anterior  horn  of  the  spinal  cord,  is  a  large 
cell  with  many  branches.  It  has  a  large  vesicular  nucleus  with  very 
little  chromatin,  which  may  be  collected  into  one  or  two  nucleoli. 
The  body  of  the  cell  presents  different  appearances  according  to  the 
manner  in  which  it  has  been  treated  for  histological  examination. 
When  separated  from  the  surrounding  tissues  by  means  of  dissociating 
fluids  it  may  present  traces  of  striation,  the  individual  .stria3  running 
from  one  process  to  another  of  the  cell.  When  treated  fresh  with 
methylene  blue,  or  hardened  by  alcohol  or  corrosive  sublimate  and 
stained  with  methylene  blue  or  toluidine  blue,  the  protoplasm  is 
seen  to  contain  angular  masses  which  are  deeply  coloured  with  the 
dye  (Fig.  144).    These  masses  are  known  as  the  Nissl  granules  or 


338 


PHY^SIOLOGY 


bodies.  By  other  methods  it  is  possible  to  demonstrate  that  the 
whole  protoplasm  of  ^e  cell  between  the  Nissl  bodies  is  pervaded 
by  fine  fibrils,  which  enter  the  cell  from  the  processes  and  may  run 
out  of  the  cell  by  the  axon  or  may  run  into  some  of  the  other  shorter 
processes  (Fig.  147).  The  processes  of  the  cell,  as  is  evident  from  their 
development,  are  of  two  kinds.  The  axon  which  becomes  continuous 
with  the  axis  cylinder  of  the  medullated  nerve  fibre  arises  from  a  part 
of  the  cell  body  known  as  the  axon  hillock,  which  is  the  only  part 
of  the  cell  free  from  Nissl  bodies  (Fig.  145).  The  other  processes,  which 
may  be  very  numerous,  are  known  as  the  dendrites.    They  are  generally 


Fig.    144.      Nerve-cell   from   the   spinal    cord, 
stained  by  Nissl's  method. 
a,  axis-cylinder  process  or  axon  ;  b,  proto- 
plasm  of   cell,  consisting   of  c,  fibriJlated 
ground  substance,  and  e,  the  granules  of 
Nissl ;   d,  nucleus.     (LENHOSsfeK.) 


Fig.  145.  The  point  of  origin 
of  the  axon,  the  '  nerve- 
hillock,'  highly  magnified, 
to  show  absence  of  Nissl's 
granules  from  the  origin  of 
the  process.     (Held.) 


thicker  than  the  axon  at  their  origin  from  the  cell,  but  rapidly  diminish 
in  size  as  they  give  off  branches,  the  branches  apparently  terminating 
freely  in  the  grey  matter  in  the  immediate  neighbourhood  of  the  cell. 
In  specimens  stained  by  the  Golgi  method  the  dendrites  may  some- 
times present  a  somewhat  serrated  outline.  The  Nissl  bodies  of  the 
cell  extend  some  way  into  the  dendrites. 

A  nerve-cell  with  all  its  processes,  axon,  and  dendrites  is  spoken 
of  as  a  neuron.  From  the  development  of  the  central  nervous  system 
in  vertebrates,  it  is  evident  that  the  nervous  path  of  every  reaction 
must  be  made  up  of  two  or  more  neurons.  If  we  take,  for  example, 
the  simplest  possible  reaction  which  might  be  effected  through  a 
single  segment  of  the  spinal  cord,  we  see  that  the  afferent  impulse 
might  be  started  by  some  stimulus  applied  to  the  ramifications  in 
the  skin  of  the  distal  processes  of    the  posterior  root  ganglion-cell 


THE  NERVOUS  SYSTEM  OF  VERTEBRATES  339 

(c/.  Fig.  133).  The  nerve  impulse  so  started  is  carried  by  the  nerve 
fibre  past  the  T-shaped  junction  in  the  posterior  root  ganglion  into 
the  cord,  and  along  a  branch  of  the  entering  nerve  fibre  which  runs 
ri»ht  across  the  cord  to  terminate  in  the  neighbourhood  of  the  anterior 
horn-cells.  Here  the  impulse  must  be  transmitted  in  some  way 
to  the  dendrites  or  body  of  one  of  the  large  motor  nerve-cells  in  the 
anterior  horn,  whence  it  is  carried  along  the  axon  of  the  cell,  leaving 
the  cord  by  the  anterior  root  and  passing  down  a  peripheral  nerve 
to  the    end-plate  on    a    muscle  fibre.     Here  again  by  some  means 


Figs.  146  and  147.     Nerve-cells  from  spinal  cord.     (Bethe.) 

Fig.   14(),  showing  Ciolgi  network,   and  neurolibrils :  il,  e.  f,  junctions  of 
.    axons  with  Colgi  network.     Fig.  147,  showing  neurofibrils  and  Nissl  bodies. 

the  arrival  of  the  impulse  excites  the  muscle  to  contract.  This 
reaction  never  takes  place  in  the  contrary  sense,  i.e.  no  impulse 
started  in  the  motor  nerve  can  travel  back  through  the  spinal  cord 
and  along  the  sensory  nerve.  Although  an  impulse  excited  in 
the  nerve  passes  easily  to  the  muscle,  an  excitatory  process 
started  in  the  muscle  itself  is  confined  to  this  tissue  and  never 
extends  to  the  nerve  fibre.  Apparently  the  same  rule  holds 
good  within  the  grey  matter  of  the  central  nervous  system, 
where  two  neurons  come  into  relation  with  one  another.  An 
impulse  passes  easily  from  the  axon  of  one  into  the  dendrites 
and  cell  of  the  other  neuron,  but,  so  far  as  we  are  aware,  it  is  impossible 
by  exciting  an  axon  to  cause  a  retrograde  wave  of  excitation 
to  pass  through  its  corresponding  cell  and  into  the  terminations 
of  the  axons  in  immediate  contact  with  the  cell.     This  statement 


340  PHYSIOLOGY 

is  sometimes  laid  down  under  the  name  of  the  '  Law  of  Forward 
Direction.'  It  might  be  also  spoken  of  as  the  irreciprocal  conduction 
of  the  nerve  arc.  The  character  of  a  reaction  to  any  stimulus,  applied 
to  the  surface  of  the  body,  is  determined  by  the  course  which  the 
impulse,  excited  in  the  afferent  nerves,  takes  on  entrance  into  the 
central  nervous  system.  This  course  is  laid  down  by  the  connections 
of  the  neurons  through  which  the  nerve  impulse  passes.  In  the 
central  nervous  system  therefore,  more  than  in  any  other  part  of 
the  body,  function  is  directly  dependent  on  structure.  Theoretically 
if  we  had  a  perfect  knowledge  of  the  connections  of  the  neurons  in 
the  central  nervous  system  and  knew  the  nerve  fibres  afiected  by 
any  given  stimulus,  we  should  be  able  to  prophesy  exactly  the  result 
of  such  stimulus.  In  the  case  of  the  simpler  reactions  this  is  already 
possible,  but  in  the  higher  parts  of  the  nervous  system  the  enormous 
complexity  of  the  systems  of  neurons  excludes  any  possibility  of 
our  forming  more  than  a  general  idea  as  to  the  nerve  paths  traversed 
in  any  given  reaction  ;  and  the  variations  which  exist  from 
individual  to  individual  must  always  prevent  in  the  intact  animal 
an  absolute  prediction  of  the  results  of  any  stimulus. 


SECTION   ITT 

GENERAL  CHARACTERISTICS  OF  REFLEX 
ACTIONS 

There  are  certain  features  common  to  all  reactions,  carried  out 
through  the  intervention  of  the  central  nervous  system,  which  must 
be  regarded  as  determined  by  the  properties  of  the  neurons,  i.e.  the 
conducting  links  in  the  chain  of  excitatory  tissues  intervening 
between  the  stimulated  spot  on  the  exterior  and  the  reacting  tissue, 
muscle  or  gland.  These  characteristics  may  be  roughly  classified 
as  follows  : 

(1)  LOCALISATION,  In  a  simple  system  of  neurons  a  given 
stimulus  will  nearly  always  produce  the  same  reaction.  In  a  frog 
possessing  only  a  spinal  cord,  the  upper  parts  of  the  central  nervous 
system  having  been  destroyed,  any  harmful  stimulus  applied  to  a  toe 
will  cause  a  lifting  of  the  leg.  If  the  motor  nerve  to  the  gastroc- 
nemius be  excited,  the  whole  muscle  contracts.  If  one  of  the  nerve- 
roots  entering  into  the  formation  of  the  sciatic  nerve  be  excited,  only 
certain  fibres  of  the  gastrocnemius  contract,  the  locality  of  the  reacting 
fibres  being  determined  by  their  connection  with  the  excited  nerve 
fibres.  In  the  same  way  the  contraction  of  certain  muscles  of  the 
leg,  in  response  to  a  stimulus  applied  to  the  skin  of  the  foot,  is  deter- 
mined by  the  fact  that  the  nerve  fibres,  which  carry  the  impulses  from 
the  toe  into  the  spinal  cord,  divide  there  and  make  connections  with 
the  motor  neurons,  whose  axons  are  distributed  to  the  several  muscles 
involved  in  the  reaction.  The  connection  of  the  sensory  with  the  motor 
neuron  may  be  direct,  but  in  most  cases  the  impulse  has  to  pass  through 
intermediate  neurons  before  arriving  at  the  motor  neurons.  The  path 
of  the  impulse,  however,  in  spite  of  its  enormous  extension,  is  as  definite 
as  is  the  path  from  an  excited  motor  nerve-root  to  a  muscle  fibre. 

(2)  DELAY.  Instead  of  one  nerve-ending  intervening  between 
the  stimulated  nerve  and  the  reacting  tissue,  there  will  be,  in  the 
case  of  the  reflex  action,  two,  three,  or  more  nerve-endings  interpolated 
in  the  path  of  the  impulse.  These  nerve-endings  are  the  fields  of  con- 
junction, the  sijna'pses,  between  the  axon  of  one  neuron  and  the  den- 
drites and  cell  body  of  the  neuron  next  in  the  chain. 

We  have  seen  that  there  is  a  distinct  difference  between  the  latent 

341 


342  PHYSIOLOGY 

period  of  a  muscle  excited  through  its  nerve  as  compared  with  the 
latent  period  when  excited  directly,  and  we  ascribed  this  latent  period 
to  a  delay  in  the  motor  end-plate.  We  should  expect  therefore  to  find 
that  the  delay  or  latent  period  in  the  case  of  a  reflex  action,  i.e.  the 
lost  time  in  the  conversion  of  an  afferent  into  an  efferent  impulse 
in  the  central  nervous  system,  would  be  appreciable  and  would 
increase  with  the  complexity  of  the  response — that  is,  with  the  number 
of  neurons  involved  in  the  reaction.     Such  is  indeed  the  case. 

In  determining  the  actual  '  lost  time '  in  the  central  nervous 
system  for  any  given  reflex,  it  is  necessary  to  subtract  from  the  total 
delay,  interposed  between  the  application  of  the  stimulus  and  the 
resultant  movement,  the  time  taken  by  the  impulse  in  travelling  to 
and  from  the  central  nervous  system,  as  well  as  the  latent  period 
of  tiie  muscles  themselves.  The  remainder  is  known  as  the  '  reduced 
reflex  time.'  Wundt  found  in  the  frog,  when  a  reflex  contraction  of 
the  gastrocnemius  was  excited  by  a  stimulation  of  a  posterior  root 
of  the  same  side,  that  the  reduced  reflex  time  was  -008  sec. 
For  a  crossed  reflex  the  delay  was  increased  by  -004  sec.  If 
we  assume  that  one  additional  neuron  is  involved  in  the  crossed 
reflex,  the  lost  time  at  a  synapse  would  be  -004  sec.  ;  if  two  cells 
are  intercalated,  the  synapse  delay  Vould  be  only  -002  sec.  Since 
the  uncrossed  reflex  has  a  delay  of  -008  sec,  at  least  two,  and 
possibly  four,  synapses  are  involved  in  the  path  of  this  simple  reflex. 

The  blinking  excited  by  stimulation  of  the  eyelid  has  a  reduced 
reflex  time  of  -047  sec. 

(.3)  SUMMATION.  When  contractile  tissues,  such  as  striated  or 
unstriated  muscle,  are  excited  by  single  shocks,  a  certain  minimal 
strength  of  stimulus  is  necessary  in  order  to  produce  a  contraction. 
Weaker  stimuli  are  spoken  of  as  sub-minimal,  and  when  applied  singly 
have  apparently  no  effect  on  the  muscle.  In  deahng  with  the 
properties  of  involuntary  muscle  we  saw  that  a  sub-minimal  stimulus 
is  not  necessarily  devoid  of  effect  because  it  fails  to  evoke  a  contrac- 
tion, since,  if  repeated  at  sufficiently  frequent  intervals,  a  summation 
of  stimulus  occurs,  so  that  at  the  fifth  or  sixth  application  a  stimulus, 
which  was  previously  ineffective,  becomes  effective  and  a  contraction 
results.  The  muscle  will  now  continue  to  respond  to  each  stimulus, 
but,  if  the  excitations  be  discontinued  for  a  time,  reapplication  of  a 
stimulus  of  the  same  strength  becomes  once  more  ineffective.  This 
summation  of  stimulus  is  a  prominent  feature  in  all  reflex  actions,  so 
much  so  that  it  may  be  often  impossible  to  evoke  a  reaction  to  a  very 
strong  single  induction  shock,  whereas  the  application  of  a  tetanising 
current  too  weak  to  be  felt  on  the  tongue  may  produce  a  marked 
reaction.  We  shall  have  occasion  later  on  to  deal  with  special  examples 
of  this  summation  of  stimulus. 


CHARACTERISTICS  OF  REFLEX  ACTIONS  343 

(4)  FATIGUE.  Ill  tlic  iiiuscle-nerve  preparation  the  weakest 
point  and  tluit  wliiuli  soonest  suli'ers  from  fatigue  is  the  end-plate,  or 
rather  the  fieki  of  conjunction  of  nerve  fibre  and  muscle  fibre.  In 
the  central  nervous  system  the  synapses  of  the  different  neurons  are 
equally  susceptible,  and  since  several  of  such  synapses  are  involved 
in  every  reflex  action,  we  should  expect  to  find  that  the  central  nervous 
system  would  show  signs  of  fatigue  before  the  peripheral  structures. 
If  a  given  reaction  be  repeatedly  elicited  by  applying  a  stimulus  to  a 
certain  area  of  the  surface,  the  reaction  becomes  feebler  and  finally 
disappears  altogether  long  before  any  signs  of  fatigue  in  the  motor 
apparatus  can  be  detected  by  stimulation  of  the  motor  nerve  itself. 
This  fatigue  is  produced  equally  well  if  the  reaction  be  excited  by 
stimulating  a  sensory  nerve  directly,  and  since  we  know  that  it  is 
practically  impossible  to  fatigue  nerve  fibres,  we  must  conclude  that 
the  seat  of  fatigue  is  in  the  grey  matter  of  the  spinal  cord  itself. 

(5)  '  BLOCK  '  OR  RESISTANCE.  In  the  central  nervous  system 
there  is  an  absolute  block  to  the  passage  of  an  impulse  backwards 
through  a  synapse,  i.e.  from  a  nerve-cell  or  its  dendrites  into  the  end 
ramifications  of  an  axon.  The  phenomena  of  fatigue  show  that 
there  is  a  certain  degxee  of  resistance  at  the  synapse  to  the  passage  of 
an  impulse  in  the  normal  direction,  and  that  this  resistance  is  rapidly 
increased  under  the  conditions  which  produce  fatigue.  When  we 
study  the  structure  of  the  central  nervous  system  more  fully,  we  find 
that  although  there  are  certain  shortest  possible  paths,  i.e.  ones 
involving  few  neurons,  for  every  impulse  arriving  at  the  central 
nervous  system,  yet  so  extensive  is  the  branching  of  the  entering 
nerve  fibres  and  so  complex  are  the  neuron  systems  with  which  they 
come  in  connection  that  an  impulse  entering  along  one  given  fibre  could 
spread  to  practically  every  neuron  in  the  spinal  cord  and  brain.  Such 
a  result  is  indeed  observed  in  animals  poisoned  by  strychnine.  In 
such  animals  the  slightest  stimulus  applied  to  any  part  of  the  skin 
'excites  strong  tonic  spasms  in  tlio  whole  musculature  of  the  body. 
Every  single  nerve  fibre,  that  is  to  say,  can  discharge  into  every 
motor  neuron  of  the  cord.  That  this  result  does  not  ensue  on  localised 
stimulation  in  a  normal  animal  is  dependent  on  the  varying  resistance 
to  the  passage  of  an  impulse  into  the  several  neurons  with  which  the 
entrant  fibre  comes  in  relation.  A  small  stimulus  will  discharge 
therefore  only  along  the  few  neurons  where  the  resistance  is  lowest. 
Increase  of  the  stimulus,  either  by  increase  of  its  strengrth  or  by 
summation  of  weak  stimuli,  will  enable  the  impulse  to  spread  along 
more  neurons  and  therefore  will  elicit  a  more  widespread  response. 
Only  when  the  l)locks  are  entirely  removed  by  the  administration  of 
strychnine,  or  when  the  stimuli  are  abnormally  powerful  and  long 
continued,  will  the  impulse  spread  to  all  regions  of  the  central  nervous 


344  PHYSIOLOGY 

system,  so  that  response  becomes  general  and  inco-ordinate  instead 
of  local  and  adapted  to  the  stimulus. 

(6)  FACILITATION  OR  '  BAHNUNG.'  The  passage  of  a  nervous 
impulse  across  a  synapse  or  series  of  synapses  in  the  central  nervous 
system  has  a  twofold  effect.  If  the  passage  be  too  often  repeated 
phenomena  of  fatigue  are  produced,  and  there  is  an  increase  of  the 
block  at  each  synapse.  If,  however,  the  stimulus  be  not  excessive 
and  the  reaction  not  too  frequently  evoked,  the  effect  of  passage  of 
an  impulse  once  is  to  diminish  the  resistance,  so  that  a  second  applica- 
tion of  the  stimulus  evokes  the  reaction  more  easily.  The  process  of 
summation  in  fact  is  chiefly  in  the  direction  of  removal  of  block.  We 
have  a  close  analogy  to  this  process  of  facilitation  in  the  '  staircase 
phenomenon  '  observed  in  cardiac  and  unstriated  muscle.  In  these 
tissues  the  repetition  of  a  sub-minimal  stimulus  renders  it  in  time 
effective,  and  then  repetition  of  the  now  effective  stimulus  causes 
a  gradually  increasing  height  of  contraction,  which  depends  on  the 
state  of  the  contracting  tissue  itself  and  cannot  be  evoked  by  changes 
in  the  strength  of  the  stimulus.  This  process  of  facilitation  or  '  Bah- 
nung  '  is  of  great  interest  in  connection  with  the  development  of  '  long 
paths  '  in  the  central  nervous  system,  and  more  especially  with  the 
acquirement  of  new  reactions  by  the  higher  animals.  The  Law  of 
Facilitation  is  really  the  Law  of  Habit.  When  an  impulse  has  passed 
once  through  a  certain  set  of  neurons  to  the  exclusion  of  others  it  will 
tend,  other  things  being  equal,  to  take  the  same  course  on  a  future 
occasion,  and  each  time  that  it  traverses  this  path  the  resistances  in 
the  path  will  be  smaller.  Education  is  the  laying  down  of  nerve- 
channels  in  the  central  nervous  system,  while  still  plastic,  by  this 
process  of  '  Bahnung '  along  fit  paths,  combined  with  inhibition  (by 
pain)  in  the  other  unfit  paths.  Memory  itself  has  the  process  of 
'  facilitation  '  as  its  neural  basis. 

(7)  INHIBITION.  The  constant  occurrence  of  a  reaction  in  response 
to  a  given  stimulus  is  obtained  only  if  care  be  taken  to  isolate  the  seg- 
ment of  the  central  nervous  system  involved  from  the  entry  of  other 
afferent  stimuh.  As  a  rule,  if  two  stimuli  be  appHed  simultaneously 
at  different  points,  the  reaction  which  ensues  will  not  be  a  combined 
one,  the  resultant  of  the  reactions  which  would  be  normally  condi- 
tioned by  each  single  stimulus,  but  will  be  a  response  to  one  of  the 
stimuU,  which  we  must  therefore  regard  as  the  more  effective.  The 
reaction  to  the  other  stimulus  is  either  abolished  altogether  or  comes  on 
after  a  considerable  period  of  delay.  The  central  nervous  system 
can  apparently  attend  to  only  one  thing  at  a  time.  In  physiological 
terms  we  should  say  that  every  effective  reaction  inhibits  every  other 
reaction.  In  the  spinal  cord  of  the  frog  the  normal  withdrawal  of  the 
foot  in  response  to  stimulation  of  the  toe  of  the  same  side  can   be 


CHARACTERISTICS  OF  REFLEX  ACTIONS  345 

inhibited  by  strong  stimulation  of  the  other  sciatic  nerve,  by  stimulation 
of  the  spinal  cord  at  a  higher  level,  or  by  stinuilation  of  the  optic  lobes. 
Immediately  after  pitfiing  the  brain  of  the  frog,  the  whole  animal 
becomes  flaccid  and  motionless,  and  for  the  next  few  minutes  it  is 
impossible  to  elicit  any  reaction  by  stimulation,  however  strong, 
applied  to  the  skin  of  the  body.  In  the  production  of  this  condition 
of  '  shock,'  the  inhibition  of  all  the  spinal  centres,  produced  by  the 
strong  stimulation  of  the  injury  to  the  brain  and  medulla,  plays 
at  any  rate  an  important  part.  We  may  say  that  the  passage 
of  an  impulse  through  a  chain  of  neurons  diminishes  the  block  for 
subsequent  impulses  at  each  synapse  that  it  traverses,  but  increases 
during  its  passage  the  block  in  all  the  adjacent  synapses. 

In  dealing  with  the  special  reactions  of  the  spinal  cord  we  shall 
have  occasion  to  refer  more  fully  and  in  greater  detail  to  many  of 
these  properties  which  are  characteristic  of  all  reflexes.  Before 
however  treating  of  the  functions  of  the  separate  parts  of  the  central 
nervous  system  in  the  higher  mammals,  it  may  be  of  interest  to  consider 
the  exact  natm-e  of  the  structure  intervening  between  neuron  and 
neuron  at  each  field  of  conjunction  or  synapse,  as  well  as  the  significance 
of  the  two  chief  elements  of  the  central  nervous  system,  nerve-cell  and 
nerve  fibre,  in  the  production  of  co-ordinated  purposive  reactions. 


SECTION  IV 

NATURE  OF  THE  CONNECTION  BETWEEN 
NEURONS 

The  study  of  the  development  of  the  central  nervous  system  in 
higher  animals  has  shown  that  this  system  is  made  up  of  neurons, 
the  connections  of  which  determme  the  possible  paths  of  impulses 
in  the  adult  cord.  The  first  stage  in  the  development  of  the  neuron  is  a 
single  cell  without  processes,  and  it  is  only  by  the  growth  of  these 
processes  out  from  the  cell  that  the  sphial  cord  becomes  capable  of 
serving  as  an  aggregate  of  conducting  paths.  Moreover  the  deferred 
acquisition  of  an  influence  of  one  neuron  on  the  next  neuron  in  the  line 
of  impulse,  or  at  any  rate  on  the  peripheral  tissue  which  receives  the  end 
arborisation  of  its  axon,  is  shown  by  the  fact  that  entire  destruction 
of  the  spinal  cord  in  the  embryo  at  an  early  stage  in  its  development 
does  not  prevent  in  any  way  the  development  of  the  voluntary  muscles 
(Harrison) ;  although,  after  birth,  a  severance  of  the  connection  between 
spinal  cord  and  skeletal  muscle  leads  to  a  rapid  degeneration  and 
atrophy  of  the  latter.  In  the  muscle-nerve  preparation  there  is 
an  apparent  break  of  structure  at  the  termination  of  the  nerve 
in  the  muscle  fibre,  any  continuity  between  nerve-ending  and  con- 
tractile substance  being  subserved  by  undifferentiated  protoplasm. 
There  is  therefore  no  difficulty  in  conceiving  a  propagation  across  a 
similar  nerve-ending  or  synapse,  between  the  axon  of  one  neuron  and 
the  cell  body  or  dendrites  of  another  neuron.  If,  however,  the  con- 
ception we  have  formed  above  of  the  evolution  of  a  nervous  system 
from  a  continuous  conducting  protoplasmic  network,  by  a  process  of 
faciUtation  or  '  Bahnung '  attended  by  histological  differentiation, 
be  correct,  we  should  expect  to  find  in  the  fully  developed  brain 
and  spinal  cord  some  traces  at  any  rate  of  continuity  throughout 
the  whole  system  of  neurons.  The  question  as  to  the  existence  of 
anatomical  continuity  from  neuron  to  neuron  has  been  hotly  dis- 
cussed both  for  vertebrates  and  invertebrates.  In  the  case  of  the 
latter,  evidence  in  favour  of  the  continuity  of  neuro-fibrillsefrom  sensory 
surface  to  reacting  tissue  is  very  strong..  Many  observers,  especially 
Apathy,  Bethe,  and  Held,  have  described  a  similar  continuity  in  the 
nervous  system  of  mammals.     The  last-named  observer  regards  this 

346 


NATURE  OF  CONNECTION"  BETWEEN  NEURONS     347 

continuity  as  a  product  of  later  development  and  as  due  to  a  process  of 
concrescence  occurring  between  the  axon  terminations  and  the  bodies  of 
the  nerve-celLs  with  which  it  comes  in  contact.  It  is  easy  to  show  the 
existence  of  a  fibrillar  structure  both  in  the  nerve-cell  and  in  the  nerve 
fibre  (Fig.  148).  The  axis  cylinder  of  the  nerve  fibre  can  be  regarded 
as  made  up  of  fine  fibrillae  embedded  in  an  interfibriliar  substance. 
At  the  nodes  of  Ranvier  the  interfibriliar  substance  is  interrupted,  the 
fibrillae  alone  extending  into  the  next  internode  and  representing  the 


Fig.  148.  Part  of  an  anterior  cornual 
cell  from  the  calf's  spinal  cord, 
stained  to  show  neurofibrils. 
(Bethe.) 

Ax,  axon  ;  n,  h,  c,  dendrites. 


Fig.  149.  Arborisation  of 
collaterals  from  the  pos- 
terior root-fibres  round 
the  cells  of  the  posterior 
horn.    (Ramon  y  Cajal.) 


continuous  structiu:e  w^iich  determines  the  conducting  power  of  the 
nerve  fibre.  In  the  nerve-cell  the  fibrilloD  occupy  all  the  space  between 
the  Nissl  bodies,  passing  from  dendrite  to  dendrite,  and  many  of  them 
from  all  the  dendrites  and  all  parts  of  the  cell  sweeping  through  the 
axon  hillock  to  form  the  fibrillar  of  the  nerve  fibre.  The  existence  of 
these  fibrillar  structures  in  nerve-cell  and  nerve  fibre  is  accepted  by 
most  histologists.  The  question,  however,  of  the  connection  between 
tiie  fibrilhc  of  one  axon  and  those  of  the  next  neuron,  i.e.  the  hi.stology 
of  the  synapse,  presents  much   greater  difticulties  and    has  excited 


348 


PHYSIOLOGY 


much  difference  of  opinion.  If  we  examine  a  nerve-cell  such  as  a  cell 
of  Purkinje  of  the  cerebellum,  or  a  cell  of  Clarke's  column  in  the  cord, 
we  find  that  it  is  surrounded  by  a  thick  basket-work  of  fibres  which 
are  the  arborisations  or  end  terminations  of  the  axons  which  pass  to 
the  cell  to  enter  into  functional  relationships  with  it  (Figs.  149  and 
150).  This  pericellular  network  is  of  great  extent  and  may  equal  in 
total  diameter  the  diameter  of  the  cell  itself.  Whether  the  basket- 
work  is  really  a  network,  or  merely  a  felt-work  in  which  the  fine 
fibres    intertwine    among    each    other    without    becoming    actually 


Fig.  150.  Basket-work  of  fibre* 
around  two  cells  of  Purkinje. 
(Cajal.) 

a,  axis-cylinder  or  nerve-fibre 
process  of  one  of  the  corpuscles 
of  Purkinje  ;  h,  fibres  prolonged 
over  the  beginning  of  the  axis- 
cylinder  process  ;  c,  branches  of 
the  nerve-fibre  processes  of  cells 
of  the  molecular  layer,  felted 
together  around  the  bodies  of 
the  corpuscles  of  Purkinje. 


Fig.  151.     Superficial^network  of  Golgi  surrounding 
two   cells  from  the    cerebral   cortex  of  the  cat  ; 
Ehrlich's  method.     (Cajal.) 
A,  large   cell ;    B,  small  cell ;     a,  a,  folds   in   the 

network  ;  fc,  a  ring-like  condensation  of  the  network 

at  the  poles  of  the  larger  cell ;  c,  spinous  projections 

from  the  surface. 


continuous  at  any  point,  is  difficult  to  make  out.  On  the  periphery  of 
the  cell  itself  another  network  has  been  described  and  is  known  as 
the  Golgi  network  (Fig.  151).  This  has  been  displayed  both  by 
the  process  of  impregnation  with  silver  chromate  (Golgi  method), 
as  well  as  by  staining  wdth  methylene  blue.  Some  authors  have 
regarded  this  network  as  an  artefact  due  to  precipitation  of  albuminous 
fluids  on  the  surface  of  the  cell.  According  to  Bethe,  however,  the 
Golgi  network  on  the  one  hand  receives  fibres  from  the  encircling  peri- 
cellular basket-work  of  axons,  and  on  the  other  hand  gives  off 
towards  the  interior  of  the  cell  fine  fibrils,  which  are  continuous  with  the 
neuroftbrillae  of  the  cell  and  pass  out  in  its  axon.      The  diagi-ammatic 


NATURE  OF  CONNECTION  BETWEEN  NEURONS      349 

course  of  a  nerve  impulse  according  to  Bethe  is  represented  in  the 
accompanying  diagram  (Fig.  152).  An  impulse  starting  from  the 
periphery  of  the  body  travels  up  the  distal  process  of  the  posterior 
root  ganglion-cell,  passes  either  through  the  cell  or  directly  to  the 
central  proce^ss,  and  travels  along  this  to  the  terminations  of  the 
posterior  root  fibres  round  a  posterior  horn-cell.  Here  it  passes  into 
the  peri-cellular  basket-work  or  a_xon  netvp-ork,  thence  into  the  Golgi 
network  and  along  the  fibrilla)  of  the  cell  out  by  the  fibrilla)  of  the  axon 
and  so  to  a  fresh  spiapse  with  a  cell  of  the  anterior  horn. 

There  are  certain  physiological  difl&culties  in  the  acceptance  of  this 
doctrine  of  continuity  through  the  central  nervous  system.     Even 


Fig.  152.     Schema  of  the  neurofibrillar  continuum,  involved  in  an  ordinary 
reflex  act  in  a  vertebrate  nervous  system.     (Bethe.) 


if  it  be  true,  it  would  not  in  any  way  upset  the  importance  of  the  neuron 
theory.  Every  plant  or  animal  individual  must  be  regarded  as  a  proto- 
plasmic continuiim.  With  growth  of  the  living  matter,  its  metabolic 
functions  demand  the  dispersion  of  nuclear  material  through  the 
protoplasm,  and  this  is  effected  by  division  of  the  nucleus.  Considera- 
tions of  strength  and  rigidity  demand  the  division  of  the  protoplasm 
into  compartments  or  cells,  which,  at  first  at  an}'  rate,  remain  in  proto- 
plasmic continuity.  This  division  has  probably  a  further  advantage 
in  that  lesions  of  parts  of  the  individual  entail  merely  the  death  of  the 
cells  immediately  affected  and  do  not  necessarily  spread  to  the  whole 
organism.  Thus  in  the  central  nervous  system  injury  to  one  axon 
causes  degeneration  of  the  axon  below  the  point  of  section,  but  the 
degeneration  stops  short  at  the  end  arborisation  and  does  not 
spread  into  the  next  neuron.  If  we  assume  that,  in  consequence  of  the 
straitness   of     the    path,   the    propagation    through   the  fibriilee   is 


350  PHYSIOLOGY 

especially  difficult  in  the  synapse,  most  of  the  phenomena  described 
above  as  characteristic  of  the  reactions  which  take  place  in  the  central 
nervous  system  can  be  easily  explained  on  the  theory  of  continuity 
of  the  fibrillfe.  The  serious  difficulty  in  the  acceptance  of  this  theory 
is,  however,  the  '  Law  of  Forward  Direction,'  i.e.  the  fact  that  an 
impulse  will  pass  from  an  axon  to  the  next  neuron,  but  will  not  pass 
backwards  across  the  synapse  from  the  cell  body  to  the  contiguous  axon. 
Bethe  suggests  that  this  rule  of  Forward  Direction,  which  is  possibly 
present  only  in  the  more  highly  developed  nervous  systems,  may  be 
due  to  a  species  of  "  polarity  "  of  the  nerve-fibril,  of  such  a  nature  that 
an  impulse  is  strengthened  and  so  assisted  on  its  passage  in  the 
normal  direction,  but  is  diminished  and  finally  abolished  when  it 
passes  in  the  opposite  direction.  Such  an  explanation  is  unsatis- 
factory, since  there  is  absolutely  no  experimental  evidence  of  the 
existence  of  such  polarity  in  a  nerve  fibre ;  all  the  evidence  that  we 
have  at  present  points  to  a  nerve  fibre  having  the  power  of  propagating 
equally  well  in  either  direction.  It  is  certainly  more  useful  to  regard 
a  synapse  as  of  the  natiu-e  of  a  motor  nerve-ending,  in  which  an  im- 
pulse arriving  along  the  branches  of  an  axon  excites  a  fresh  impulse 
in  the  excitable  tissue,  i.e.  the  nerve-cell,  with  which  the  branches  of 
the  axon  come  in  contact.  Moreover  the  neurons  are  formed  without 
any  structural  connection  with  the  future  destination  of  their  axons. 
These  grow  out  as  processes  with  thickened  amoeboid  extremities. 
Harrison  has  shown  that  the  growth  of  the  axon  from  the  cell  may  be 
observed  under  the  microscope  in  a  neuroblast  separated  altogether 
from  the  body,  and  kept  on  a  warm  stage  in  a  thin  layer  of  coagulated 
lymph.  It  is  possible  that  we  may  have  to  distinguish  two  types 
of  nervous  system,  viz.  : 

(a)  A  neurofibrillar  type,  peculiar  to  invertebrata,  with  conduction 
in  all  directions. 

(6)  A  synaptic  type,  of  later  evolution,  and  forming  the  greater 
part  of  the  nervous  system  of  vertebrata. 


SECTION  V 

FUNCTIONS  OF  THE  NERVE-CELL 

When  a  unicellular  organism,  containing  a  single  nucleus,  is  cut  into 
two  parts,  both  continue  to  live  for  some  time,  each  performing 
active  movements  and  evincing  all  the  phenomena  which  we 
associate  with  activity  and  therefore  with  destructive  katabolism. 
For  the  continued  existence  of  a  cell  the  processes  of  constructive 
metaboHsm,  or  anabolism,  must  take  place  imri  -passu  with  those 
of  disintegxation,  and  for  this  the  presence  of  the  nucleus  is 
necessary.  Hence,  in  a  few  days,  the  half  cell  with  the  nucleus 
has  repaired  its  loss  and  become  once  again  a  normal  individual, 
whereas  the  half  without  a  nucleus  undergoes  degeneration  and 
death.  The  axon  of  a  nerve- cell  can  be  regarded  as  analogous  to  a 
long  pseudopodium  of  an  amoeba.  Like  this,  if  cut  away  from  that 
part  of  the  cell  containing  the  nucleus,  though  capable  for  a  time  of 
discharging  its  active  function  of  propagation  of  excitatory  impulses, 
yet  it  finally  dies,  death  of  the  nerve  fibre  occurring  in  the  mammal 
within  three  to  five  days  after  separation  of  the  axon  from  the  cell. 
Every  nerve-cell  therefore  may  be  looked  upon  as  a  trophic  centre 
of  the  nerve  fibre  proceeding  from  it  as  well  as  of  the  medullary 
sheath,  which  is  practically  a  product  or  secretion  of  the  axis 
cylinder.  But  has  the  nerve-cell  any  more  important  functions  to  dis- 
charge ?  It  has  long  been  customary  to  endow  the  nerve-cell  with  all 
the  properties  which  are  distinctive  of  a  nervous  system,  and  to 
ascribe  to  it  the  active  part  in  the  origination  of  automatic  actions, 
in  the  reflection  of  afferent  impulses,  and  in  the  supply  of  energy  to 
all  nervous  processes.  That  the  passage  of  impulses  through  the  nerve- 
centres  requires  the  expenditure  of  energy  by  these  centres  can  be 
proved  in  various  ways.  In  the  first  place,  we  have  the  fact  that  in 
all  nervous  systems,  at  any  rate  of  the  higher  animals,  arrangements 
are  made  for  their  free  supply  with  oxygen.  Very  short  deprivation 
of  oxygen  causes  a  complete  block  throughout  the  system,  in  many  cases 
preceded  by  a  short  period  of  increased  excitability  or  ease  of  trans- 
mission. If,  in  the  rabbit,  the  thoracic  aorta  be  clamped  for  a  few 
minutes,  the  hind  limbs  become  paralysed,  and  if  the  obstruction  be 
continued  for  half  an  hour,  there  is  widespread  degeneration  and  death 
of  the  cells  with  their  fibres  in  the  grey  matter  of  the  lumbar  and 

351 


352  PHYSIOLOGY 

sacral  cord.  In  the  second  place,  the  ready  production  of  fatigue 
of  the  nervous  system  points  to  a  considerable  using  up  of  material 
as  a  condition  of  the  passage  of  nerve  impulses.  In  many  instances, 
moreover,  an  infinitesimal  stimulus  travelling  up  a  few  nerve  fibres  may 
excite  widespread  activity  of  the  whole  central  nervous  system  with 
the  discharge  of  impulses  along  practically  every  nerve  of  the  body. 
Thus  the  presence  of  a  crumb  on  the  larynx  will  excite  impulses 
travelling  up  the  superior  laryngeal  nerve,  which  in  themselves  can 
involve  but  little  expenditure  of  energy.  The  result,  however,  of  their 
arrival  at  the  central  nervous  system  is  the  discharge  of  impulses  along 
the  motor  nerves  causing  spasmodic  contractions  of  almost  every 
muscle  in  the  body.  It  seems  beyond  doubt  then  that  energy  is  evolved 
in  the  central  nervous  system  as  a  result  of  metabolic  changes,  and 
that  energy  may  be  added  to  impulses  passing  through  the  central 
nervous  system,  which  therefore  acts  as  a  relay  of  force.  But  this 
activity  does  not  necessarily  require  the  presence  or  co-operation  of 
nucleated  cells.  In  dealing  with  the  nature  of  a  nerve  impulse  we  had 
reason  to  conclude  that  there  may  be  an  actual,  though  minimal,  ex- 
penditure of  energy  by  the  axis  cylinder  with  the  passage  of  each  nerve 
impulse.  The  non- nucleated  parts  of  a  cell,  whether  the  axon  or  the  cell 
body,  are  equally  capable  of  this  evolution  of  energy,  and  we  might  con- 
ceive therefore  of  a  nervous  system  which,  existing  for  a  few  days,  might 
act  as  a  normal  reflex  centre  in  the  entire  absence  of  the  nucleated 
cell  bodies.  This  conception  has  been  realised  by  Bethe  in  an  experi- 
ment on  the  crab  (Carcinus  menas).  In  this  animal  the  reflex  move- 
ments of  the  tentacle  are  carried  out  by  a  ganglion  situated  at  its  base. 
As  in  the  other  Crustacea,  the  cell  bodies  in  this  ganglion  lie  outside 
the  mass  of  neuro-fibrils  in  the  centre,  forming  a  sort  of  capsule  (Fig. 
153).  Bethe  was  able,  under  the  dissecting  microscope,  to  remove 
the  cell  bodies  without  interfering  with  the  nerves  entering  or  leaving 
the  central  mass  of  fibrils.  All  the  nerve  processes  with  their  connec- 
tions were  therefore  left  intact.  In  animals,  operated  in  this  way, 
Bethe  found  that  for  two  or  three  days  the  tentacle  reacted  normally 
to  stimuli  applied  to  its  surface.  The  reflex  functions  of  the  ganglion 
were  not  in  any  way  affected  by  the  removal  of  the  nucleated  bodies 
of  the  cells.  A  similar  experiment  would  be  impossible  in  the  central 
nervous  system  of  vertebrates,  since  impulses  must  of  necessity  pass 
through  the  cell  body  on  their  way  from  the  termination  of  one  axon 
to  the  beginning  of  the  next.  In  the  spinal  root  ganglion,  however,  most 
of  the  cells  lie  on  the  surface.  In  the  rabbit  Steinach  exposed  a 
posterior  root  ganglion,  separating  it  from  all  its  vascular  supply,  but 
leaving  its  nervous  attachments  intact.  The  wound  was  opened  every 
day  for  the  next  few  days  and  an  instrument  passed  under  the  ganglion 
so  as  to  divide  any  newly  formii^g  vessels.   As  a  result  of  the  deprivation 


FUNCTIONS  OF  THE  NERVE-CELL 


303 


of  blood-supply  the  ganglion-cells  died.  But  Steinach  found  that  nerve 
impulses  were  still  conducted  perfectly  well  tlii-oii'ih  the  ganglion  at  a 
time  when  microscopic  examination  showed  a  comj>lete  atro))hy  of 
all  cells.  It  is  therefore  only  in  virtue  of  the  fact  that  the  nerve-cell  is 
the  seat  of  the  nucleus,  and  therefore  of  the  assimilative  functions  of 
the  neuron,  that  any  pre-eminent  importance  can  be  ascribed  to  it  in 
the  building  up  of  a  reactive  nervous  system. 

Prominent    among  the  functions  with  which   the  nerve-cell  has 
been  endowed  is  that  of  automaticity  of  actioii  in    the    absence  of 


Fig.  153.  Diagrammatic  representation  of  the  brain  of  Carcinus  to  show 
the  parts  involved  m  Bethe's  expcriinont.  The  dotted  line  x  shows 
the  incision  employed  to  isolate  the  neuropilem  of  the  ganglion  of  the 
second  tentacle. 


stimulus  other  than  that  supplied  by  its  own  metabolism  or  by  the 
fluids  w^iich  bathe  it.  A  'priori  there  is  no  reason  to  deny  to  the  neuron 
a  property  which  is  possessed  by  other  cells  of  the  body,  such  as  the 
muscular  cells  of  the  heart,  and  which  is  a  fundamental  quality  of 
undifferentiated  protoplasm.  The  purpose,  however,  for  which  these 
cells  have  been  evolved  and  differentiated  is  that  of  reaction,  of 
adapting  the  organism  to  changes  in  its  environment,  and  it  is  doubtful 
whether,  in  this  differentiation,  it  has  retained  any  automatic 
properties  whatsoever.  In  the  absence  of  any  afferent  impulse  the 
whole  central  nervous  system  would  probably  be  inert.  In  a  frog 
retaining  only  the  spinal  cord  Hering  divided  all  the  posterior  roots. 
The  frog  remained  flaccid  and  motionless.  Injection  of  strychnine 
was  powerless  to  evoke  the  usual  tetanic  spasms.     In  such  a  strych- 

23 


354  PHYSIOLOGY 

iiinised  frog,  however,  it  was  only  necessary  to  open  the  wound  and 
touch  one  of  the  divided  posterior  roots  to  throw  the  whole  body  into 
convulsions.  As  shown  by  Sherrington  and  Mott,  division  of  all  the 
afferent  nerves  coming  from  the  upper  limb  in  monkey  or  man  entirely 
abolishes  all  contractions  of  the  Hmb,  which  are  usually  effected 
through  the  intermediation  of  the  cerebral  cortex.  Cutting  off  the 
major  portion  of  the  afferent  impulses  to  the  respiratory  centre  does 
not,  it  is  true,  abolish  all  respiratory  discharges,  but  converts  the 
rhythmic  respirations  into  a  series  of  inspiratory  spasms  which  are 
repeated  at  long  intervals  and  are  entirely  inadequate  for  the  proper 
aeration  of  the  blood.  According  to  Sherrington  a  repetition  on  the 
mammal  of  Hering's  experiment  does  not  lead  to  the  same  results,  since 
a  spasmodic  discharge  is  produced  from  the  isolated  spinal  cord  as  a 
result  of  asphyxia.  But  it  is  doubtful  whether  in  this  case  there  was 
not  some  continuous  excitation  of  the  cord  going  on,  as  a  result  of  the 
closure  of  the  demarcation  current  in  the  cut  ends  of  the  posterior  roots 
by  the  body  fluids.  It  is  possible  that  the  nem-ons  possess  some 
automatic  power,  i.e.  some  power  of  initiating  nervous  processes, 
as  a  result  of  changes  in  the  fluids  surrounding  them.  This  auto- 
maticity,  however,  is  not  a  prominent  feature  of  the  nervous  system, 
which  has  been  evolved  as  a  purely  reactive  mechanism  to  the 
afferent  impulses  resulting  from  the  material  changes  continually 
taking  place  in  the  environment  of  the  animal. 


SECTION  VI 


STRUCTURE  OF  THE  SPINAL  CORD 

In  the  higher  representatives  of  the  invertebrate  class  the  central 
nervous  system  consists,  as  we  have  seen,  of  a  chain  of  gangha,  each 
ganglion  or  pair  of  ganglia  presiding  over  the  reactions  of  its  own  seg- 
ment, but  connected  by  long  paths  with  the  other  gangha  and  with  the 
head  gangha.  The  latter,  being  especially  developed  in  connection 
with  the  organs  of  special  sense  which  are  projicient  in  function,  acquire 
a  control  over  the  rest  of  the  ganglia  (Fig.  154).     The  vertebrate  spinal 


DORSAL 


Spinal   canal 


NeuT-eate 


=  o-,aZ 


^    •  I  t  Jnf.   Br       •^J^(^'''^c-  ,    r       ,       c  i     i      »r 

^    3y     \/  \\V j.-V^'^  Opiaal  Lord  •  Oejmeatal     iVe 

iajundibulum  VENTR4L 


Anus 


DORSAL 


/    UbiopKaaus 


VENTRAL 


Fig.  154  Vertebrate  central  nervous  system  compftred  with  that  of  the  arthropod. 
(Gaskell.)  (Note  that  according  to  Gaskell  the  ventricles  of  the  brain  and  the 
primitive  neural  canal  correspond  to  the  invertebrate  stomach  and  intestine.) 

cord  may  be  looked  upon  as  a  chain  of  gangUa  which  have  become  fused 
concurrently  with  a  diminution  in  the  importance  of  the  local  seg- 
mental reactions  and  with  a  growth  in  the  sohdarity  of  the  whole 
system  ;  so  that  in  the  higher  vertebrates,  at  any  rate,  little  trace  of  the 
primitive  segmental  arrangement  is  evident  in  the  internal  structure 
of  the  cord.  Some  remains  of  this  arrangement  still  persist,  however, 
in  the  origin  from  the  cord  of  nerve-roots,  which  are  distributed  roughly 
within  the  area  of  the  corresponding  segment  of  the  body. 

In  man  the  spinal  cord  is  an  elongated  cylindrical  struttm-e  slightly 
flattened  from  before  backwards  and  about  eighteen  inches  long.     It 

365 


356  PHYSIOLOGY 

gives  off  a  series  of  nerve-roots,  which  are  arranged  in  thirty-one  pairs 
and  are  distributed  symmetrically  to  the  two  sides  of  the  body.  Each 
nerve  arises  by  two  roots,  an  anterior  and  a  posterior,  the  anterior 
being  composed  of  a  series  of  rootlets  spread  over  a  considerable 
area  of  the  cord,  while  the  posterior  roots  arise  as  a  compact  bundle 
from  a  groove  on  the  postero- lateral  aspect  of  the  cord.  The  posterior 
nerve-roots  pass  through  a  ganglion  and  join  the  anterior  roots  in  the 
intervertebral  foramina  to  form  the  mixed  nerve.  On  section  the  cord 
is  seen  to  consist  of  a  core  of  gxey  matter  surrounded  on  all  sides  by 
white  matter.  The  white  matter  is  made  up  of  medullated  nerve  fibres 
which  are  devoid  of  a  neurilemma,  and  run  within  tunnels  or  tubes  in 
the  supporting  neuroglia.  The  grey  matter  has  roughly  the  form  of 
a  letter  H,  and  consists,  in  cross-section,  of  a  comma-shaped  mass 
on  each  side  of  the  cord,  joined  across  the  middle  line  by  a  band  of  grey 
matter.  On  the  anterior  aspect  of  the  cord  is  a  furrow,  the  anterior 
fissure,  which  contains  a  process  of  the  enveloping  membrane  of  the 
cord,  the  pia  mater,  and  is  limited  at  its  bottom  by  a  band  of  white 
matter,  the  anterior  white  commissure,  which  unites  the  anterior 
columns  of  white  matter. 

On  the  hinder  aspect  of  the  cord  is  another  fissure,  the  posterior 
fissure,  which  is  very  narroAV  and  is  built  up  chiefly  by  neuroglia.  A 
third  fissure  at  the  point  of  origin  of  the  posterior  nerve-roots  serves  to 
divide  the  white  matter  of  the  cord  into  an  antero- lateral  column  and  a 
posterior  column,  and  the  former  is  imperfectly  separated  by  the 
spread-out  anterior  rootlets  into  anterior  and  lateral  columns.  The 
cord  in  cross-section  (Fig.  155)  is  circular  in  the  dorsal  region  and  oval  in 
the  cervical  and  lumbar  regions.  It  presents  two  marked  enlargements, 
namely,  the  cervical  enlargement,  corresponding  to  the  outflow  of  the 
nerves  going  to  the  upper  limb,  and  the  lumbo-sacral  enlargement, 
which  gives  off  the  nerves  to  the  lower  limb.  In  the  sacral  region  it 
rapidly  tapers  off  to  a  blunt  point.  In  the  centre  of  the  band  of  grey 
matter,  connecting  the  two  masses  on  each  side  of  the  middle  line,  is  the 
central  canal  of  the  cord,  the  remains  of  the  primitive  neural  canal  of 
the  embryo.  The  grey  matter  in  front  of  it  is  called  the  anterior  grey 
commissure,  that  behind  the  posterior  grey  commissure.  The  comma- 
shaped  mass  of  grey  matter  on  each  side  of  the  cord  presents  in  front 
the  broad  anterior  cornu,  and  behind  the  narrower  posterior  cornu, 
which  extends  up  to  the  postero- lateral  groove  in  the  line  of  emergence 
of  the  posterior  roots.  In  the  dorsal  region  of  the  cord  the  grey  matter 
projects  into  the  lateral  column  of  white  matter  to  form  the  lateral  horn. 
The  grey  matter  consists  of  a  supporting  tissue  of  neurogha  in  which 
are  embedded  nerve-cells  and  their  processes  and  the  endings  of  nerve 
fibres.  The  neuroglia  is  formed  of  a  thick  felt- work  of  fibres  with  here 
and  there  nuclei  applied  to  the  fibres.     Occasionally  we  may  meet 


STRUCTURE  OF  THE  SPINAL  CORD 


:\ra 


Cervical. 


Dorsal 


Lumbar 


.,,  >V^ 


^-r 


/ 


\ 


ANT 
KOOT-BUNDLtS 


e,  middle  group  of  CO  «,;.^    ■  commissure, 

horn;    cc,  ccutral  canal,    at. 


358 


PHYSIOLOGY 


cells  provided  with  a  very  large  number  of  branches  and  representing 
the  cells  from  which  all  the  fibres  of  the  nem-oglia  have  been  derived. 
The  neuroglia  is  present  in  specially  large  amount  in  two  situations, 
namely,  immediately  around  the  central  canal  and  as  a  capsule  to  the 
enlargement  of  the  posterior  cornu,  known  as  the  head  or  caput  comu 
fosterioris.  In  this  latter  situation  the  neuroglia  contains  a  large 
number  of  small  richly  branched  nerve-cells  and  is  spoken  of  as  the 
substantia  gelatinosa  of  Rolando.  The  nerve-cells  are  arranged  in 
distinct  groups.  In  the  anterior  horn  we  may  distinguish  three 
groupS;  a  median  group  of  cells  near  the  middle  line,  many  of  which 


Ant.  lat i 

asc.  tract 


Direct 
Cei-ebellar  X'py^m 


Posfeiio!' Hoots 
wHhcoUaiemls. 


Fig.  156.     Spinal  cord.   {After  Lenhossek.)    On  left  side  of  figure  are  shown 
the  nerve-cells  with  their  axis-cylinder  processes.    On  the  right  side  the 
distribution  of  the  chief  collaterals. 
1,  motor  cells  ;  2,  cells  of  the  columns  ;  2a,  cells  of  Clarke's  columi],  sending 

processes  across  into  direct  cerebellar  tract ;  3,  4,  and  5,  commissural  cells. 

send  their  processes  across  to  the  other  side  in  the  anterior  white  cornu, 
and  an  external  group  often  subdivided  into  a  postero- external  and 
an  antero- external.  The  latter  group  is  especially  developed  in  the 
regions  of  the  cervical  and  lumbar  enlargements  and  consists  of  very 
large  multipolar  cells  with  many  dendrites  which  send  their  axons 
into  the  anterior  roots  and  by  these  to  the  muscles  of  the  limbs. 
Another  group  of  rather  smaller  cells  is  found  in  the  lateral  horn,  in 
that  region  of  the  cord  where  this  is  marked.  A  very  definite  group 
of  cells  may  be  seen  in  the  dorsal  region  of  the  cord  in  the  inner  aspect  of 
the  root  of  the  posterior  horn.  This,  which  is  known  as  Clarke's 
column,  is  formed  by  large  cells  elongated  in  the  longitudinal  direction 
of  the  cord.  Besides  these  definite  colimins  a  number  of  nerve-cells 
are  distributed  irregularly  through  the  grey  matter,  especially  of  the 
posterior  horn.  According  to  the  destiny  of  their  axons  these  nerve- 
cells  may  be  divided  into  four  groups  (Fig.  156). 


STRUCTURE  OF  THE  SPINAL  CORD  359 

(1)  THE  MOTOR  CELLS,  the  largest  of  all,  which  send  their  axons 
into  the  anterior  roots,  where  they  run  to  supply  skeletal  muscle  fibres. 
As  a  sub-group  of  these  cells  we  may  class  the  somewhat  smaller  cells 
of  the  lateral  horn,  which  in  all  probability  send  their  axons  by  the 
anterior  roots  to  supply  visceral  muscles.  Their  axons  can  be  dis- 
tinguished from  the  motor  axons  by  the  smaller  diameter  of  the  nerve 
fibres  they  form.  They  pass  later  from  the  mixed  nerve  along  a 
white  ramus  communicans  into  the  sympathetic  system,  in  the  gangUa 
of  which  they  end. 

(2)  CELLS  OF  THE  COLUMNS.  As  typical  of  these  cells  we  may 
take  those  which  form  Clarke's  column.  Their  axons  do  not  leave 
the  central  nervous  system,  but  pass  out  into  the  white  matter  to  some 
other  part  of  the  central  nervous  system,  contributing  thus  to  form  the 
white  columns  of  the  cord. 

(3)  COMMISSURAL  CELLS.  These  cells  send  their  axon  across 
the  middle  line  to  the  opposite  side  of  the  cord,  making  up  a  great  part 
of  the  anterior  white  commissure. 

(4)  CELLS  OF  GOLGL  These  cells  are  found  chiefly  in  the  posterior 
horn.  They  are  multipolar  and  are  distinguished  from  all  the  other 
cells  by  the  fact  that  their  axon  does  not  pass  far  from  the  cell,  but 
rapidly  breaks  up  into  a  number  of  branches  which  terminate  in  the 
near  neighbourhood  of  the  cell  giving  ofi  the  axon.  They  may  be 
regarded  as  association  cells,  i.e.  as  ser\'ing  to  establish  a  functional 
connection  between  many  different  cells  at  any  given  level  of  the  grey 
matter. 

The  white  matter  of  the  cord  is  divided  by  the  fissures  already 
described  into  anterior,  lateral,  and  posterior  columns.  The  nerve 
fibres  of  which  it  is  composed  are  all  of  them  axons  of  nerve-cells 
situated  at  different  levels  of  the  central  nervous  system  or  outside 
the  cord.  Since  the  whole  object  of  the  study  of  the  anatomv  of 
the  cord  is  the  tracing  out  of  the  systems  of  neurons  of  which  it  is 
made  up,  and  therefore  of  the  possible  paths  of  any  reflexes  or  nerve 
impulses  through  the  cord,  a  mere  anatomical  differentiation  of 
different  columns  is  quite  useless  unless  we  can  determine  in  each 
column  the  origin  and  destination  of  the  fibres  of  which  it  is  com- 
posed. For  tracing  out  the  course  of  the  different  axon  systems  in 
the  central  nervous  system  several  methods  are  available. 

(rt)  HISTOLOGICAL.  Two  methods  may  be  employed  for  staining 
a  nerve-cell  with  all  its  processes,  namely,  the  intravitam  staining 
with  methylene  blue  and  the  impregnation  method  invented  by 
Golgi.  In  the  latter  method,  of  which  there  are  many  modifications, 
the  nervous  tissue  is  hardened  in  some  chromate  or  bichromate, 
and  is  then  soaked  in  a  solution  of  silver  nitrate  or  mercuric  chloride. 
In  this  way  a  precipitate  of  silver  or  mercuric  chromate  is  formed 


360 


PHYSIOLOGY 


within  the  nerve-cells  and  their  processes ;  but  for  some  unexplained 
reason  the  impregnation  is  not  general,  and  is  confined  to  a  small 
percentage  of  the  neurons.  If  the  precipitate  were  diffuse,  even  a 
thin  section  would  be  absolutely  opaque  ;  since  it  is  partial,  thick 
sections  may  be  cut  and,  after  clearing,  allow  the  tracing  of  the 
processes  of  the  few  impregnated  nerve-cells  through  the  whole 
thickness  of  the  section.  We  may  in  this  way  get  sections  0-1  mm. 
thick  at  the  point  of  entrance  of  a  posterior    nerve-root  and  trace 

out  the  course  and  ending  of  a  large 
number  of  the  fibers  composing  the 
nerve-root,  or  we  may  in  a  section 
involvmg  the  anterior  nerve- root  trace 
the  course  of  an  axon  of  an  anterior 
cornual  cell  out  of  the  cord  into  the 
root.  This  method  is  of  no  use  in 
tracing  any  given  nerve  fibre  through 
the  whole  length  of  the  cord.  For 
this  purpose,  however,  several  methods 
are  available. 

(h)  MYELINATION  METHOD  OF 
FLECHSIG.  Nerve  fibres  at  their  first 
formation  as  axons  of  a  nerve- cell 
are  non-medullated,  the  medullary 
sheath  being  formed  later  with  the 
beginning  of  function  of  the  nerve. 
It  has  been  shown  by  Flechsig  that 
the  myelination  does  not  occur  simul- 
taneously through  all  parts  of  the 
central  nervous  system,  but  that  it  is 
later  in  proportion  as  the  nerve  fibre  is 
more  recent  in  the  phylogenetic  history  of  the  animal.  The  cord  in  its 
most  primitive  form  can  be  regarded  as  a  series  of  ganglia  presiding 
over  the  different  segments  of  the  body.  The  most  primitive  fibres 
therefore  would  be  those  which  run  from  the  periphery  of  the  body 
to  each  segment  and  from  each  segment  out  to  the  muscles,  and 
so  a  medullary  sheath  is  first  formed  in  a  number  of  the  fibres  entering 
and  leaving  the  cord  in  the  nerve-roots.  Next  in  order  of  myelina- 
tion are  those  fibres  which  connect  different  segments  of  the  cord, 
the  internuncial  or  intra-spinal  fibres.  Next  come  those  fibres 
which  connect  the  spinal  cord  with  the  cerebellum.  Last  of  all 
to  receive  a  medullary  sheath  are  the  fibres  which  take  a  direct 
course  from  the  cerebral  cortex  to  the  spinal  cord.  These  are  called 
the  pyramidal  tracts,  and  in  man  are  not  medullated  until  the  first 
month  after  birth  (Fig.  157). 


Fig.  157.     Section  through  the  cer- 
vical  spinal    cord   of   a  new-born 
child,  stained  by  Weigert's  method, 
to  show  absence  of    medullation 
in  pyramidal  tract. 
ca,     anterior    commissure ;      Fp, 
crossed  pyramidal  tract ;    Fe,  direct 
cerebellar  tract  ;  Zrp,   posterior  root 
zone  ;      rp',     posterior     root -fibres. 
(Bechterew.) 


STRUCTURE  OF  THE  SPINAL  CORD  361 

(c)  THE  WALLERIAN  METHOD.  A  nerve  fibre,  when  cut  ofE 
from  the  nerve-cell  of  which  it  is  a  process,  degenerates.  This 
degeneration  is  marked  by  a  breaking  up  of  the  medullary  sheath 
and  a  conversion  of  the  phosphorised  fat,  myelin,  of  which  it  is 
composed,  into  ordinary  fat.  Later  on  the  fat  is  absorbed  and  the 
nerve  becomes  replaced  by  a  strand  of  fibrous  tissue  in  the  case  of 
peripheral  nerves,  of  neurogha  in  the  central  nervous  system.  If 
the  white  matter  of  one  half  of  the  spinal  cord  be  divided  in  the  dorsal 
region,  and  the  animal  be  killed  about  three  weeks  after  the  operation, 
sections  of  the  cord  both  above  and  below  the  lesion  will  show  the 
presence  of  degenerated  fibres.  In  order  to  display  these  fibres 
pieces  of  the  cord  are  hardened  in  a  solution  containing  bichromates 
and  are  then  immersed  in  a  mixtiure  of  osmic  acid  and  bichromate. 
By  this  method  ordinary  fat  is  stained,  but  myelin  is  left  unstained 
(Marchi's  method).  Degenerated  fibres  are  therefore  stained  black 
in  virtue  of  their  content  in  fat.  The  black  staining  has  different 
distribution  according  as  we  take  a  section  of  the  cord  above  or 
below  the  lesion.  The  existence  of  the  degeneration  shows  that  those 
fibres  which  are  degenerated  in  the  cervical  region  are  axons  of 
nerve-cells  situated  below  the  lesion,  while  the  fibres  in  the  lumbar 
cord  which  are  degenerated  must  have  their  nerve-cells  in  some  part 
of  the  nervous  system  which  is  above  the  lesion.  If  the  animal  be 
kept  alive  for  a  considerable  time,  six  months  or  more,  before  being 
killed,  the  occurrence  of  degeneration  in  any  given  area  of  the  cord 
will  be  shown  by  the  absence  of  normal  nerve  fibres  in  this  area. 
In  such  a  case  some  method  of  staining  the  medullary  sheath,  such 
as  that  of  Weigert  or  Heller,  is  employed,  when  the  degenerated 
area  will  be  evident  owing  to  its  inability  to  take  the  stain.  This 
method,  however,  is  not  so  satisfactory  as  the  Marchi  method,  since 
it  is  impossible  in  this  way  to  detect  in  a  section  the  presence  of  one 
or  two  degenerated  nerve  fibres,  whereas  by  the  use  of  the  Marchi 
method  they  would  appear  as  black  dots  in  the  unstained  section 
{rp.  Fig.  10.")). 

{d)  METHOD  OF  RETROGRADE  DEGENERATION.  When  a 
nerve  fibre  is  divided  there  is  nq  degeneration  as  a  rule  in  the  part 
of  the  nerve  fibre  central  to  the  lesion.  The  nerve-cell  is,  however, 
affected,  and  the  extent  to  which  this  occurs  is  more  pronounced 
according  as  the  lesion  is  nearer  to  the  cell  (Fig.  158).  If,  for  instance, 
an  anterior  root  be  divided  and  three  weeks  later  the  animal  be  killed 
and  sections  made  of  the  corresponding  segment  of  the  cord  and 
stained  with  toluidine  blue  or  methylene  blue,  a  striking  difference 
will  be  observed  between  the  cells  of  the  anterior  horn  of  the  two 
sides  of  the  cord.  On  the  side  of  the  lesion  the  nucleus  of  the 
cells  will  be  somewhat  swollen,  and  may  be  displaced  towards  the 


362 


PHYSIOLOGY 


periphery  of  the  cell.  The  Nissl  granules  are  no  longer  distinct,  but 
the  whole  cell  is  diffusely  stained  blue.  In  some  cases  this  change 
may  go  on  to  complete  atrophy  of  the  cell  and  consequent  degenera- 
tion of  the  whole  of  its  axon.  Generally,  however,  the  cell  gxadually 
recovers,  so  that  six  months  after  the  lesion  no  difference  will  be 
observable  between  the  cells  on  the  two  sides  of  the  cord.  This 
method  must  be  used  with  some  caution  as  a  means  of  tracing  out 


Fig.  158.     Cells  from  the  oculo-motor  nuclei  thirteen  days  after  section 

of  the  nerve  on  one  side. 

a,  cell   from    healthy   side ;    6,  cell   from    side   on   which  nerve   was 

divided.     (Flatatj.) 

the  connections  of  any  given  neurons  in  the  central  nervous  system, 
since  it  has  been  shown  by  Warrington  that  somewhat  similar  changes 
may  be  produced  in  the  anterior  horn- cells  by  division  of  the  posterior 
roots,  thus  cutting  off  those  impulses  by  which  their  activity  is 
normally  excited.  Here  we  have  a  lesion  applied  to  one  neuron 
exciting  a  histological  change  in  the  cell  body  of  another  neuron 
which  is  next  in  the  chain  of  the  nervous  arc. 

The  structure  of  the  cord  is  closely  connected  with  and  determines 
its  twofold  function,  namely,  as  a  series  of  reflex  centres  for  the 
different  segments  of  the  body,  and  as  a  means  of  communication 
between  the  trunk  and  limbs  and  the  higher  parts  of  the  central 
nervous  system.  An  examination  of  the  relative  area  of  the  white 
matter  at  different  levels  of  the  cord  shows  a  steady  increase  from 
the  lower  to  the  upper  end.  The  increase  is  not,  however,  pro- 
portional to  the  number  of  fibres  which  enter  or  leave  the  cord  in 
the  various  spinal  nerve-roots.  Of  these  fibres  .therefore  a  certain 
proportion  are  destined  to  serve  merely  the  local  segmental  reflexes, 
while  others  are  continued  directly  upwards  to  the  brain  or  are  con- 
nected with  cells  which  themselves  send  their  axons  up  to  the  brain 


STRUCTURE  OF  THE  SPIN'AL  CORD  363 

(cells  of  the  columns).  All  the  motor  fibres  in  the  nerve-roots  arise 
from  cells  in  the  spinal  cord  near  the  point  of  origin  of  the  root. 
Any  direct  influence  of  the  brain  on  the  motor  mechanisms  of  the 
body  is  therefore  effected  through  the  intermediation  of  the  seg- 
mental neural  mechanisms  of  the  grey  matter  of  the  cord.  We  will 
consider  the  function  and  related  structure  of  the  cord  in  these  two 
aspects :  first,  as  a  reflex^  centre,  and,  secondly,  as  a  conductor  of 
impulses  to  the  higher  parts  of  the  central  nervous  system 


SECTION  VII 

THE  SPINAL  CORD  AS  A  REFLEX  CENTRE 

In  the  evolution  of  the  cord  the  primitive  segmental  arrange- 
ment has  been  esiDecially  interfered  with  by  the  development  of  the 
four  limbs.  Since  the  reactions  of  the  limbs  transcend  in  importance 
and  complexity  those  of  the  rest  of  the  body,  a  great  enlargement 
of  the  cord  has  occurred  in  the  region  of  the  nerve-roots  which  supply 
the  limbs.  Each  limb  must  be  considered  as  produced  by  the 
fusion  of  a  number  of  body  segments,  in  which  the  morphological 
segmental  arrangement  has  entirely  given  place  to  a  physiological 
one.  Thus  no  single  muscle  of  the  limbs  is  innervated  from  one 
nerve-root,  every  muscle  being  formed  from  elements  belonging  to 
several  segments  and  innervated  from  several  nerve-roots.  The 
segmental  arrangement  of  the  cord  is  hidden  moreover  by  the 
increasing  complexity  of  the  spinal  reflexes  and  the  consequent  involve- 
ment of  many  segments  in  even  the  simplest  reactions.  As  we  shall 
see  later,  practically  no  reflex  can  be  evoked,  even  by  stimulation  of 
one  nerve  fibre  or  nerve-root  in  any  of  the  vertebrata,  which  does 
not  involve  in  its  response  elements  belonging  to  many  segments. 

Since  the  reactions,-  which  can  be  carried  out  by  any  part  of  the 
nervous  system,  depend  on  the  neurons  of  which  the  part  is  composed, 
it  is  necessary,  before  treating  of  the  reactions  of  the  spinal  animal, 
|,to  consider  the  "  way  in  "  to  and  the  "  way  out  "  of  the  centre,  as  well 
as  the  connections  between  the  entering  and  issuing  paths.  Each 
segment  of  the  cord  gives  off  a  pair  of  nerve-roots,  subdivided  into 
an  anterior  and  a  posterior  root  (Fig.  159).  In  mammals  it  is  easy 
to  show  that  the  posterior  root  is  exclusively  afferent  in  function. 
Section  of  the  root,  either  distal  or  proximal  to  the  ganglion,  produces 
no  paralysis  of  any  description.  It  may  cause  diminished  sensation 
in  the  area  supplied  by  it,  and  if  two  or  three  adjacent  posterior  roots 
be  divided,  complete  anaesthesia  results  in  the  central  part  of  the 
skin  area  supplied  from  these  roots.  Stimulation  of  the  central  end 
of  a  divided  posterior  root  evokes  in  a  conscious  animal  signs  of  pain. 
In  an  animal  possessing  only  spinal  cord  and  bulb,  reflex  effects  are 
produced,  i.e.  movements  of  skeletal  muscles  as  well  as  effects  on 
visceral  muscles,  such  as  constriction  of  blood-vessels,  relaxation 
of  intestinal  muscle,  and  so  on.     On  the  other  hand,  section  of  an 

364 


THE  SPINAL  CORD  AS  A  REFLEX  CENTRE 


305 


anterior  root  causes  paralysis  of  muscles  or  parts  of  muscles.  Section 
of  all  the  anterior  roots  going  to  a  limb  will  produce  complete  motor 
paralysis  of  the  limb.  Stimulation  of  the  central  end  of  a  divided 
anterior  root  has  no  effect.  Stimulation  of  the  peripheral  end  evokes 
contraction  of  muscles,  and  if  the  root  experimented  on  be  in  the 
upper  dorsal  region  of  the  cord,  certain  visceral  effects,  e.fj.  dilatation 
of  the  pupil  or  augmentation  of  the  heart  beat,  may  result. 

To  this  general  law,  the  law  of  Bell  and  Magendie,  which  affirms  the  purely  ^ 
afferent  function  of  the  posterior  roots  and  the  purely  efiFerent  function  of  the 
anterior  roots,  certain  exceptions  must  be  noted.  In  the  first  place,  in  the 
lower  vertebrata  the  separation  of  afferent  from  efferent  fibres  seems  to  be 
not  so  complete  as  in  the  higher  vertebrates.  Thus  in  the  chick  Cajal  and 
others  have  described  fibres  given  off  as  axons  from  the  cells  of  the  grey  matter 


159.      Figures  (from  Yeo)  to  illustrate  the  degree  and  direction  of 
degeneration  as  a  result  of  section  of  the  spinal  roots. 
I,  division  of  whole  nerve  below  ganglion.     II,  division  of  anterior  root. 
Ill,  division  of  posterior  root   above  ganglion.     IV,  division  of  posterior 
root  above  and  below  gangUon. 


and  leaving  the  cord  by  the  posterior  root.  The  function  of  these  fibres  is 
unknown.  In  the  frog  Steinach  has  stated  that  ^^sceral  effects  maj'  ensue 
on  stimulation  of  the  lower  posterior  roots.  This  statement  is  controverted 
by  Horton-Sniith,  who,  however,  has  noticed  contractions  of  fibres  of  voluntary' 
muscles  as  the  result  of  stimulating  these  roots. 

In  a  class  by  themselves  wc  must  place  the  vasodilator  effects  observed 
by  Strieker,  Dastre  and  Morat,  and  Bayliss  to  follow  excitation  of  the  peri- 
pheral ends  of  the  posterior  roots.  Bayliss  has  showii  that  the  fibres,  tlirough 
which  the  vasodilatation  is  produced,  must  have  their  cell-station  in  the  posterior 
root  gangUa.  It  seems  therefore  that  the  same  filjres  provide  for  carrying  both 
afferent  impulses  from  skin  to  cord,  and  vasodilator  inipiUses  from  the  cord 
to  the  vessels  of  the  skin.  Bayliss  has  designated  the;  impulses  whith 
effect  the  vasodilatation  as  antidromic,  since  tliey  arc  opposed  in  direction  to 
the  normal  impuLscs  of  the  nerve  fibre.  Of  the  same  nature  arc  the  curious 
trophic  impulses  which  extend  along  the  posterior  roots  and  which  must  conu> 
into  play  when  eruptions  of  erythema  or  herpes  occur  as  the  result  of  inflammation 
or  h;emorrhages  in  the  substance  of  the  posterior  root  ganglia.  Both  these 
phenomena  an;  at  present  but  imperfectly  understood  ;  and  their  anomalous 
character  is  only  intensified  by  the  further  fact  elicited  by  Bayliss.  viz.  that 
it  is  possible,  by  stinuilation  of  afferent  nerves,  to  excite  reflexly  vasodilatation 
through  the  intermediation  of  the  posterior  roots.  Unless  this  reflex  dihita- 
tion  is  simply  an  example  of  an  'axon    reflex'  (''.  p.  •">3i))  it    would   furnish 


360 


PHYSIOLOGY 


an  exception  to  the  otherwise  universal  law  of  forward  direction  in  the  mam- 
malian nervous  system. 

A  third  exception  to  the  law  of  Bell  and  Magcndie  is  only  apparent.  It 
is  sometimes  found  that  excitation  of  the  peripheral  end  of  a  divided  anterior 
root  gives  rise  to  manifestations  of  pain  or  to  reflex  movement.     This  has  been 

shown  by  Scliiflf  to  be  due  to  the  presence, 
in  the  sheaths  of  the  anterior  roots,  of  fine 
fibres  derived  from  the  posterior  roots  and 
taking  a  recurrent  course  to  end  probably  in 
the  membranes  of  the  cord.  This  recmrent 
sensibility  is  at  once  abolished  by  section  of 
two  or  three  adjacent  posterior  roots. 


THE  WAY  IN 
We  may  now  consider  the  possible 
ways  open  to  a  nerve  impulse  entering 
the  cord.  Each  posterior  root  on  entering 
the  cord  divides  into  two  bundles.  The 
smaller  bundle  passes  to  the  outer  side 
of  the  tip  of  the  posterior^ horn,  where 
its  fibres  bifurcate  (Fig.  160),  giving  rise 
to  fibres  which  pass  up  and  down  the 
cord  in  a  small  longitudinal  band  of  fibres 
known  as  Lissauer's  tract.  The  fibres  run 
only  a  short  distance  before  turning  into 
the  grey  matter,  and  terminate  in  arbori- 
sations round  the  cells  of  the  substantia 
gelatinosa  in  the  head  of  the  posterior 
horn.  By  far  the  greater  number  of  the 
posterior  root-fibres  pass  to  the  inner  side 
of  the  posterior  horn  into  Burdach's  or 
the  postero- external  column.  Here  they 
also  divide  into  two  main  branches,  one 
running  up  and  the  other  down  in  the 
white  matter.  The  descending  branch 
passes  through  two  or  three  segments 
before  turning  into  the  grey  matter  of 
the  posterior  horn  of  a  lower  segment. 
Of  the  ascending  branches,  some  end  at 
different  levels  of  the  cord,  but  a  certain 
proportion  of  the  fibres  from  every 
root  traverse  the  whole  length  of  the  cord  in  the  posterior  columns 
to  terminate  in  the  posterior  column  nuclei  (nuclei  gTacilis  and 
cuneatus)  in  the  medulla  oblongata.  As  we  proceed  up  the  cord 
the  entering  posterior  root  fibres  displace  the  long  fibres  of  those 
below  towards  the  middle  line,  so  that  in  a  section  through  the  cord 


~s        o~ — 

Fig.  16U.  Longitudinal  section 
of  spinal  cord  of  chick,  showing 
bifurcation  of  dorsal  root- 
fibres,  and  the  passage  of  their 
collaterals  into  the  grey  matter. 
Three  cells  of  the  dorsal  horn 
are  also  seen  sending  their 
axons  into  the  dorsal  (jolumns. 
(Cajal.) 


THE  SPINAL  CORD  AS  A  REFLEX  CENTRE 


361 


ill  the  upper  cervical  region  the  posterior  median  column,  or  column 
of  Goll,  is  made  up  almost  exclusively  of  fibres  from  the  hind  limb, 
while  the  column  of  Burdach  consists  of  fibres  from  the  fore  limb. 

Besides  these  distant  connections,  every  entering  nerve  fibre 
makes  connection  with  all  parts  of  the  grey  matter  in  and  about  its 
level  of  entrance  by  means  of  collaterals  (Fig.  161).  Five  groups 
of  these  collateral  branches  can  be  distinLiiished,  i.e., 

(1)  Fibres  which  arborise 
round  cells  in  the  posterior 
horn  of  the  same  side. 

(2)  Fibres  which  pass 
through  the  dorsal  grey  com- 
missure to  the  grey  matter  of 
the  opposite  side  of  the  cord. 

(3)  Fibres  terminatinu" 
round  the  median  group  of 
cells  of  the  anterior  horn. 

(4)  Fibres  \yhich  end  in  a 
rich  basket-work  round  the 
cells  of  Clarke's  column. 

(5)  The  sensori  -motor 
bundle,  which  passes  forwards 
through  the  grey  matter  to 
end  round  the  cells  in  the 
anterior  horn  of  the  same  side 
of  the  cord. 


1% 


Each  entering   posterior  root 

fibre,  besides  these  collaterals  in 

the  neighbourhood  of  its  entrance, 

gives  but  few  to  higher  segments   Fig.  161 

of  the  cord  before   it   terminates 

in  the   posterior    column    nuclei. 

Sherrington  suggests  that  the  cells   ^^^^\  ^?™"  ' 
?.  7         f  •        au         ^'  substance 


Chief  collaterals   of   dorsal  column 
fibres  from  new-born  mouse.     (Cajal.) 
A,  intermediate  nucleus  ;    B,  anterior  (ven- 


c,  dorsal    or 
of  Rolando. 


posterior     cornu 


of  Clarke's  column  receive  fibres 

mainly    from  the    ascending 

branches  of  the  nerve  roots  from  the  posterior  hmb,  a  corresponding  station 

for  the  nerve  fibres  of  the  anterior  limb  being  represented  by  the  cells  of  the 

nucleus  ciuieatus. 

That  several  different  systems  of  fibres  are  included  in  these 
roots  is  shown  by  the  different  period  at  which  they  acquire  their 
myelin  sheath.  Among  the  earliest  to  acquire  a  sheath  are  the 
fibres  which  end  in  the  posterior  horn  and  those  which  pass  to  the 
anterior  horn,  while  the  long  fibres  in  the  dorsal  columns  do 
not  become  medullated  until  much  later  in  foetal  life.  Since  the 
nerve  fibres  of  the  central  nervous  system  do  not  become  functional 


368  PHYSIOLOGY 

until  they  have  acquired  a  medullary  sheath,  we  must  conclude  that 
the  reflex  responses  affecting  the  segment  in  which  the  fibres  enter 
are  developed  earlier  than  those  which  involve  also  the  activity 
of  the  cerebellum  and  medulla. 

The  primitive  segmental  character  of  the  central  nervous  system 
is  retained  in  its  pure  form  only  in  the  segmentation  of  the  dorsal 


Fig.  162.  Transver.se  section  of  spinal  cord,  showing  collaterals  terminating 
in  a  rich  arborisation  round  the  cells  of  Clarke's  column  (a,  b),  as  well 
as  others  passing  to  the  anterior  cornua,  and  through  the  commissures. 
(Cajal.) 


spinal  root  ganglia.  Each  of  these  ganglia  or  afferent  roots  consists 
of  the  fibres  from  the  sense-organs  in  a  segmental  area  of  the  body 
surface  as  well  as  from  the  muscular  and  visceral  apparatus  in  the 
same  segment.  Section  of  one  dorsal  posterior  nerve-root  will  cause 
a  diminution  of  sensibility  over  a  band-like  area  corresponding  to 
the  distribution  of  the  fibres  of  the  root,  though  to  produce  complete 
insensibility  the  two  adjacent  nerve-roots  must  be  divided,  in  con- 
sequence of  the  overlap  of  fibres  at  the  periphery.  In  the  limbs 
the  segmental  distribution  of  the  sensory  fibres  is  made  out  with 
more  difl&culty.  Each  limb  must  be  regarded  as  made  up  from 
a  series  of  fused  segments,   from   five  to  seven   in   number.      The 


THE  SPIN'AL  CORD  AS  A  REFLEX  CEN'TRE 


309 


accompanying  diagram  (Fig.  163)  from  Sherrington  shows  the  manner 
in  which  the  skin  fields  of  these  segments  are  combined  to  make  up 
the  total  skin  area  in  the  hind  limb  of  the  monkev^ 

THE  WAY  OUT 
Primitively  the  motor  nerves  also  represent  fibres  passing  from 
a  collection  of  ganglion- cells  to  the  muscles  of  the  corresponding 
body  segment.  In  the  dorsal  region  this  segmental  arrangement 
of  motor  nerve  fibres  is  still  traceable  in  the  adult  animal. 
In  all  other  parts  the  morphological  has  become  subservient  to  a 
physiological  arrangement.  Every  muscle  of  the  limbs  contains 
elements  from    several  segments,   and  is  innervated  therefore  from 


J^  ,_«  „„M„,.i„i),.H.iiiiiiiiiniii)jn.,..ri;!,!Minijyu;n:nlMnilllJi:!li-nM  riillllilllll  rilLl.jnTTTTgpmga:*-^    He^ri 


;  12       I!   ■     'O 


le^eL  '^  Ohe,  /y^tf^- 


ijweL  of  'Jie  arOdjs, 


several  anterior  spinal  roots.  Hence  it  follows  that  stimulation  of 
one  anterior  root  produces  no  definite  movement  .of  a  group  of  muscle.>-, 
but  partial  contraction  of  a  number  of  muscles  which  do  not  normallv 
contract  simultaneously.  Thus  stimulation  of  a  sensory  nerve  may 
evoke  either  flexion  or  extension  of  a  limb,  but  not  both  simultaneously. 
Stimulation  of  the  motor  roots  will  cause  simultaneous  contraction 
of  both  flexor  and  extensor  muscles.  It  is  this  subordination  of 
morphological  to  physiological  arrangement  in  the  limbs  which 
has  necessitated  the  formation  of  limb  plexuses.  The  nerve-root 
is  a  morphological  collection  of  fibres  ;  the  nerve  issuing  from  a 
limb  plexus  and  passing  to  a  group  of  muscles  is  a  physiological 
collection.  When  it  is  stimulated  it  evokes  a  contraction  of  a  group 
of  muscles  which  are  normally  synergic,  i.e.  co-operate  in  various 
movements. 

The  fibres  passing  to  the  skeletal  muscles  are  large,  about  14  /< 
to  19  M  in  diameter,  and  their  axis  cvlinders  represent  the  axons  ot 

24 


370 


PHYSIOLOGY 


large  nerve- cells  in  the  anterior  horn.  In  the  dorsal  region  of  the 
cord  in  man,  from  the  second  dorsal  to  the  second  lumbar  nerve- 
roots,  the  anterior  roots  contain,  besides  these  coarse  fibres,  a  number 
of  fine  fibres  about  1-8  m  to  3-6  yu  in  diameter  (Fig.  164).  These  fine 
fibres  were  shown  by  Gaskell  to  leave  the  nerve  shortly  after  the 
junction  of  the  two  roots,  to  pass  as  a  white  ramus  communicans 
to  the  sympathetic.  Excitation  of  the  white  rami  evokes  various  visceral 
effects,  such  as  dilatation  of  the  pupils,  augmentation  of  the  heart, 

contraction  of  blood-vessels, 
inhibition  of  the  gut,  erection 
of  hairs,  &c.  Gaskell  pointed 
out  that  the  outflow  of  these 
fine  fibres  coincided  with  the 
existence  of  a  prominent  lateral 
horn  in  the  gxey  matter,  and 
suggested  that  cells  of  the 
lateral  horn  might  be  regarded 
as  the  origin  of  the  visceral 
nerve  fibres.  This  suggestion 
has  been  confirmed  by  An- 
derson, who  has  shown  that 
section  of  the  white  rami  com- 
municantes  brings  about  an 
alteration  in  the  cells  of  the 
lateral  horn  as  a  result  of 
retrograde  degeneration. 


.0    O  Q  ^^\ 


lif* 


■SSjI 


vw 


K^'iiO<S, 


Fig.  164.  Section  acro.ss  tlic  .■second  thoracic 
ventral  nerve-root  of  the  dog  (stained  -with 
osmic  acid)  to  show  varying  sizes  of  the  con- 
stituent fibres.     (Gaskell.) 


CENTRAL  PATHS  OF  SPINAL  REFLEXES 
The  impulse  entering  the  cord  is  thus  able  to  affect  immediately 
a  number  of  systems-  of  neurons,  namely,  cells  in  the  anterior  horn, 
in  the  posterior  horn,  in  Clarke's  column,  in  the  substantia  gelatinosa, 
in  the  lateral  column  of  the  same  side  of  the  cord,  and  the  corre- 
sponding groups  of  cells  on  the  opposite  side  of  the  cord  either  directly 
by  crossing  collaterals  or  indirectly  through  cells  which  send  their 
axons  across  the  middle  line.  Through  the  ascending  and  descending 
fibres  of  the  posterior  columns  it  can  also  set  into  action  the  reflex 
mechanisms  of  adjacent  segments  of  the  cord.  In  addition  to  this 
direct  spread  of  afferent  impulse  up  and  down  the  cord  there  is  an 
anatomical  basis  for  a  co-ordination  between  the  gxey  matter  of 
different  levels.  This  co-ordination  is  effected  through  the  inter- 
mediation of  the  internuncial  or  intra-spinal  fibres  which  pass  up 
and  down  the  cord  from  segment  to  segment.  The  course  of  the 
descending  fibres  may  be  studied  by  carrying  out  a  total  transection 
of  the  spinal  cord  at  the  sixth  cervical  vertebra,  and  six  months 


THE  SPINAL  CORD  AS  A  REFLEX  CENTRE 


371 


later,  when  all  the  fibres  degenerating  as  a  result  of  the  section  have 
disappeared,  carr^'ing  out  a  further  transection  or  hemisection  a 
few  segments  below  the  first  transection.  If  the  animal  be  killed 
two  or  three  weeks  after  the  second  operation  it  will  be  found  that  a 
number  of  fibres  in  the  white  matter  are  degenerated  below  the 
second  section  (Fig.  165).  These  fibres  therefore  must  be  derived 
from  cells  of  the  grev  matter  situated  between  the  levels  of  the 
lll.T. 


Fig.  16.5.  Cross-sections  of  spinal  cord  of  a  dog,  showing  the  descending 
nerve-tracts  originating  in  the  first  three  thoracic  segments  (method  of 
'  successive  degeneration ').  The  eighth  cervical  segment  had  been 
excised  and  568  days  later  a  cross-cut  was  made  at  level  of  third  thoracic 
nerve.  The  extent  of  the  lesion  is  shown  in  the  first  figure  (III.  T).  The 
other  sections  show  the  degenerations  as  revealed  three  weeks  later  by 
Marchi's  method.     (Sherbikgtox.) 

first  and  second  sections,  and  they  can  be  traced  down  the  cord 
through  a  large  number  of  segments.  Analogous  methods  may  be 
used  for  tracing  the  course  of  the  ascending  intra-spinal  fibres.  These 
intra-spinal  fibres  occur  in  the  following  situations  : 

(1)  In  the  lateral  columns  immediately  outside  the  grey  matter., 
in  the  bay  between  the  anterior  and  posterior  horns. 

(2)  Close  to  the  grey  matter  in  the  anterior  basis  bundle. 

(3)  In  the  posterior  columns,  united  ^^^th  the  descending  branches 
of  the  entering  posterior  roots  in  the  comma  tract,  and  also  in  the 
immediate  periphery  of  the  cord  and  abutting  on  the  posterior  fissure 
in  the  septo- marginal  tract. 

(4)  Mingled  with  the  fibres  of  the  pyramidal  tract. 


372  PHYSIOLOGY 

All  these  tracts  are  mixed,  i.e.  contain  both  ascending  and  de- 
scending fibres.  As  a  rule,  the  longer  the  course  of  a  fibre  the  more 
peripherally  does  it  lie  in  the  cord.  The  shortest  of  the  fibres  may 
only  unite  segment  to  segment,  while  the  longest  fibres  may  run 
through  the  greater  part  of  the  length  of  the  cord. 

THE  SPINAL  ANIMAL 
An  animal  possessing  only  a  spinal  cord  contains  a  reflex  neural 
apparatus  which  can  be  excited  to  activity  by  impulses  of  various 
qualities  and  from  any  part  of  the  skin.  Thus  the  afferent  impulse 
may  correspond  to  what  in  ourselves  we  call  tactile  and  be  provoked 
by  mechanical  stimulation,  or  may  result  from  changes  of  tempera- 
tiure  and  correspond  to  those  producing  sensations  of  heat  and  cold. 
Strong  stimuli  of  any  kind  may  give  rise  also  to  afferent  impulses  which 
in  the  intact  animal  would  have  the  quality  of  pain.  Since  these 
stimuli  are  such  as  to  produce  injury  if  continued,  they  may  be  named, 
when  applied  to  the  spinal  animal,  pathic  or  nocuous.  The 
spatial  distribution  of  the  stimulus  will  determine  the  situation  and 
number  of  nerve  fibres  set  into  action,  so  that  there  will  be  a  gxeat 
variation  in  the  distribution  of  the  excited  neiurons  of  the  central 
grey  matter  according  to  the  quality,  distribution,  and  intensity  of 
the  stimulus.  The  efferent  part  of  the  reflex  is  provided  for  by 
the  connection  of  the  anterior  cornual  cells  to  the  whole  skeletal 
musculature  of  the  body,  as  well  as  by  the  distribution  of  the  axons 
of  the  lateral  horn-cells  to  the  sympathetic  system  and  through  this 
to  the  viscera.  On  the  other  hand,  if  the  spinal  cord  be  separated  from 
the  medulla  oblongata  and  higher  parts  of  the  brain,  it  is  deprived  of 
all  connection  with  the  most  highly  elaborated  sense-organs  of  smell, 
sight,  hearing,  and  equihbration,and  also  of  the  important  afferent  and 
efferent  impulses  which  pass  between  brain  and  viscera  through 
the  vagus  nerves.  In  studying  the  reaction  of  the  isolated  spinal 
cord  we  are  studying  a  nervous  system  cut  off  from  its  most  complex 
components,  but  at  the  same  time  deprived  of  the  initiation  and 
guidance  which  it  must  normally  be  continually  receiving  from  the 
higher  sense-organs  through  the  brain.  A  study  of  the  spinal  animal 
will  therefore  be  instructive  as  a  study  of  the  mammalian  nervous 
system  in  its  simplest  possible  aspect.  It  will  however,  in  all  cases 
be  the  study  of  an  incomplete  and  maimed  system,  the  incomplete- 
ness increasing  as  we  ascend  the  scale  of  animals  in  our  experimenta- 
tion, owing  to  the  increasing  subordination  of  the  lower  to  the  higher 
centres,  and  of  the  immediate  reflexes  to  the  educated  reactions  of 
the  anterior  part  of  the  brain. 


THE  SPINAL  CORD  AS  A  REFLEX  CENTRE  373 

SPINAL  SHOCK 
If  the  spinal  cord  of  the  frog  be  divided  just  below  the  medulla, 
for  some  minutes  after  the  section  all  four  limbs  are  perfectly  flaccid, 
and  it  is  impossible  to  evoke  any  reaction  by  the  apphcation  of  the 
strongest  stimuli.  If  the  animal  be  left  to  itself  for  half  an  horn- 
there  is  a  gradual  return  of  reflex  tone  ;  the  animal  draws  up  its  legs  and 
assumes  a  position  not  far  removed  from  that  of  the  normal  frog, 
the  head  being  lower  than  under  normal  conditions.  We  may  say 
that  the  phenomena  of  shock  in  the  frog  last  only  a  short  time.  With 
increasing  complexity  of  the  nervous  system  the  phenomena  of 
shock  become  more  lasting,  so  that  among  laboratory  animals  it  is 
in  the  monkey  that  spinal  shock  is  most  apparent.  It  is  interesting 
to  note,  as  pointed  out  by  vSherrington,  that  shock  appears  to  take 
effect  only  in  the  aboral  direction.  Thus,  even  in  the  monkey,  section 
through  the  lower  cervical  region,  though  causing  profound  paralysis 
of  the  lower  limbs  and  part  of  the  trunk,  apparently  has  no  influence 
at  all  on  the  reactions  of  the  nervous  system  above  the  section.  "  The 
animal  immediately  after  the  section  will  contentedly  direct  its  gaze 
to  sights  seen  through  the  window,  or,  if  the  section  have  been  below 
the  brachial  region,  may  amuse  itself  by  catching  flies  on  the  pane. 
This  is  the  more  remarkable  since  the  profound  depression  of  the 
nerve-centres  below  the  point  of  section  extends  also  to  the  blood- 
vessels and  viscera,  so  that  there  is  a  gxeat  fall  of  blood  pressure 
and  diminished  production  with  increased  loss  of  heat.  The  sphincters 
are  flaccid  or  patulous,  the  skeletal  muscles  are  toneless,  and  no 
reaction  is  evoked  by  the  strongest  stimulus  to  the  skin  or  to  a  sensory 
nerve." 

Much  discussion  has  arisen  as  to  the  duration  of  shock.  Goltz 
and  others  imagined  that  the  phenomena  of  shock  may  persist  for 
months  or  even  years.  According  to  Sherrington,  in  the  higher 
animals  the  phenomena  of  shock  are  compUcated  by  the  onset  of 
an  "  isolation  dystrophy  "  which  may  occur  before  the  condition  of 
shock  has  entirely  disappeared.  In  order  therefore  to  examine  the 
capabilities  of  the  isolated  spinal  cord  at  their  best,  a  time  must 
be  chosen  when  the  sum  of  shock  and  isolation  dystrophy  together 
is  at  its  minimum. 

The  occurrence  of  shock  after  complete  transection  of  the  cord 
in  the  cervical  region  cannot  be  ascribed  to  the  fall  of  blood  pressure 
which  ensues  as  a  result  of  the  severance  of  the  efferent  vaso-motor 
tracts  from  the  vaso-motor  centre  in  the  medulla.  The  centres  above 
as  well  as  those  below  the  transection  are  equally  exposed  to  the 
effects  of  the  lowered  blood  pressure,  but  it  is  only  those  below  the 
section  which  show  signs  of  shock.     Nor  can  it  be  regarded  as  operative 


374  PHYSIOLOGY 

shock  due  to  the  severity  of  the  lesion ;  such  an  operative  shock  would 
be  effective  in  either  direction,  and  we  do  not  find  that  the  method 
of  transection,  whether  by  tearing  across  the  cord  or  cutting  it  with 
a  minimum  disturbance,  alters  appreciably  the  amount  of  shock 
displayed  by  the  segment  of  the  cord  situated  below  the  lesion. 
On  the  other  hand,  if  in  a  dog,  which  has  undergone  transection 
of  the  cord  in  the  lower  cervical  region  and  has  been  allowed  sufficient 
time  to  recover  from  the  shock,  a  second  transection  be  carried 
out  two  or  three  segments  below  the  site  of  the  first  operation,  the 
influence  of  the  second  section  is  hardly  noticeable  on  the  lower 
segment  of  the  cord.  Apparently  then  the  Qhiellactor-i»-^termining 
shock-in. all  those  centres  ^tuated  aborally  of  the  lesion  is  the  cutting 
off  of  the  impulses  which  are  continually  streaming  down  from  the 
higher  centres  and  from  the  great  sense-organs  connected  with  the 
anterior  portions  of  the  nervous  system.  With  every  rise  in  the 
animal  scale  the  impressions  received  by  the  special  senses  take  an 
increasing  part  in  the  determining  of  all  the  reactions  of  the  body, 
so  that  we  might  expect  the  effect  of  cutting  off  the  impulses  from 
the  higher  centres  to  be  gxeater,  the  higher  in  the  scale  of  animal 
life  is  the  animal  on  which  the  experiment  is  carried  out. 

The  state  of  profound  shock  produced  in  the  spinal  cord  by  the 
operation  passes  off  gradually.  The  blood  pressure,  which  may  have 
fallen  to  40  or  50  mm.  Hg.,  rises  within  two  or  three  days  to  its  normal 
height,  i.e.  90  to  110  mm.  Hg.  The  sphincter  muscles  of  the  anus 
gradually  recover  their  tone,  and  within  a  short  time  the  reflex  evacua- 
tion of  the  bladder  and  rectum  may  occur  as  in  a  normal  animal.  The 
skeletal  muscles  recover  their  tone  within  a  few  days,  and  after  a 
short  time  co-ordinated  movements  can  be  brought  about  in  the 
trunk  and  limbs  by  appropriate  stimulation  of  sensory  surfaces.  At 
first  the  reactions  thus  produced  are  feeble  and  the  reflex  is  rapidly 
fatigued.  Of  these  reflexes  those  excited  by  nocuous  or  painful 
stimuli  are  the  first  to  make  their  appearance ;  a  little  later  are 
seen  those  due  to  stimuli  affecting  the  tactile  organs  in  the  skin,  or 
the  sense-organs  of  deep  sensibility  situated  round  the  bones  and 
joints  and  excited  by  deep  pressure  or  changes  in  posture  of  the 
limbs. 

In  a  dog  which  has  undergone  complete  cervical  transection  two 
or  three  months  previously,  the  tone  of  the  muscles  is  somewhat 
increased.  Although  the  dog  is  unable  to  walk,  if  it  be  raised  and 
given  a  little  push  forward,  so  as  to  stretch  the  extensor  muscles 
of  its  hind  limbs,  it  may  take  two  or  three  steps  forward  before  its  legs 
collapse.  Although  the  locomotor  apparatus  is  present,  the  nexus 
is  lacking  which  determines  the  regulation  of  these  movements 
through  the  organs  of  static  sense,  so  that  the  spinal  movements  are 


THE  SPINAL  CORD  AS  A  REFLEX  CENTRE 


375 


insufficient  to  maintain  the  animal  in  such  a  position  that  a  line 
drawn  vertically  from  its  centre  of  gravity  shall  fall  between  its 
points  of  support.  On  the  other  hand,  swimming  movements  may 
be  carried  out  regularly.  The  frog  deprived  of  its  brain  can  swim 
like  a  normal  animal,  but  in  consequence  of  the  depression  of  its  head 
tends  to  swim  ever  deeper  in  the  water.  If  a  '  spinal  '  dog  be  held 
up  by  the  fore  limbs,  the  hind  limbs  nearly  always  enter  into  alternat- 
ing movements  of  flexion  and  extension  ('  mark  time  '  movements), 
the  tjvo  limbs  acting  alternately  as  in  normal  progression.  The 
stimuli  in  this  case  seem  to  be  started  by  the  stretching  of  the  skin 

THE   SI.MPLE    REFLEX 


Fig.  166.     A.  The  receptive  field,  whence  the  scratch  reflex  of  the  left 
hind  limb  can  be  evoked. 

B.  Diagram  of  spinal  arcs  involved.  L,  afferent  path  from  left  foot ; 
R,  afferent  path  from  right  foot  ;  Ra,  R/i,  receptive  paths  from  hairs  on 
'scratch  area';  FC,  final  common  pith  (motor  neuron);  ra,  p^,  proprio- 
spinal  neurons.     (Sherrington.) 


and  other  structures  at  the  front  of  the  thighs.     In  such  animals  three 
reflexes,  amongst  others,  can  be  excited  almost  invariably,  viz.  : 

(1)  Scratch  reflex .  Gentle  stinmlation,  mechanical  or  electrical,  of 
any  point  over  a  saddle-shaped  area  on  the  dorsum  behind  the  shoulders 
(Fig.  166)  causes  rhythmic  movements  of  flexion  and  extension 
of  the  hind  limb  of  the  same  side,  the  effect  of  which  would  be  to 
scratch  away  the  irritant  object.  These  movements  are  repeated 
at  the  rate  of  about  four  per  second. 


376 


PHYSIOLOGY 


(2)  Flexor  reflex.  Nocuous  stimuli,  such  as  the  prick  of  a  needle 
applied  to  any  part  of  the  foot,  causes  flexion  of  the  leg  and  thigh, 
often  accompanied  by  extension  of  the  opposite  hind  hmb. 

(3)  Extensor  or  '  stepping '  reflex.  Gentle  pressure  appMed  to 
the  plantar  surface  of  the  hind  foot,  especially  if  the  hmb  is  some- 
what flexed,  causes  a  movement  of  extension  of  the  limb  accom- 
panied sometimes  by  a  flexion  of  the  opposite  hind  limb. 

In  such  an  animal  the  carrying  out  of  the  visceral  reflexes  may 
be  very  efficient.  The  blood  pressure  has  attained  its  normal  height 
and  mav  be  altered  reflexlv  in  very  much  the  same  wav  as  in  a  normal 


200  mm    Hg. 


150  mm.  Hg. 


100  mm.  HS 
b.  p. 


Signal 
Time  in  2" 


Fig.  167.     Blood-pressuie  tracing  from  a  spinal  dog.     The  signal  indicates 
the  time  during  which  the  aiierent  nerve  was  stimulated.      (Shereingtox.) 


animal,  although  the  medullary  vaso-motor  centre  can  no  longer 
be  concerned.  Thus  in  the  diagxam  (Fig.  167)  is  represented  the 
effect  on  the  blood  pressure  of  exciting  the  central  end  of  the  digital 
nerve  in  a  spinal  dog.  The  pressure  rises  from  90  to  208  mm.  Hg. 
—a  pressor  effect  as  great  as  any  which  can  be  obtained  in  an  animal 
still  possessing  all  the  connections  of  the  vascular  system  with  the 
vaso-motor  centre.  The  height  of  the  rise  shows  that  as  regards  the 
influence  on  the  blood  pressure  the  spinal  cord  must  be  acting  as  a 
whole.  No  effect  on  the  blood-vessels  confined  to  the  segment,  or 
segments,  adjacent  to  that  of  the  nerve  stimulated  would  suffice  to 
cause  a  rise  of  more  than  a  few  mm.  Hg. 

The  reflex  apparatus  for  other  visceral  functions  seems  to  be 
equally  perfect.  The  urinary  bladder,  when  sufficient  urine  is  accumu- 
lated, contracts  forcibly,  the  contraction  being  accompanied  by 
relaxation  of  the  sphincter  and  followed  by  rhythmic  contractions 
of  the  urethral  muscles  ;  accumulation  of  faeces  in  the  rectum  leads 
to  their  normal  evacuation.     With  a  little    assistance    impregnation 


THE  SPINAL  CORD  AS  A  REFLEX  CENTRE 


377 


may  be  effected  in  or  by  such  a  maimed  animal,  and  in  the  female 
may  terminate  at  full  term  in  normal  parturition.  Pregnancy  is 
accompanied  by  hypertrophy  of  the  mammary  glands  and  is  followed 
by  secretion  of  milk,  so  that  the  young  may  be  suckled  as  in  a  normal 
animal.  Similar  phenomena  have  been  observed  in  the  human 
subject. 

Such  an  animal  furnishes  us  with  an  opportunity  of  analysing 
the  factors  which  are  involved  in  the  maintenance 
of  muscle  tone,  as  well  as   in  the  carrying  out  of 
the    simplest  reflexes  involving  contractions  of  the 
skeletal  nmscles. 

MUSCULAR  TONE 

Every  nmscle  in  the  body  is  in  a  condition  of 
slightly  continued  contraction  which  keeps  it  tense, 
so  that  when  it  contracts  in  response  to  a  stimulus 
there  is,  so  to  speak,  no  '  slack  '  to  be  taken  up 
before  the  muscle  begins  to  pull  on  its  attachments. 
This  tone  is  seen  in  the  retraction  imdergone  by 
muscles  or  tendons  when  they  are  divided  in  the 
living  animal. 

If  a  frog  possessing  only  spinal  cord  be  hung 
up  by  its  jaw,  the  hmbs  will  be  observed  to  occupy 
a  position  which  is  short  of  complete  extension. 
The  tone  of  the  muscles  which  is  concerned  in  the 
maintenance  of  this  attitude  is  at  once  abolished 
by  the  destruction  of  the  cord.  It  may  be  abolished 
on  one  side  by  section  either  of  the  anterior  roots 
going  to  the  muscles,  or  of  the  posterior  roots 
coming  from  the  muscles  (Fig.  168).  In  the  intact 
animal  muscle  tone  is  diminished  by  disease  and 
may  be  abohshed  by  any  condition  of  profound 
anaesthesia,  as  it  is  indeed  in  the  condition  of  shock. 

Much  light  has  been  thrown  on  the  factors 
which  determine  muscular  tone  by  a  study 
of  the  '  tendon  phenomena '  of  which  the 
knee-jerk  is  the  most  familiar  example.  If  the  leg  is  allowed 
to  hang  loosely  in  a  position  of  slight  flexion  at  hip  and  knee  and 
the  patellar  tendon  be  struck,  the  extensor  muscles  of  the  thigh 
contract  and  raise  the  leg.  This  phenomenon  is  known  as  the  knee- 
jerk.  Similar  '  tendon  reflexes '  can  be  obtained  in  other  muscles, 
such  as  the  tendo  Achillis,  the  triceps,  and  the  extensor  muscles 
of  the  wrist,  but  with  not  so  great  ease  as  is  the  case  with  the  knee. 
The  knee-jerk  is  not  altered  by  rendering  the  tendon  anaesthetic  by 


Fig.  168.  Hind  part 
of  a  spinal  frog, 
hung  up  by  the 
jaw.  The  x>osterior 
roots  of  the  nerves 
to  the  left  hind 
limb  have  been 
divided. 

(Bechtekew.) 


378  PHYSIOLOGY 

section  of  all  its  nerves.  The  essential  feature  is  a  slight  passive 
increase  of  the  tension  to  which  the  muscle  is  already  subjected. 
Since  the  jerk  is  abolished  by  severance  at  any  point  of  the  reflex 
arc,,  viz.  mviscle  spindle,  cord,  muscle,  it  was  thouglit  at  first  to  be 
of  the  nature  of  a  reflex  action.  The  interval,  however,  which  elapses 
between  the  moment  at  which  the  tendon  is  struck  and  the  response 
of  the  muscle  is  generally  considered  to  be  too  short  to  allow  of  an 
impulse  to  travel  from  the  tendon,  or  muscle,  up  to  the  cord  and 
back  again  to  the  muscle.  The  interval  was  found  by  Gotch  to  be 
about  -005  sec,  whereas  the  latent  period  of  contraction  which 
ensues  upon  direct  stimulation  of  the  vastus  internus  is  also  -005 
.sec.  On  the  other  hand,  the  latent  period  when  the  nerve 
to  the  muscle  was  stimulated  was  -01  sec.  The  lost  time  of  the 
knee-jerk  is  less  than  one-quarter  of  that  of  the  briefest  reflex  time. 
The  contraction  must  therefore  be  due  to  the  direct  stimulation  of 
the  muscle  by  the  sudden  stretching  produced  on  striking  its  tendon. 
Mere  tension  of  the  muscle  i&imt,  however,  the  only  factor.  The  tone 
which  is  reflexly  maintained  in  the  muscle  is  necessary  for  this  response 
to  direct  stimulation  to  take  place,  and  it  seems  to  keep  the  nmscles 
in  a  state  of  wakefulness  ready  to  respond  to  the  slightest  local 
.stimyjation.  The  knee-jerk  is  therefore  of  special  importance  as 
an  index  to  the  tonic  condition  of  the  muscles  concerned,  being  brisk 
and  easily  elicited  when  the  tonus  is  pronounced,  and  slight  or  absent 
when  the  tone  of  the  muscle  is  depressed. 

Especially  interesting  is  the  relation  shown  by  Sherrington  to 
exist  between  the  tonic  condition  of  antagonistic  muscles,  e.g.  between 
the  hamstrings  and  the  vastus  internus  of  the  quadriceps  extensor 
muscle.  Section  of  the  hamstring  muscles  (so  as  to  relax  them) 
or  even  section  of  their  nerve  causes  at  once  great  increase  in  the 
jerk  elicited  by  tapping  the  patellar  tendon.  On  the  other  hand, 
the  knee-jerk  is  abolished  by  stretching  the  hamstring  muscles,  or 
by  weak  stimulation  of  the  central  end  of  the  cut  nerve  to  the  ham- 
strings (Fig.  169). 

In  this  way  a  voluntary  flexion  of  the  knee  by  contraction  of 
the  hamstrings  automatically  abolishes  the  resistance  which  would 
be  offered  by  the  tonic  contraction  of  the  extensor  muscles.  In  the 
absence  of  such  an  arrangement  every  movement  of  a  joint,  by 
stretching  the  antagonistic  muscles,  would  automatically  increase 
their  tone,  and  thus  set  up  a  resistance  to  itself.  The  subject  would 
thus  be  muscle-bound. 

Very  great  exaggeration  of  the  tendon  phenomenon  is  observed 
in  cases  where  the  pyramidal  tracts  are  degenerated,  and  indicates 
a  heightened  reflex  excitability  of  the  lower  spinal  centres,  perhaps 
reinforced   by   impulses   from   the   cerebellum.     The    importance   of 


THE  SPINAL  CORD  AS  A  REFLEX  CENTRE 


379 


the  latter  impulses  in  determining  the  myotatic  irritability  of  the 
muscles  is  especially  marked  in  man,  where  total  transverse  lesion 
of  the  upper  part  of  the  spinal  cord  often  abolishes  permanently 
the  tone  of  the  muscles  innervated  from  the  lower  portion  of  the 
cord,  and  especially  the  knee-jerk.  How  far  this  absence  of  tone 
is  due  to  collateral  changes  in  the  cord  has  not  yet  been  determined. 
In  animals  complete  transverse  section  of  the  cord  of  the  cervical 
region  is  followed  by  increase  of  the  knee-jerk,  which  in  the  rabbit  may 
be  elicited  within  a  quarter  of  an  hour  after  the  section  has  been  carried 


L.3 


L.4 


Fio.  169.     Diagram  to  show  muscles  and  nerves  concerned  in  Sherrington's 
experiment  on  the  reciprocal  innervation  of  antagonistic  muscles. 
I..3,  1.4,  l5,  third,  fourth,  and  fifth  lumbar  roots  ;  si,  s2,  first  and  second 
sacral  roots. 


out.     In  the  increased  myotatic  irritability  observed  after  removal 

of  the  cerebral  cortex,  or  after  degeneration  of  the  pyramidal  tracts 

coming  from  the  motor  cortex,  a  single  tap  on  the  patellar  tendon 

may  evoke  a  series  of  contractions  of  the  extensor  muscles  of  the 

thigh,  giving  rise  to  what  is  known  as  knee  chnus.     In  the  same  way 

forcible  flexion  of  the  ankle  causes  a  series  of  rhythmic  contractions 

of  the  calf  muscles  (ankle  clonus),  varying  in  rh}^:hm  from  six  to 

ten  per  second.     The  heightened  tone  of  the  muscles  under  these 

conditions,  and  the   ease    with  which   any  slight  increase  in   theh' 

tension  gives  rise  to  clonic  contractions,  cause  such  patients  to  have 

a  peculiar  dancing  gait,  characteristic  of  pyramidal  degeneration, 

and  known  as  the  '  spastic '  gait  ;    it  is  generally  associated  with  a 

certain  loss  of  voluntary  control  of  the  movements  of  the  limbs,  so 

that  the  whole  complex  of  symptoms  is  called  '  spastic  paraplegia.' 


380  PHYSIOLOGY 

Tiie  value  of  the  tendon  phenomena  as  a  means  of  diagnosis  has 
tended  to  obscure  their  great  importance  in  the  normal  individual. 
Every  joint  is  protected  by  inextensible  ligaments  and  by  muscles. 
A  sudden  strain  on  a  ligament  either  will  have  no  effect,  or  will 
rupture  some  of  its  fibres  and  perhaps  injure  the  adjacent  joint 
surfaces.  An  ordinary  reflex  contraction  would  be  powerless  to 
prevent  this,  since  the  mischief  would  be  done  before  the  reaction 
could  take  place.  But  the  central  nervous  system  confines  itself  to 
keeping  the  muscles  awake,  so  that  they  themselves  may  react  to 
any  sudden  increase  in  their  tension  by  an  equally  sudden  contrac- 
tion, which  saves  the  joint  before  the  central  nervous  system  has 
even  become  aware  of  the  strain. 

The  tone  of  the  muscles,  as  well  as  the  consequent  tendon  pheno- 
mena, is  dependent  on  the  integrity  of  the  reflex  arc  governing  the 
muscles  in  question.  It  has  been  shown  by  Sherrington  that  the 
afferent  part  of  the  arc  is  represented  by  the  afferent  nerves  from 
the  muscle  itself,  and  that  these  nerves  receive  their  sense  impressions 
from  the  special  nerve-endings  characteristic  of  muscle^ — the  '  muscle- 
spindles.'  Even  in  the  purely  muscular  nerves  a  large  proportion 
of  the  fibres  are  afferent  in  function,  and,  after  section  of  the  appro- 
priate posterior  roots  distal  to  the  ganglia,  as  many  as  40  per  cent, 
of  the  fibres  going  to  a  muscle  may  be  found  degenerated.  Though 
most  of  these  have  the  muscle-spindles  as  their  destination,  a  certain 
number  pass  to  the  tendon  and  aponeuroses  connected  with  the 
muscle,  where  they  end  in  the  end  organs  known  as  the  organs  of 
Golgi  and  the  organs  of  Kufiini.  After  section  of  the  motor  nerves 
the  muscle  fibres  degenerate,  with  the  exception  of  the  modified 
fibres,  which,  enclosed  in  a  connected  tissue  sheath,  are  concerned 
in  the  formation  of  the  muscle-spindles.  Muscle  tone  and  tendon 
phenomena  may  therefore  be  abolished  by  lesions  of  afferent  nerves, 
wliich  leave  a  considerable  part  of  the  cutaneous  sensibility  of  the 
limb  intact.  In  man  the  spinal  reflex  mechanism  connected  with 
the  knee-jerk  is  situated  in  the  third  and  fourth  lumbar  segments. 
The  jerk  may  be  abolished  by  section  of  the  third  and  fourth  posterior 
nerve-roots,  although  to  render  the  whole  hind  limb  ana3sthetic  it 
would  be  necessary  to  divide  all  the  roots  from  the  second  lumbar  to 
the  fourth  sacral  inclusive. 

Recent  researches  by  Snyder  and  by  Jolly  indicate  that  the  reflex 
nature  of  the  knee-jerk  cannot  be  entirely  excluded.  Jolly,  using  the  string 
galvanometer,  has  taken  the  current  of  action  in  the  vastus  intemus  muscle 
as  an  index  of  the  commencing  contraction  of  this  muscle  in  the  knee-jerk. 
He  has  also  by  the  same  method,  by  leading  oflf  the  aflEerent  and  efferent  nerves 
respectively,  measured  the  lost  time  in  the  sense-organs  and  in  the  motor  end- 
plates  of  the  muscle.  In  the  spinal  cord  he  obtained  the  following  electrical 
latencies  in  one  case: 


THE  SPINAL  CORD  AS  A  REFLEX  CENTRE  .^81 

Latency  of  knee-jerk  .....  5-3(r* 

Afferent  endings  .....      0-4a 

Nerve  conduction  .  .  .  .  .1-4 

Motor  endings  and  action  current  .  .1-3 

31 

Synapse  time  ....  2-2o- 

In  this  case  the  shortest  latency  determined  for  nerve-endings  has  been 
deducted  from  the  shortest  latent  period  obtained  from  the  knee-jerk  in  the 
spinal  cat.  On  the  other  hand,  some  decapitated  preparations  have  been 
found  to  present  considerably  longer  latent  periods,  e.g.  11  and  12o-.  This 
variation  in  the  latent  period  supports  the  view  that  the  knee-jerk  is  a  reflex 
of  which  the  synapse  time  is  very  short,  about  2o-,  and  that  in  certain  cases 
there  may  be  increased  delay  in  the  spinal  cord.  When  the  latencies  of  the 
knee-jerk  and  the  homonymous  flexor  reflex  are  compared  by  the  electrical 
motliod,  it  is  found  that  the  latter  is  roughly  double  the  former,  the  average 
latency  of  the  knee-jerk  in  the  spinal  cat  being  Q-6a,  and  of  the  homonymous 
flexor  reflex  13-2o-.  Jolly  suggests  that  this  difference  may  be  due  to  the  fact  that 
the  knee-jerk  mechanism  involves  only  one  spinal  synapse  or  set  of  synapses, 
while  the  flexor  reflex  may  involve  two..  In  these  estimates  the  rate  of 
conduction  in  mammalian  nerve  has  been  taken  at  120  metres  per  second. 

*     cr  =  -001  sec. 


SECTION  VIII 

THE  MECHANISM  OF  CO-ORDINATED 
MOVEMENTS 

The  detailed  study  of  the  chief  reflexes  obtainable  from  a  spinal 
animal  has,  in  Sherrington's  hands,  yielded  much  information  as 
to  the  linking  of  the  various  events  which  are  concerned  in  the  carrying 
out  of  every  co-ordinated  movement,  and  as  to  the  conditions 
which  determine  the  sequence  and  extent  of  the  activities  involved. 
We  may  take,  as  the  type  of  such  a  reflex,  the  flexion  of  the  leg 
and  thigh  which  ensues  on  the  application  of  a  painful  stimulus 
to  the  ball  of  the  foot,  such  as  pricking  with  a  needle,  or  the  applica- 
tion of  the  faradic  current.  Of  course,  in  the  spinal  animal  no  pain 
can  result  from  stimulation  of  any  part  below  the  level  of  section  of 
the  cord,  and  it  is  better  therefore  under  such  circumstances  to 
speak  of  nocuous  or  pathic  stimuli,  since  all  stimuli  which  cause 
pain  are  such  that,  if  their  operation  continued,  they  would  result 
in  damage  to  the  material  structure  of  the  animal.  This  flexor 
reflex  is  also  easily  obtainable  in  the  frog  as  a  result  of  stimulating 
one  of  its  toes  by  mechanical  or  chemical  stimuli,  but  it  is  easier 
to  analyse  the  different  events  involved  in  the  reaction  in  the  case 
of  the  larger  animal. 

The  effect  varies  with  the  strength  of  the  stimulus.  The  minimal 
effective  stimulus  causes  simply  movement  of  the  foot.  As  its 
strength  is  increased  this  movement  is  attended  by  flexion  of  the  leg  on 
the  thigh,  and  finally  by  flexion  of  the  thigh  on  the  body.  With 
still  further  increase  there  is  a  spread  to  the  opposite  hind  limb, 
which,  however,  performs  the  opposite  movement  of  extension. 
Increase  in  the  strength  of  stimulus  causes  not  only  an  increase  in 
the  strength  of  contraction  of  the  reacting  nmscles  but  also  an 
extension  of  the  reaction  to  more  and  more  muscles,  or  groups 
of  muscles.  The  spread  occurs  always  in  definite  order.  The 
stimulus  when  represented  by  the  prick  of  a  needle  can  affect  only 
one  or  two  nerve  fibres.  The  impulse  carried  along  these  fibres 
through  a  posterior  root  to  the  cord  spreads  in  the  cord,  affects  the 
motor  neurons  of  the  anterior  horns,  and  causes  these  to  dis- 
charge.    The  first   discharge   is   as   a  rule   limited  to  those  in   the 

immediate    proximitv    of    the    entering    impulses,    but    even    when 

382 


THE  MECHANISM  OF  CO-ORDINATED  MOVEMENTS    383 

minimal,  involves  the  simultaneous  action  of  more  than  one  anterior 
root.  We  may  say  that  the  motor  response  is  determined  to  a  certain 
extent  by  the  spatial  proximity  of  the  afferent  to  the  efferent  tracts, 
but  that  it  is  always  pluri-segmental,  the  most  important  deter- 
mining factor  being  the  adaptation  of  the  movement  to  the  stimulus 
which  is  applied. 

The  gradual  spread  of  the  response  with  increasing  strength  of 
stimulus  is  spoken  of  as  '  irradiation'  The  nature  of  the  response 
is  determined  by  the  locus  or  place  of  application  of  the  stimulus 
and  by  the  quality  of  the  latter.  While  a  painful  stimulus  causes 
flexion  of  the  leg,  deep  pressure  on  the  plantar  surface  of  the  paw 
causes  extension — the  '  stepping '  reflex.  However  extensive  the 
irradiation,  the  muscles  which  are  set  into  action  are  always  such 
that  their  actions  co-operate  towards  a  given  end.  Thus,  when  the 
impulse  spreads  to  the  opposite  hnib  and  produces  an  extension,  the , 
reaction  is  such  as  would  ensue  when  the  dog  steps  on  a  sharp  point 
and  immediately  retracts  the  irritated  limb  away  from  the  injurious 
agent  while  it  extends  the  other  limb  in  the  first  act  of  progression 
or  movement  away  from  the  dangerous  spot. 

A  superficial  study  of  this  reflex  would  therefore  lead  us  to  the 
conclusion  that,  by  the  varying  resistance  in  the  different  synapses 
on  the  course  of  the  connections  of  the  stimulated  afferent  nerves, 
the  impulses  are  directed  so  as  to  affect  solely  and  exclusively  the 
muscles  whose  activity  will  co-operate  and  aid  the  primary  reflex. 
Such  a  description  would,  however,  only  represent  one  half  of  the 
process.  Every  muscle  in  the  body  is  in  a  state  of  tone  var\nng 
with  its  extension.  If  this  tone  is  not  to  inteiiere  with  the  carrying 
out  of  a  reflex  movement,  there  must  be  some  men.ns  by  which  it  can 
be  inhibited.  Such  an  inhibition  we  have  seen  occur  as  the  result 
of  contraction  of  antagonistic  muscles ;  but  the  remarkable  fact 
has  been  brought  out  by  Sherrington  that  the  impulses,  which  start 
on  the  surface  of  the  body  and  set  loose  a  chain  of  motor  impulses 
resulting  in  the  co-ordinated  contraction  of  certain  muscles,  spread 
at  the  same  time  to  the'  motor  mechanisms  governing  the  muscles 
antagonistic  to  the  movement,  and  exercise  on  these  an  inhibitory 
effect. 

This  inhibition  can  be  easily  shown  in  a  spinal  animal  in  the 
following  way.  The  anterior  thigh  muscles  are  cut  away  from  their 
attachments  to  the  tibia  and  the  patellar  tendon  connected  by  a 
thread  with  a  recording  lever.  On  then  exciting  the  flexor  reflex 
by  nocuous  stimulation  of  the  foot,  the  lever  attached  to  the  patellar 
tendon  falls  (Fig.  170b).  showing  that  the  extensor  muscles  have 
undergone  actual  elongation.  The  same  effect  is  observed  even 
when  the  hamstrings,  the  flexors  of  the  knee,  have  been  divided.     The 


384  PHYSIOLOGY 

inhibition  of  the  flexor  tone  is  thus  not  determined  by  the  increased 
tension  of  the  flexors,  but  is  a  direct  result  of  the  primary  cutaneous 
stimulus. 


Fig.  170,  a  and  b.  (Sherrington.) 
The  flexion  reflex  observed  as  reflex  contraction  (excitation)  of  the  flexor 
muscles  of  the  knee  (a),  and  as  reflex  relaxation  (inhibition)  of  the  extensor 
muscle  (b).  The  stimulus  was  a  series  of  weak  break  induction  shocks 
applied  to  a  twig  of  the  internal  saphenous  nerve  below  the  knee.  Observa- 
tion B  was  made  four  minutes  after  a.  Note  the  summation  of  stimuli,  in 
each  case  six  stimuli  being  required  before  the  reaction  was  evoked. 


From  a  broad  standpoint  the  function  of  the  nervous  system  is 
the  co-ordination  of  all  the  activities  of  the  body,  so  that  these  may 
be  combined  to  one  common  end,  viz.  the  preservation  of  the  organism. 
For  this  purpose  there  must  be  no  clashing  between  opposing  activities 
of  different  parts.     If  one  part  is  engaged  in  any  action  this  action 


THE  MECHANISM  OF  CO-ORDINATED  MOVEMENTS     385 

must  be  tlie  policy  of  the  body  as  a  whole.  Yet  the  surface  of  the 
body  is  being  continually  played  upon  by  ever-changing  stimuli, 
tending  to  excite  first  one  reflex  and  then  another,  and  the  activities 
so  excited  would  produce  confusion  in  the  conduct  of  the  animal,  if 
there  were  not  some  means  by  which  at  any  one  time  only  one  reaction 
should  be  in  the  act  of  being  carried  out.  The  imperative  stimulus 
should  dominate  the  actions  of  the 
body  as  a  whole.  Just  as,  in  the 
mental  world,  attention  must  be  un- 
divided if  we  are  to  avoid  confusi(jn 
of  judgment,  so  in  the  lower  nervous 
activities  there  must  always  be  con- 
centration on  one  act  or  another. 
There  may  be  a  struggle  of  different 
stimuli,  but  one  must  finally  be  pre- 
potent and  annul  altogether  the  in- 
fluence of  the  others.  The  study  of 
the  spinal  animal  shows  that  this 
concentration  of  energy  is  obtained  by 
the  process  of  inhibition.  Every  suc- 
cessful reflex,  i.e.  one  which  actually 
occurs,  inhibits  all  other  reflexes  which 
are  not  co-operative  with  the  one 
which  is  taking  place.  We  may,  for 
instance,  stimulate  the  area  of  skin 
which  gives  rise  to  the  scratch  reflex, 
and  at  the  same  time  apply  a  painful 
stimulus  to  the  foot.  The  result  is  not 
a  movement  compounded  of  the  two 
reflexes,  but,  as  a  rule,  the  flexor 
reflex  preponderates.  If,  for  instance, 
the  scratch  reflex  be  proceeding  and 
then  the  foot  be  pricked,  the  scratch 
reflex  immediately  comes  to  an  end, 
and  the  flexor  reflex  occurs.  When 
this  in  its  turn  has  come  to  an  end.  the  scratch  reflex  may  be  once 
more  resumed  (Fig.  171). 

One  stinmlus  may  reinforce  another  if  the  reactions  ensuing  on  the 
two  stimuli  are  allied — i.e.  tend  to  co-operate  one  with  another.  In 
every  other  case,  however,  an  afferent  impulse  entering  the  cord  and 
spreading  to  a  motor  mechanism,  so  as  to  produce  a  co-ordinate  con- 
traction of  various  muscles,  causes  at  the  same  time  inhibition  of  the 
muscles  antagonistic  to  the  movement,  and  a  block,  or  inliibition.  in 
all  other  reflex  arcs  of  the  cord. 

25 


Fio.    171.     Scratch  icficx  tempo- 
rarily inhibited  by  applicatiou 
of  a  j)athic  stimulus  to  foot. 
Signal  A,  stimulation  of  scratch 
area.    Signal  B,  stimulation  of  paw 
bv  strong  induction  shock. 


386 


PHYSIOLOGY 


The  anatomical  basis  of  the  various  events  involved  in  the  carrying 
out  of  such  a  reflex  as  that  just  studied  is  shown  in  the  diagram  (Fig. 
172).  In  this  diagram  the  nerve-fibre  a  represents  the  pain-receiving 
or  nociceptive  nerve  from  the  skin  of  the  foot.  This  passes  by  a 
posterior  root  into  the  spinal  cord,  where  it  divides  and  gives  off  a 
number  of  collaterals.  These  collaterals,  as  we  have  already  seen, 
pass  in  various  directions  ;  some  to  the  neighbouring  grey  matter,  some 
to  the  centres  in  the  higher  parts  of  the  nervous  system.     Neglecting 


Fig.  172.  Diagram  indicating  connections  and  actions  of  two  afferent  spinal 
root-cells  a  and  a',  in  regard  to  their  reflex  influence  on  the  extensor  and 
flexor  muscles  of  the  two  knees.  The  sign  +  indicates  an  excitatory 
effect,  the  sign  —  an  inhibitory  effect.     (Sherrington.) 

the  latter  and  any  intermediate  neuron  which  may  be  intercalated 
between  the  afferent  fibre  and  the  motor  cell,  we  see  that  those  col- 
laterals which  affect  the  motor  cells  of  the  muscles  of  the  two  hind 
limbs  can  be  divided  into  two  sets,  one  of  which  always  produces 
during  activity  excitation  in  certain  efferent  neurons,  whilst  the 
other  produces  inhibition  of  the  efferent  neurons  of  the  antagonistic 
muscles.  The  single  afferent  nerve  fibre  is  therefore,  with  regard  to 
one  set  of  its  central  terminal  branches,  specifically  excitor,  and,  in 
regard  to  another  set  of  its  central  endings,  specifically  inhibitor.  In 
the  case  in  point  the  central  terminal  branches  of  the  nerve  a  are 


THE  MECHANISM  OF  CO-ORDINATED  MOVEMENTS     387 

excitor  for  the  flexor  muscles  of  the  same  side  and  for  the  extensor 
muscles  of  the  opposite  side,  and  inhibitor  for  the  extensor  muscles  of 
the  same  side  and  for  the  flexor  muscles  of  the  opposite  side. 

The  ascending  branches  of  the  nerve  fibre  in  the  same  way  will 
have  endings  which,  while  inhibitor  for  the  greater  number  of  other 
possible  reflex  changes,  will  be  excitor  in  a  slight  degree  for  certain 
efferent  neurons  whcse  action  is  allied  to  that  of  the  primary  reflex. 
The  diagram  shows  also  that  the  contraction  of  the  flexor  muscle, 
set  up  as  the  result  of  stimulating  a,  itself  initiates  a  secondary  reflex 
process  from  muscle  up  the  nerve  fibre  a  and  back  again  to  the  muscle 
by  the  efferent  neuron.  This  muscular  afferent  nerve  also  has  central 
terminations  of  two  signs — excitor  to  itself  and  inhibitor  to  the 
antagonistic  muscles.  For  the  sake  of  clearness  the  diagram  omits 
a  number  of  other  channels  coming  from  other  regions  of  the  cord,  or 
from  other  afferent  nerves,  the  sign  of  which  would  be  negative,  i.e. 
which  would  tend  to  inhibit  the  activity  of  the  whole  reflex  arc. 

We  see  therefore  that  from  every  sensitive  pointy  on  the  surface  of 
the  body  impulses  can  be  initiated  which  will  set  into  action  whole 
chains  of  neurons,  and  will  have  a  widespread  influence  throughout 
the  central  nervous  system.  It  is  important  to  note  that  the  efferent 
path  innervating,  say,  the  flexor  muscles  of  one  side  is  common  to 
many  reflexes.  It  is  used,  for  instance,  by  mutually  antagonistic 
reflexes  such  as  the  scratch  reflex  and  the  flexor  or  pain  reflex.  We 
must  assume  therefore  that  the  mutual  inhibition  of  different  reflexes 
occurs,  not  in  the  •  final  common  path ' — i.e.  in  the  motor  neurons, 
which  must  always  remain  open — but  further  back  in  the  arc,  probably 
near  its  afferent  side. 

We  have  reason  to  believe  that  the  propagation  of  impulses 
through  the  central  nervous  system  involves  expenditure  of  energy, 
and  that  the  seat  of  this  expenditure  may  be  located  in  all  probability 
at  the  synapses.  It  follows  that  the  result  of  any  particular  sensory 
stimulation  will  not  be  absolutely  invariable,  but  that  the  spread  of 
the  nerve  process  in  the  nervous  system,  and  the  degree  of  block  pre- 
sented by  the  various  synapses  and  determining  the  potency  of  any 
given  reaction,  will  depend  on  the  condition  of  the  various  synapses 
at  the  time  of  the  stimulation. 

This  condition  may  be  altered  in  various  ways.  Repeated  excita- 
tion causes  in  the  synapses,  just  as  in  the  nerve-endings  of  the  skeletal 
muscle,  a  condition  of  fatigue.  Stimulation  confined  to  a  single  point 
in  the  '  scratch  area  '  of  the  spinal  dog  excites  a  scratch  reflex  which 
rapidly  dies  away.  On  shifting  the  exciting  electrodes  a  little  to  one 
side  the  reflex  act  begins  again,  often  with  greater  force  than  at  first, 
and  a  very  prolonged  reaction  can  be  induced  by  gradually  moving  the 
electrodes  along  the  surface  of  the  skin.     A  reflex  arc  therefore  rapidly 


388 


PHYSIOLOGY 


shows  signs  of  fatigue,  and  the  minute  change  in  locus  of  stimulus 
which  is  required  to  reinduce  a  practically  identical  action  shows  that 
the  seat  of  fatigue  must  lie  chiefly  on  the  afferent  side  of  the  arc  ; 
perhaps  in  the  first  synapses  through  which  the  impulse  has  to  pass. 
This  easy  incidence  of  fatigue  tends  to  cut  short  any  given  reaction 
and  to  render  it  easier  for  other  reactions  to  take  its  place. 

Just  as  excitation  causes  fatigue  and  therefore  furnishes  a  hin- 
drance to  repetition  of  the  same  act,  so  the  reverse  process  of  inhibition, 
which  is  a  large  component  of  every  reaction,  is  followed  by  a  condi- 
tion of  increased  excitability,  or  diminished  resistance  to  the  passage 
of  impulses.     In  each  case  there  is  a  tendency  for  a  '  swing-back  '  to 


Fig.  173.  '  Mark-time  '  reflux  in  spinal  dog,  inhibited  by  slight  stimulatiun 
of  the  tail  (duration  of  stimulation  shown  by  signal).  Note  the  augmenta- 
tion of  the  mark-time  reflex  following  the  inhibition  {successive  spinal 
induction).     (Sherrington.  ) 

take  place  from  inexcitability  to  over-excitability,  from  excitation  to 
inexcitability.  This  '  successive  spinal  induction,'  as  it  has  been 
termed,  may  be  seen  on  inhibiting  some  movement  by  the  excitation  of 
an  independent  reflex.  Thus  the  scratch  reflex  is  excited,  and  then 
while  the  excitation  is  still  continued  the  reaction  is  inhibited  by 
excitation  of  the  extensor  or  stepping  reflex.  As  soon  as  the  '  step- 
ping '  reflex  has  passed  off,  the  scratch  reflex  returns  with  an  intensity 
greater  than  before.  This  successive  spinal  induction  explains  the 
tendency  which  exists  in  the  spinal  cord  to  an  alternation  of  response  ; 
every  act  tending  to  come  to  an  end  by  fatigue  and,  as  a  result  of 
negative  spinal  induction,  inducing  the  opposed  or  antagonistic  act. 
Thus  if  a  spinal  dog  be  held  up  in  the  vertical  position,  so  that  the 


THE  MECHANISM  OF  CO-ORDINATED  MOVEMENTS     389 

hind  limbs  hang  freely,  these  latter  execute  a  series  of  alternate  move- 
ments of  flexion  and  extension.  The  starting-point  of  these  is  the 
stretching  of  the  anterior  thigh  muscles.  Once  started  they  continue 
of  themselves,  each  act  exciting  the  alternating  antagonistic  act. 

A  reflex  act  has  often  been  distinguished  from  other  reactions, 
described  as  conscious  or  purposive,  by  its  fatality — i.e.  by  the 
invariability  with  which  it  results  on  a  given  stimulus,  whether  the 
reaction  be  for  the  good  of  the  animal  as  a  whole  or  not.  Thus  a 
decapitated  eel  will  wind  itself  with  equal  readiness  around  a  stick  or  a 
hot  poker.  All  reactions  are,  however,  purposive.  The  machinery  for 
them  has  been  evolved  and  the  paths  laid  down  in  the  spinal  cord  under 
the  action  of  natural  selection,  so  that  they  must  act,  at  any  rate  in  the 
average  of  cases,  towards  the  well-being  of  the  animal  as  a  whole. 
Since  the  nerve  path  involved  in  any  reaction  includes  a  number  of 
synapses,  each  of  which  may  be  influenced  from  other  parts  of  the 
body  in  a  positive  or  negative  direction,  an  absolute  uniformity  of 
response  cannot  be  predicated  for  any  one  reaction.  There  wuU  be 
changes  in  the  facility  with  which  it  is  evoked  and  changes  in  its 
extent,  and  these  will  become  the  more  operative  the  greater  the 
complexity  of  the  arc,  and  the  larger  the  number  of  other  impulses 
to  which  it  may  be  subject.  The  fatality  of  response  is  therefore  only 
shown  at  its  best  in  the  very  simplest  of  reflexes,  or  the  most  lowly 
organised  nervous  systems. 

The  purposive  character  of  the  reflexes  obtained  from  the  spinal  frog  has 
sometimes  led  WTiters,  especially  in  pre -Darwinian  days,  to  endow  the  spinal 
cord  with  a  guiding  intelligence.  At  the  present  time  we  recognise  that  every 
reaction  of  a  living  being  must  be  purposive,  in  the  sense  of  being  adapted  to 
the  preservation  of  the  species,  if  the  latter  is  to  survive  in  the  struggle  for 
existence.  The  question  as  to  whether  we  are  justified  in  predicating  the 
existence  of  even  a  germ  of  consciousness  or  volition  in  the  spinal  animal  must 
be  decided  in  the  negative.  "  Associative  memory  would  seem  to  be  a  postulate 
for  the  very  existence  of  perception.  Where  even  simplest  ideas  are  not,  there 
cannot  be  consciousness.  Animal  movements  that  are  appropriate  not  only 
for  an  immediate  but  also  for  a  remote  end  indicate  associative  memory.  Tlie 
approach  of  a  dog  in  answer  to  the  calling  of  its  name,  the  return  of  an  animal 
when  hungry  to  the  place  where  it  has  been  wont  to  receive  food,  such  move- 
ments may  be  taken  as  indicative  of  consciousness  since  they  indicate  the 
working  of  associative  memory.  Examined  by  this  criterion  all  purely  spinal 
reactions  fail  to  evince  fcatiu-es  of  consciousness  "  (Sherrington). 

THE  PART  PLAYED  BY  AFFERENT  IMPRESSIONS  IN  THE  CO- 
ORDINATION OF  MUSCULAR  MOVEMENTS.  Every  reflex  act  is 
initiated  in  the  tirst  place  by  some  form  of  sensory  stimulus.  In  the 
carrying  out  of  the  nuiscular  contractions  and  the  resultant  movements 
of  the  limbs,  other  impulses  are  set  up  in  the  structures  which  subserve 
deep  sensibility,  including  those  of  muscles,  which  in  their  turn  affect 
the    excitability   and   the   activity   of   the   motor   neurons.       These 


390  PHYSIOLOGY 

secondary  afferent  impulses  are  important  whether  the  movements  be 
aroused  by  immediate  sensory  stimulation  of  the  surface  of  the  body, 
or  through  the  higher  parts  of  the  brain,  as  in  volitional  movements. 

Their  significance  is  shown  by  the  marked  disorders  of  movement 
produced  in  a  limb  by  section  of  some  or  all  of  its  afferent  nerves. 
Thus  if  all  the  posterior  roots  supplying  one  hind  limb  of  the  frog  be 
divided  the  posture  of  the  desensitised  limb  is  abnormal,  whether  the 
frog  be  suspended  or  be  in  a  sitting  posture.  Such  a  frog  generally 
swims  with  the  desensitised  limb  in  permanent  active  extension. 
The  complete  absence  of  muscular  tone  under  these  circumstances 
has  already  been  mentioned.  When  a  contraction  of  the  quadriceps 
extensor  is  induced  by  a  single  shock  applied  to  the  intact  motor 
nerve,  the  curve  obtained  shows  a  relaxation  line  much  slower  and 
more  prolonged  than  when  the  cut  nerve  is  similarly  excited.  In  the 
latter  case,  or  when  the  posterior  roots  alone  are  divided,  the  lever  at 
the  end  of  relaxation  dips  below  the  base  line  with  an  inertia  fling, 
which  is  never  present  while  the  nerve  is  intact.  The  contraction  of 
the  muscle,  when  its  afferent  path  is  intact,  seems  to  develop  reflexly 
in  the  muscle  itself  a  condition  of  tone  which  damps  the  inertia  swing 
of  the  contraction.  In  the  dog,  after  section  of  the  afferent  nerves 
of  one  hind  limb,  this  limb  is  not  at  first  used  for  walking ;  it  is  kept 
more  or  less  flexed  at  hip  and  knee,  and  later,  when  it  is  employed  in 
walking,  it  is  lifted  too  high  with  each  step.  After  division  of  the 
afferent  fibres  of  both  limbs  these  appear  as  if  they  were  afiected 
with  motor  paralysis.  At  first,  during  walking,  the  fore  limbs  simply 
drag  the  hind  limbs  after  them,  though  later,  as  the  hind  limbs  are 
drawn  along,  they  make  alternate  movements  and  may  ultimately 
afford  a  certain  amount  of  support  to  the  body. 

Still  more  striking  effects  are  observed  in  complete  apsesthesia  of 
the  fore  limb  in  monkey  or  man.  The  limb  is  permanently  para- 
lysed; it  is  never  used  in  climbing,  or  in  the  taking  of  food.  That 
the  peripheral  motor  mechanism  is  intact  is  shown  by  the  fact  that 
stimulation  of  the  appropriate  area  of  the  cerebral  cortex  in  such 
animals  elicits  at  once  a  perfectly  normal  movement  of  the  hand  or 
limb.  It  seems,  however,  impossible  for  the  cortex  to  initiate  such 
movements  in  the  absence  of  all  afferent  impulses  arriving  from  the 
limb.  Similar  paralysis  was  observed  by  Chas.  Bell  in  the  upper  lip 
of  the  ass  after  section  of  the  corresponding  branches  of  both  fifth 
nerves,  and  was  interpreted  by  him  as  indicating  a  possible  motor 
function  for  these  nerves. 

In  these  phenomena  of  sensory  paralysis  we  are  dealing  with  the 
effects  produced  by  the  deprivation  of  two  distinct  classes  of  afferent 
impressions,  viz.  those  from  the  skin,  and  those  from  the  deep  struc- 
tures and  muscles.     The  phenomena  due  to  these  two  factors  may  be 


THE  MECHANISM  OF  CO-ORDINATED  MOVEMENTS     :J9I 

studied  separately.  If  in  the  monkey  all  the  afferent  brachial  roots 
except  the  last  cervical,  which  supplies  cutaneous  sensations  to  the 
whole  hand,  be  divided,  the  monkey  uses  the  arm  and  hand  both  in 
climbing  and  in  taking  food.  A  marked  ataxy  of  the  movement  is, 
however,  observed.  Whereas  the  normal  monkey,  in  taking  grains 
of  rice  out  of  the  observer's  hand,  exhibits  perfect  precision  of 
movement  so  that  he  rarely  touches  the  hand  on  which  the  grains 
are  lying,  the  monkey  with  only  cutaneous  sensibility  remaining 
grasps  clumsily  with  the  whole  hand,  and  the  arm  sways  as  it  is 
put  out,  often  missing  the  object  aimed  at  altogether.  Cutaneous 
insensibility  of  the  hind  limb  causes  very  little  disturbance  of 
locomotion,  the  alternate  movements  of  which  seem  to  be  started 
by  the  stretching  of  the  structures  at  the  front  of  the  thigh.  On  the 
other  hand,  a  patient  affected  with  such  a  loss  may  be  the  subject 
of  '  static  ataxy,'  i.e.  he  is  unable  to  stand  with  his  feet  together  and 
his  eyes  shut.  The  afferent  impressions  from  the  skin  of  the  feet 
appear  therefore  to  be  necessary  for  the  maintenance  of  static 
equilibrium. 

In  the  carrying  out  of  co-ordinated  movements,  such  as  those 
of  locomotion,  the  impressions  from  the  muscles  play  a  more  im-  ^ 
portant  part.  Division  of  the  afferent  nerves  from  the  muscles  gives 
rise  to  a  condition  of  tonelessness,  and  the  passive  mobihty  of  the 
joints  is  greater  than  usual,  so  that  the  hip  with  the  limb  extended 
at  the  knee  may  be  flexed  to  an  abnormal  extent.  The  effect  of 
this  loss  of  tone  is  more  apparent  in  the  case  of  certain  muscles. 
The  disturbance  of  co-ordination  resulting  from  the  cutting  off  of 
afferent  muscular  impressions  is  well  seen  in  cases  of  tabes  dorsalis, 
or  locomotor  ataxy,  in  man,  and  to  a  slighter  extent  in  cases  of 
peripheral  neuritis  affecting  chiefly  the  sensory  nerves  of  muscles.  The 
ataxic  gait  of  such  patient  is  characteristic.  There  is  no  loss  of 
power  in  the  muscles,  but  there  is  loss  of  control.  The  patient  is 
unaware  of  the  position  of  his  limbs  and  has  to  guide  his  walk  by 
visual  impressions  ;  even  then  the  movements  are  inco-ordinated. 
The  contraction  of  every  muscle  is  exaggerated,  so  that  in  walking  the 
leg  is  first  raised  too  high  and  -then  is  brought  down  on  to  the  ground 
with  a  stamp.  As  the  disease  progresses  the  loss  of  control  becomes 
more  and  more  pronounced,  so  that  attempts  to  walk  simply  give 
rise  to  a  profusion  of  disordered  movements,  the  legs  being  thrown  in 
all  directions  with  the  patient's  efforts,  but  with  no  effective  result. 
The  centres  are  no  longer  informed  of  the  degree  to  which  each  muscle 
is  contracted,  and  the  impressions  are  wanting  which  should  cut  short 
the  contraction  of  a  muscle  when  it  has  attained  its  optimum,  and 
which  should  inhibit  the  antagonists  during  the  contraction  and  induce 
activity  of  the  antagonists  in  successive  alternation  to  those  of  the 


392 


PHYSIOLOGY 


other  muscles.  In  such  a  patient  therefore  walking  finally  becomes 
impossible,  and,  with  well-nourished  muscles  and  a  motor  path  which 
is  intact,  is  condemned  to  pass  the  rest  of  his  days  in  bed. 

THE  EFFECT  OF  POISONS  ON  THE  SPINAL  CORD 
The  reflex  functions  of  the  spinal  cord  may  be  abolished  by  the 
same  drugs,  such  as  ether,  chloral,  &c.,  which  abolish  conductivity 

BODY 

prosthotonic 

NECK  . 
fuming 


BODY.    , 

-  opistnotonic 


NECK 

refraction 


FACE  \ 


Via.  17-4.     J)iagtani  ))y  iSlR'iriiigton  to  sliuw  iutlucuce  of  tetanus  toxin  on  tlif 
response  to  excitation  of  the  motor  area  of  the  cortex  in  the  moni<ey. 
A,  normal  animal.     B,  after  poisoning  with  tetanus.     F  and  /  =  flexion  of 
leg  and  arm  respectively.     E  ande  signify  extension.      <  signifies  opening  of 
mouth  ;    =  signifies  closing  of  mouth. 

in  a  nerve  fibre.  The  central  effect  of  these  drugs  is  obtained  with 
nmch  smaller  concentrations  than  is  the  case  with  the  peripheral 
nerves  and  is  the  cause  of  their  anaesthetic  effect. 

More  interesting  from  the  point  of  view  of  the  physiologist  is  the 
action  of  such  a  drug  as  strychnine,  or  the  somewhat  similar  action  of 


THE  MECHANISM  OF  CO-ORDIKATED  MOVEMENTS     ?m 

the  toxin  formed  by  the  tetanus  bacillus.  If  a  small  dose  of  strychnine 
be  injected  into  a  spinal  frog,  after  a  short  period  of  heightened 
irritability  the  slightest  stimulus  applied  to  the  surface  will  cause 
spasms,  which  may  affect  every  muscle  in  the  body.  Pinching  the 
foot,  instead  of  causing  it  to  be  drawn  up  now  causes  the  legs,  arms, 
and  back  to  be  rigidly  extended.  The  extension  is  not  a  co-ordinated 
act,  but  is  associated  with  strong  contraction  of  the  flexors,  the  final 
position  of  the  limbs  being  determined  by  the  preponderating  strength 
of  the  extensor  muscles.  The  real  meaning  of  this  condition  is  seen  if, 
in  a  spinal  mammal,  the  extensor  muscles  be  connected  with  a  lever 
and  the  flexor  muscles  cut.  On  exciting  the  flexor  reflex  by  pricking 
the  foot,  there  is  instantaneous  relaxation  of  the  extensor  muscles. 
A  small  dose  of  strychnine  is  now  given,  insufficient  to  cause  general 
convulsions.  It  is  now  found  that  on  pricking  the  foot  the  extensor 
muscles  respond,  not  Avith  inhibition,  but  with  a  contraction.  Strych- 
nine acts  by  abolishing  the  inhibitory  side  of  every  co-ordinated  act 
and  converting  the  process  of  inhibition  into  one  of  excitation.  Co- 
ordination therefore  becomes  an  impossibility,  and  stimulation  of  any 
spot  excites  contractions  not  only  of  the  appropriate  muscles  but  also 
of  the  antagonists  of  these  muscles,  the  direction  of  the  resulting  move- 
ment being  determined  simply  by  the  relative  strength  of  the  two  sets 
of  muscles. 

The  same  effect  is  produced  by  tetanus  toxin,  and,  since  the  action 
of  this  toxin  may  be  confined  in  its  early  stages  to  one  limb,  it  is 
possible  to  show  the  abolition  of  the  inhibitor  side  of  the  reflexes  in 
this  one  limb  while  the  limb  of  the  other  side  reacts  normally  to  the 
stimulus.  The  same  abolition  of  inhibition  is  found  whether  the 
response  be  excited  by  stimulation  of  the  skin  or  by  voluntary  excita- 
tion from  the  cortex  of  the  brain.  Thus  in  the  monkey,  on  stimulating 
the  cortex,  opening  of  the  mouth  may  be  excited  from  all  the  spots 
marked  "  •<  "  in  the  diagram,  closure  being  only  obtained  from  those 
spots  marked  "  =  "  (Fig.  174).  Under  the  influence  of  the  tetanus  toxin 
excitation  of  every  one  of  the  spots,  whether  "  -<  "  or  "  =,"  causes 
closure  of  the  jaw.  It  is  impossible  for  a  patient  under  these  circum- 
stances to  open  his  mouth,  because  every  willed  impulse  for  opening 
innervates  at  the  same  time  the  stronger  masseter  muscles  and  effec- 
tively closes  the  mouth. 


/ 


SECTION  IX 

TROPHIC  FUNCTIONS  OF  THE  CORD 

The  reflexes  which  are  excited  by  painful  or  nocuous  stimuli 
must  be  regarded  as  prepotent  in  that  their  inhibitory  efEect  on 
other  reflexes  is  more  marked  than  that  produced  by  any  other 
quality  of  stimulus.  In  the  struggle  for  existence  the  reaction  to 
nocuous  stimuli  must  predominate  over  those  due  to  any  other  kind, 
since  it  is  essential  for  the  survival  of  the  animal  that  the  stimulus 
should  be  removed  or  avoided,  so  that  the  animal  should  escape  from 
its  injurious  effects. 

It  is  natural  therefore  that  after  complete  section  of  the  afferent 
nerves  from  any  part  of  the  surface  of  the  body  there  should  be  a 
tendency  to  trophic  disturbances,  such  as  the  formation  of  ulcers,  &c. 
Such  ulceration  is  frequently  observed  in  patients  suffering  from 
spinal  disease.  After  section  of  the  first  division  of  the  fifth  nerve 
ulceration  of  the  cornea  is  often  produced.  These  effects  are,  however, 
merely  due  to  the  absence  of  the  normal  protective  reactions  of  the  part, 
and  can  be  prevented  by  scrupulous  cleanliness  and  protection  of  the 
apsesthetic  part  from  all  possible  injuries.  There  are  other  trophic 
effects  caused  by  nerve  lesions  which  cannot  be  ascribed  to  the  mere 
absence  of  protective  reflexes.  Thus  inflammation  of  the  posterior 
root  ganglia  often  sets  up  herpes  zoster,  or  '  shingles,'  in  the  region  of 
cutaneous  distribution  of  the  corresponding  sensory  nerve.  Changes 
in  the  skin  ('  glossy  skin  ')  nails  and  hair  are  often  seen  after  irritative 
injuries  of  nerves  to  the  part.  Section  of  a  motor  nerve  causes  rapid 
changes  in  the  skeletal  muscles  supplied,  which  become  smaller  and 
after  months  or  years  may  disappear  altogether,  being  replaced  by 
connective  tissue.  The  changes  in  the  excitability  of  the  muscles 
produced  under  these  circumstances  have  already  been  described. 

It  seems  that  the  nutrition  of  a  tissue  is  determined  by  its  activity, 

and  this  in  turn  is  under  the  control  of  some  nerve  path.     Section  of  the 

nerve  path,  by  cutting  away  the  impulses  which  normally  maintain  the 

activity  of  the  part,  must  at  the  same  time  seriously  affect  its  nutrition. 

Thus  the  muscles  which,  though  striated,  are  not  so  immediately 

under  the  control  of  the  central  nervous  system,  such  as  the  sphincter 

ani,  do  not  undergo  degeneration    after  section  of  their  nerves,  or 

after  extirpation  of  the  lower  part  of  the  spinal  cord. 

394 


TROPHIC  FUNCTIONS  OF  THE  CORD  3<)5 

On  the  other  hand,  it  is  only  during  post-foe1:al  life  that  the  activity 
of  the  skeletal  muscles  is  determined  by  the  motor  nerves  of  the  cord. 
Thus  they  may  be  developed  normally  even  in  the  complete  absence 
of  a  central  nervous  system.  Whether  we  are  justified  in  assuming  the 
existence  of  trophic  nerves  exercising  an  influence  on  the  nutrition  of 
the  part  they  supply,  apart  from  any  influence  on  its  other  functions, 
the  experimental  evidence  before  us  is  not  sufficient  to  decide  ;  nor 
can  we  as  yet  give  a  physiological  analysis  of  the  changes  in  nutrition 
which  may  be  brought  about  in  hysterical  patients  under  the  influence 
of  emotion. 


SECTION  X 

THE  SPINAL  CORD  AS  A  CONDUCTOR 

The  nervous  system  is  built  up  of  chains  of  neurons  which 
subserve  reactions  of  varying  complexity.  The  complexity  increases 
with  the  interference  of  the  higher  parts  of  the  brain  in  the  reactions 
and  becomes,  therefore,  more  and  more  marked  as  we  ascend  the 
animal  scale.  Whatever  the  course  taken  by  the  impulses  in  the 
central  nervous  system  they  must  all  finally  make  use  of  the  motor 
common  path,  represented  by  the  anterior  spinal  roots  and  by  the 
motor  roots  of  the  cranial  nerves. 

The  co-operation  in  any  co-ordinated  movement  of  widely  separated 
portions  of  the  central  nervous  system  necessitates  the  existence  of 
long  paths,  i.e.  the  axons  of  certain  nerve-cells  must  extend  through 
a  considerable  distance  in  the  central  nervous  system  before  they 
arrive  at  the  next  relay  in  the  chain  of  which  they  form  part.  During 
this  course  the  axons  run  in  the  white  matter  of  the  central  nervous 
system,  and  are  surrounded  by  medullary  sheaths.  The  white  matter 
of  the  cord  consists  almost  exclusively  of  medullated  nerve  fibres 
running  for  the  most  part  longitudinally.  These  are  of  various 
sizes,  some  of  the  smaller  fibres  being  collaterals,  which  have  been 
given  of?  from  the  larger  ones  and  which  will  shortly  turn  into  the 
grey  matter.  In  section  they  resemble  closely  the  fibres  of  an  ordinary 
peripheral  nerve,  but  differ  from  these  in  that  they  have  no  primitive 
sheath  or  neurilemma.  Each  consists  of  an  axis  cylinder  surrounded 
by  a  thick  sheath  of  myelin,  the  whole  embedded  in  a  tube  formed 
by  the  neuroglia. 

Of  these  fibres  part  belong  to  the  spinal  cord,  the  proprio-spinal  or 
internuncial  fibres,  which  we  have  studied  previously.  The  greater 
number  serve  to  establish  connection  between  the  grey  matter  of  the 
cord  or  the  afferent  roots  entering  the  cord,  and  the  different  levels 
of  the  brain,  and  these  fibres  may  carry  impulses  either  up  towards  the 
brain  or  down  towards  the  spinal  cord  ;  they  may  be  ascending  or 
afferent,  so  far  as  the  brain  is  concerned,  or  descending  and  efferent. 
No  fibre  takes  an  isolated  course  on  its  way  through  the  cord  ;  practi- 
cally every  one  sends  off  fine  branches  or  collaterals,  which  run  into 
the  grey  matter  at  various  levels,  there  making  connection  or  having 

synapses  with  the  local  reflex  mechanisms  contained  in  each  segment. 

396 


THE  SPINAL  CORD  AS  A  CONDUCTOR  :V.)7 

On  inspection  the  white  matter  is  seen  to  be  divided  by  the  anterior 
and  posterior  fissures  of  the  cord  into  two  symmetrical  halves,  and 
the  nerve-roots  divide  each  half  into  anterior  or  ventral,  lateral,  and 
posterior  or  dorsal  columns.  On  account  of  the  scattered  distribu- 
tion of  the  anterior  root  fibres  over  a  considerable  area  of  the  surface 
of  the  cord,  the  division  between  the  anterior  and  the  lateral  columns 
is  ill  defined,  and  the  whole  region  is  often  defined  as  the  antero-lateral 
column.  In  the  cervical  and  upper  dorsal  region  of  the  cord  slight 
grooves  on  the  surface  of  the  cord  indicate  a  division  of  the  anterior 
column  into  the  antero-median  and  antero-lateral  columns,  and 
of  the  posterior  column  into  the  postero-median  and  postero-lateral 
columns.  These  two  posterior  columns  are  often  designated  as  the 
columns  of  Goll  and  Burdach.  In  order  to  determine  the  origin, 
course,  and  destination  of  the  fibres  which  make  up  these  white  columns 
we  must  have  recourse  to  the  indirect  methods  of  development  and 
of  degeneration  which  were  described  on  p.  359.  By  these 
means  we  may  divide  the  white  matter  into  ascending  and  descending 
tracts.  An  '  ascending  '  tract  means,  not  that  the  direction  of  con- 
duction of  the  impulse  is  necessarily  in  the  upward  direction,  i.e. 
from  spinal  cord  to  brain,  but  that  the  nerve-cell  which  gives  off  the 
fibres  sends  its  axons  towards  the  brain,  while  a  descending  fibre  in 
the  cord  is  the  axon  of  a  nerve-cell  situated  in  the  upper  part  of  the 
cord,  or  in  some  part  of  the  brain.  If  the  assumption  which  we  have 
made  as  to  the  normal  direction  of  conduction  in  axons  and  dendrites 
be  correct,  an  ascending  fibre  will  also  conduct  impulses  in  an  ascend- 
ing direction.  After  section  of  the  cord,  say  in  the  mid-dorsal  region, 
transverse  sections  of  the  cervical  and  lumbar  regions  of  the  cord, 
taken  at  the  appropriate  period  after  the  lesion  has  been  inflicted, 
show  patches  of  degenerated  fibres  in  the  white  matter.  The  fibres 
which  are  degenerated  above  the  section  represent  the  ascending 
tracts,  whereas  those  which  degenerate  below  the  section,  i.e.  in  the 
lumbar  region,  are  the  descending  tracts  of  the  cord  {cp.  Figs.  175  and 
17r>).     Ill  this  way  the  following  tracts  have  been  distinguished  : 

A.  DESCENDING  TRACTvS 
(1)  PYRAMIDAL  TRACTS.  If  the  spinal  cord  be  divided  in  the 
upper  cervical  region,  degeneration  of  two  distinct  tracts  on  each  side, 
in  the  anterior  and  postero-lateral  columns,  is  produced.  These  are 
the  anterior  or  direct  and  the  crossed  pyramidal  tracts.  The  fibres 
composinji;  these  tracts  are  derived  from  large  nerve-cells  in  the 
motor  area  of  the  cerebral  cortex,  and  therefore  degenerate  if  the 
motor  area  of  the  cortex  is  destroyed.  The  pyi'amidal  tracts  are 
derived  from  the  cerebral  cortex  of  the  ojiposite  side,  having  crossed 
the  middle  line  at  the  lower  level    of    the   meiluUa  ol)longata  in  the 


398 


PHYSIOLOGY 


pyramidal  decussation.  The  anterior  pyramids  represent  a  certain 
number  of  fibres  which  have  not  crossed  with  the  others,  but  continue 
the  course  of  the  medullary  jjyramids  for  a  time,  crossing  gradually  by 
the  anterior  commissure  on  their  way  down  the  cord,  so  that,  as  a 
rule,  they  come  to  an  end  in  the  mid-dorsal  region,  all  the  fibres 
having  passed  into  the  lateral  columns  of  the  opposite  side.  A  few 
fibres  of  the  pyramids  on  their  way  from  the  cerebral  cortex  pass  into 
the  lateral  columns  of  the  same  side  ;  these  are  the  uncrossed  pyra- 
midal fibres.  The  greater  number  of  the  fibres,  however,  finally  reach  the 
crossed  pyramidal  tracts,  in  which  they  can  be  traced  as  far  as  the  lower 
end  of  the  cord.  They  end  in  the  spinal  cord  by  turning  into  the  grey 
matter  and  there  breaking  up  into  a  fine  bunch  of  fibrils  in  close 


sfi.L 


I    - 


Fig.  175.  Diagram  (jrom  Schafer)  showing  the  ascending  (right  side) 
and  the  descending  (left  side)  tracts  in  the  spinal  cord. 
1,  crossed  pyramidal;  2,  direct  pyramidal;  3,  antero -lateral  descending; 
3a,  spino-olivary  descending  (bundle  of  Helweg)  ;  4,  pre-pyramidal  (rubro- 
spinal) ;  5,  comma ;  6,  postero-mesial ;  7,  postero-lateral ;  8,  Lissauer's^ 
tract ;  9,  dorsal  (ascending)  cerebellar ;  10,  antero -lateral  ascending  ; 
sm,  septo-marginal ;  S'pl,  dorsal  root  zone  ;  a,  anterior  horn-cells  ;  i,  inter- 
medio-lateral  horn  ;  f,  cells  of  posterior  horn  ;  d,  Clarke's  column.  The 
fine  dots  represent  the  situation  of  the  '  internuncial '  or  '  endogenous  ' 
fibres  of  the  spinal  cord. 

connection  with  the  motor-cells  of  the  anterior  cornu,  or,  according 
to  Schafer,  with  the  cells  of  the  posterior  horn. 

On  their  way  down  the  cord  they  give  off  fine  side  branches  or 
collaterals,  which  run  into  the  grey  matter,  thus  establishing  connec- 
tions between  one  cortical  cell  and  the  anterior  cornual  cells  of  several 
different  segments  of  the  spinal  cord.  These  fibres  carry  voluntary 
motor  impulses  from  the  cerebral  cortex  to  the  reflex  motor  mechanisms 
of  the  cord.  Their  destruction  by  disease,  or  otherwise,  causes  the 
abolition  of  voluntary  control  over  the  muscles,  without,  however, 
interfering  with  the  reflex  motor  functions  of  the  cord,  which,  as  a 
matter  of  fact,  are  increased  in  cases  where  these  tracts  have  under- 
gone degeneration. 


THE  SPINAL  CORD  A.S  A  CONDLX'TOR  399 

c {-2)  RUBRO-SPINAL    OR    PREPYRAMIDAL   TRACT    (also   called 

Mouakow's  Bundle).  This  is  a  fairly  compact  group  of  fibres  which 
degenerate  downwards  after  section  of  the  cord.  It  is  situated,  in 
cross-section,  ventral  to  the  pyramidal  tracts.  Its  fibres  can  be 
traced  up  to  the  cells  in  the  red  nucleus,  a  mass  of  grey  matter  in  the 
mid-brain  lyinfi  ventrally  to  the  nucleus  of  the  third  nerve. 

(3)  VESTIBULO-SPINAL  TRACT.  This  consists  of  scattered 
fibres  in  the  antero-lateral  column,  which  degenerate  in  the  downward 
direction.  They  were  formerly  supposed  to  be  derived  from  the 
cerebellum  of  the  same  side,  but  it  has  been  shown  that  they  are  in 
all  probability  derived  from  Deiter's  nucleus  in  the  medulla — an 
important  transmitting  station  between  the  cerebellum  and  cord. 

^  (4)  OLIVO- SPINAL  AND  THALAMICO-SPINAL  TRACTS  (Bundle 
of  Helweg).  This  tract  is  also  situated  in  the  antero-lateral  column, 
opposite  the  head  of  the  anterior  horn.  It  consists  mainly  of  fibres 
which  pass  from  the  thalamus  (the  fore  brain)  through  the  inferior 
olive  of  the  medulla  downwards  in  the  cord  as  far  as  the  lower  cervical 
region. 

(5)  COMMA  TRACT.  This  tract  hes  in  the  posterior  columns  at 
the  junction  of  the  postero-median  and  postero-lateral  portions.  It 
consists  for  the  most  part  of  the  descending  branches  of  the  afferent 
dorsal  nerve-roots  which  enter  the  cord.  These  dix-ide  as  they  enter 
the  cord,  and  their  descending  branches  pass  down  for  two  or  three 
segments  in  the  comma  tract  before  turning  into  the  grey  matter. 
The  tract,  however,  contains  fibres  of  other  origin,  some  of  which 
begin  and  end  in  the  spinal  cord  itself. 

(6)  TRACT  OF  MARIE.  This,  also  in  the  anterior  column, 
contains  both  descending  and  ascending  fibres  and  is  largely  a  continua- 
tion of  the  posterior  longitudinal  bundle,  the  connections  of  which 
we  shall  have  to  study  later  on.  A  small  tract  of  fibres,  which  degene- 
rate in  the  descending  direction,  is  also  found  in  the  posterior  part 
of  the  cord  adjoining  the  posterior  longitudinal  fissure. 

(7)  SEPTO-MARGINAL  BUNDLE.  This  is  largely  proprio-spinai, 
but  may  contain  fibres  coming  from  the  mid-brain. 

B.     ASCENDING  TRACTS 

These  may  be  divided  according  as  tliey  are  situated  in  the  posterior, 
the  lateral,  or  the  anterior  columns. 

(a)  THE  POSTERIOR  COLUMNS.  Almost  the  whole  of  the  fibres 
making  up  these  columns  are  not  derived  from  cells  in  the  spinal 
cord,  but  are  exogenous,  being  axons  of  cells  in  the  posterior  root 
ganglia.  They  can  be  divided  into  long,  medium,  and  short  fibres, 
all  of  which,  ascending  vertically  in  these  columns,  give  off  collaterals, 
which    pass   into    the    grey   matter  and   ramify   round    nerve-cells, 


v/ 


400 


PHYSIOLOGY 
I  III 


II 


IV 


VII 


VI 


VIII 


Fig.  176.  Diagram  of  sections  of  the  spinal  cord  of  the  monkey  showing  the  position 
of  degenerated  tracts  of  nerve  fibres  after  specific  lesions  of  the  cord  itself,  the 
afferent  nerve-roots,  and  of  the  motor  region  of  the  cerebral  cortex.  (Schafer.) 
(The  degenerations  are  shown  by  the  method  of  Marclii.)  The  left  side  of  the 
cord  is  at  the  reader's  left  hand. 

I.  Degenerations  resulting  from  extirpation  of  the  motor  area  of  the  cortex  of 
the  left  cerebral  hemisphere. 

II.  Degenerations  produced  by  section  of  the  posterior  longitudinal  bundk's 
in  the  upper  part  of  the  medulla  oblongata. 

III.  and  IV.  Result  of  section  of  posterior  roots  of  the  first,  second,  and  third 
lumbar  nerves  on  the  right  side.  Section  III.  is  from  the  segment  of  cord  between 
the  last  thoracic  and  first  lumbar  roots  ;  section  IV.  from  the  same  cord  in  the 
cervical  region. 

V.  to  VIII.  Degenerations  resulting  from  (right)  semi-section  of  the  cord  in 
the  upper  thoracic  region.  V.  is  taken  a  short  dist:ince  above  the  level  of  section  ; 
VI.  higher  up  tlie  cord  (cervical  region)  ;  VII.  a  little  below  the  level  of  section  ; 
VIII.  lumbar  region. 


THE  SPINAL  CORD  A8  A  CONDUCTOR  401 

especially  in  the  posterior  horns  {cp.  Fig,  161).  The  longest  fibres  pass 
to  the  upper  end  of  the  cord,  where  they  end  in  the  posterior  column 
nuclei,  the  nucleus  gracilis  and  the  nucleus  cuneatus  of  the  medulla. 
These  fibres  remain  entirely  on  the  side  of  the  cord  on  which  they 
have  entered.  As  they  pass  up  they  are  displaced  towards  the  middle 
Hne  by  each  incoming  and  higher  placed  root.  Thus  in  the  cervical 
legion,  and  indeed  from  the  fifth  dorsal  segment  upwards,  two  columns 
can  be  distinguished  in  the  posterior  part  of  the  cord,  viz.  the  postero- 
median and  postero- lateral  columns,  the  division  between  which  is 
indicated  by  a  small  gi'oove  on  the  surface.  The  postero- median 
column  contains  from  within  outwards  the  fibres  from  the  sacral  region, 
those  from  the  lumbar  region,  and  those  from  the  inferior  dorsal 
region.  The  postero-lateral  column,  or  column  of  Burdach,  contains 
mesially  the  four  upper  dorsal  root  fibres  and  more  laterally  the  fibres 
from  the  cervacal  nerves. 

(6)  THE  LATERAL  COLUMNS.  In  these  columns  are  found  the 
two  cerebellar  tracts,  as  well  as  scattered  fibres  passing  to  the  tore- 
and  mid-brain. 

(1)  The  Direct  or  Dorsal  Cerebellar  Tract  arises  from  the 
cells  of  Clarke's  column  on  its  own  side.  It  consists  of  large  fibres, 
which  pass  through  the  gxey  matter  to  the  lateral  columns  of  the  same 
side,  and  ascend  in  the  cord  immediately  ventral  to  the  incoming 
posterior  root  fibres,  and  external  to  the  crossed  pyramidal  tract.  In 
the  medulla  they  are  joined  by  a  bundle  of  fibres  from  the  opposite 
inferior  olive  and  pass  with  the  restiform  body  into  the  cerebellum, 
where  they  terminate  in  the  superior  vermis  of  this  organ. 

(2)  The  Ventral  or  Anterior  Cerebellar  Tract,  often  called 
the  tract  of  Gowers,  arises  in  cells  scattered  through  the  grey  matter, 
chiefly  of  the  pos^rior  horn  of  the  opposite  side,  though  a  few  fibres  are 
derived  from  cells  of  the  same  side.  The  tract  consists  of  fine  fibres 
which  pass  upwards  in  the  peripheral  margin  of  the  lateral  column, 
extending  from  the  direct  cerebellar  tract  behind  to  the  level  of 
the  anterior  roots  in  front ;  it  passes  upwards  through  the  cord,  the 
medulla,  and  the  pons,  then  turns  round  to  enter  the  cerebellum 
through  the  superior  cerebellar  peduncle,  ending  chiefly  in  the  ventral 
portion  of  the  superior  vermis. 

(3)  The  Spino-thalamic  and  Spino-tectal  Tr.\cts.  These  fibres 
form  a  scattered  bundle  lying  internally  to  the  anterior  cerebellar 
tract,  and  are  practically  part  of  Gowers' tract.  They  may  be  traced 
through  the  cord,  medulla,  and  pons  and  end,  partly  in  the  anterior 
corpora  quadrigemina  of  both  sides,  but  to  a  greater  extent  in  the 
optic  thalamus  of  the  same  side. 

(c)  ANTERIOR  COLUMNS.  A  number  of  scattered  fibres  pass  up 
the  anterior  columns,  mingled  with  the  descending  fibres  of  the  tract 

26 


402  •  PHYSIOLOGY 

of  Marie  in  the  angle  of  the  anterior  fissure.  Others  pass  up  with 
Helweg's  bundle  partly  to  end  in  the  olivary  body,  partly  to  run  on 
with  the  mesial  fillet  towards  the  thalamic  region. 

The  white  matter  of  the  cord  can  thus  be  regarded  as  made  up  of 
short  and  of  long  tracts,  which  maintain  direct  connection  between 
the  following  parts  of  the  central  nervous  system  : 

(1)  Different  levels  of  the  cord  itself  by  means  of  the  proprio- 
spinal  fibres. 

(2)  Hind-brain  and  spinal  cord,  by  the  anterior  and  posterior 
cerebellar  tracts,  the  posterior  columns,  and  the  spino-olivary  fibres 
among  the  ascending  tracts,  and  the  vestibulo-spinal  and  olivo-spinal 
among  the  descending  tracts. 

(3)  The  mid-brain  and  cord  connections  are  represented  by  the 
spino-tectal  tracts  in  the  lateral  columns  as  a  direct  ascending  path,  and 
by  the  rubro-spinal  tract  which  furnishes  a  direct  efferent  connection 
between  mid-brain  and  cord. 

(4)  The  fore-brain,  viz.  the  thalamus,  receives  only  a  few  scattered 
fibres — spino- thalamic,  which  run  chiefly  in  the  lateral  and  anterior 
columns.     It  has  no  direct  efferent  path  to  the  cord. 

(5)  The  cerebral  cortex,  the  master  tissue  of  the  body,  receives 
no  fibres  directly  from  the  cord  or  periphery  of  the  body,  but  by  the 
pwamidal  tracts  is  able  to  influence  directly  the  activities  of  the 
motor  mechanisms  at  every  level  of  the  cord.  These  fibres,  so  far  as 
is  known,  exist  only  in  mammals,  and  show  a  great  increase  in  relative 
extent  when  traced  from  lower  to  higher  types.  While  in  the  rabbit 
the  pyramidal  tract  is  hardly  perceptible,  in  the  monkey  it  is  the  best 
marked  of  all  the  tracts,  and  in  man  is  still  more  highly  developed. 
This  relative  increase,  which  is  probably  associated  with  the 
shunting  of  more  and  more  of  the  reactions  of  the  body  from  the 
region  of  the  unconditioned  reflexes  to  that  of  the  educatable  re- 
action,  is  shown  not  merely  by  the  tract  occupying  a  larger  proportion 
of  the  transverse  area  of  the  cord,  but  by  its  fibres  being  more  densely 
set  within  that  area. 

THE  PATHS  OF  IMPULSES  IN  THE  CORD 
The  greater  part  of  the  white  matter  is  thus  concerned  in  trans- 
mitting impulses  to  nerve-cells  in  the  brain,  and  from  the  brain 
towards  the  cord.  The  complex  reactions  determined  by  these 
impulses  are  in  many  cases  as  unconscious  and  automatic  as  those  we 
have  studied  in  the  spinal  cord,  even  though  they  may  involve  the 
activity  of  the  cerebral  cortex  itself.  Others,  however,  influence 
consciousness,  so  that  their  afferent  side  appears  in  consciousness  as 
sensations  of  various  qualities,  and  their  efferent  side  as  the  result 
of  volition,  i.e.  as  willed  or  emotional  movements. 


THE  SPIXAL  CORD  AS  A  CONDUCTOR  403 

The  posterior  spinal  (sensory)  roots  at  their  entrance  into  the 
cord  divide  into  two  bundles.  The  smaller  of  the  two,  situated  more 
laterally  and  consisting  of  fine  fibres,  enters  opposite  the  tip  of  the 
posterior  horn  and  turns  up  at  once  in  Lissauer's  tract,  a  bundle  of 
fine  longitudinal  fibres  close  to  the  periphery  of  the  cord.  The  fibres 
seem  to  pass  into  and  end  in  the  substance  of  Rolando.  The  larger 
median  bundle  of  coarse  fibres  passes  into  the  postero-extemal 
column.  Here  each  fibre  divides  into  a  descending  and  an  ascending 
branch,  the  former  running  in  the  comma  tract,  the  latter  in  the  poste- 
rior columns  up  as  far  as  the  gracile  and  cuneate  nuclei  of  the  medulla. 
Both  of  these  branches  give  off  collaterals  in  the  whole  of  their  course, 
most  numerous  near  the  point  of  entry  of  the  nerve.  These  collaterals 
may  be  divided  into  four  sets  according  to  their  destination  : 

(1)  Fibres  ending  round  cells  of  anterior  horn  on  same  side  or 
crossing  by  posterior  commissure  to  grey  matter  on  other  side. 

(2)  Fibres  ending  in  grey  matter  of  posterior  horns. 

(3)  Fibres  ending  round  cells  of  Clarke's  column. 

(4)  Fibres  to  lateral  horn. 

Since  the  motor  nerves  arise  from  the  anterior  horn-cells,  the 
first  set,  the  '  sensori-motor '  collaterals,  represent  the  shortest  possible 
spinal  reflex  path.  The  second  group  may  also  represent  a  spinal 
reflex  path  with  two  relays  of  cells,  and  therefore  greater  choice  of 
response  and  longer  reaction  time.  The  third  set  puts  into  action  the 
cerebellar  tracts  which  arise  from  the  cells  of  Clarke's  column,  and 
therefore  call  into  play  a  much  more  complicated  mechanism,  the 
limits  of  whose  action  it  would  be  difficult  to  define.  The  collaterals 
to  the  lateral  horn  probably  represent  the  afferent  tracts  of  the 
various  visceral  and  vaso-motor  reflexes  which  we  shall  study  later. 

In  dealing  with  the  reflexes  involving  the  co-operation  of  the 
brain,  we  find  no  special  tracts  devoted  to  those  impulses  which 
affect  consciousness  as  sensations.  All  tracts  going  towards  the 
cerebral  hemispheres  are  interrupted  by  cell  relays,  in  the  medulla  or 
cerebellum,  and  must  serve  as  afferent  channels  for  unconscious  as 
well  as  for  conscious  reactions.  The  quality  of  an  afferent  impulse 
can  only  be  defined  by  its  origin,  or  by  its  effect  on  consciousness, 
and  much  discussion  has  arisen  as  to  the  exact  path  of  the  various 
cutaneous  and  muscular  sensations  in  the  cord. 

It  is  evident  that  an  impulse  may  travel  to  the  cortex  by  wav  of 
the  two  cerebellar  tracts  through  the  cerebellum,  or  by  way  of  the 
posterior  columns  through  the  intermediation  of  the  bulbar  nuclei,  or 
by  a  series  of  relays  from  one  segment  of  the  cord  to  another  tlirough 
grey  and  white  matter  alternately.  It  is  supposed  that  all  of  the 
ascending  tracts  may  convey  afferent  impulses  from  the  posterior 
spinal  roots  to  the  brain,  although  evidence  as  to  the  part  taken  by 


404  PHYSIOLOGY 

each  tract  is  very  conflicting.  The  following  account  represents 
the  views  which  may  be  regarded  as  the  most  probable  (Page  May) 
(Fig.  177)  :  Pain  impulses,  on  entering  the  cord  by  the  posterior 
roots,  cross  to  the  other  side  at  once,  and  then  pass  Up,  chiefly  in  the 
antero-lateral  ascending  tract  of  Gowers,  as  far  as  the  optic  thalamus. 
Sensations  of  heat  and  cold  take  a  very  similar  course.  Hence  they 
are  generally  affected  by  lesions  of  the  cord  in  the  same  way  as  pain 
sensations.  Impulses  of  touch  and  pressure,  after  entering  the 
cord,  pass  up  in  the  posterior  column  of  the  same  side  for  four  or 
five  segments,  then  cross  gradually  and  pass  up  in  the  opposite  anterior 
column.  ,  Impulses  serving  muscular  sensibility,  including  the  impulses 
from  joints  and  tendons,  take  two  courses.  Those  which  do  not 
reach  consciousness,  and  are  involved  in  the  involuntary  guidance 
of  muscular  movements,  run  up  chiefly  in  the  anterior  and  posterior 
cerebellar  tracts  of  the  same  side.  Those  which  furnish  the  material 
for  conscious  sensations  and  give  information  as  to  the  jDosition  of 
the  limbs,  &c.,  are  entirely  homolateral,  and  travel  up  in  the  posterior 
columns  of  the  same  side  of  the  cord.  All  impulses  which  reach  the 
brain  cross  finally  to  the  optic  thalamus  and  thence  to  the  cerebral 
cortex  of  the  opposite  side. 

Hemisection  of  the  cord  on  one  side,  as  was  first  pointed  out  by 
Brown  Sequard,  causes  the  following  symptoms  : 

(1)  Paralysis  of  the  voluntary  motor  conductors  on  the  same  side. 

(2)  A  paralysis  also  of  the  vaso-motor  conductors  on  the  same 
side,  and,  as  a  consequence,  a  greater  afflux  of  blood,  and  a  higher 
temperature.  There  may  be  some  degree  of  hypersethesia  on  this 
side. 

(3)  There  is  ansesthesia  affecting  all  kinds  of  sensibiHty,  excepting 
the  muscular  sense,  in  the  opposite  side  to  that  of  the  lesion,  owing 
to  the  fact  that  the  conductors  of  sensitive  impressions  from  the 
trunk  and  limbs  decussate  in  the  spinal  cord  ;  so  that  an  injury  in 
the  cervical  region  of  that  organ  in  the  right  side,  for  instance,  alters 
or  destroys  the  conductors  from  the  left  side  of  the  body. 

(4)  There  is  some  degree  of  anaesthesia  also  on  the  side  of  the 
lesion,  in  a  very  Hmited  zone,  above  the  hypersesthetic  parts,  and 
indicating  the  level  of  the  lesion  in  the  cord.  This  anaesthesia  is  dne 
to  the  fact  that  the  conductors  of  sensory  impressions,  reaching  the 
cord  through  the  posterior  roots,  at  the  level  or  a  little  below  the  seat 
of  the  alteration,  have  to  pass  through  the  altered  part  to  reach  the 
other  side  of  the  cord. 

The  only  direct  unbroken  cortico-spinal  fibres  are  those  contained 
in  the  pyramidal  tracts.  Motor  impulses,  which  start  from  the 
cerebral  cortex  on  one  side,  pass  down  that  side  till  they  reach  the 
lower  part  of  the  medulla.     Here  the  greater  number  of  the  fibres 


THE  SPINAL  CORD  AS  A  CONDUCTOR 


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406  PHYSIOLOGY 

cross  over  in  the  pyramidal  decussation  to  run  down  in  the  crossed 
pyramidal  tract  on  the  other  side  of  the  cord.  The  few  fibres  which 
do  not  cross  over  in  the  pyramidal  decussation  are  continued  as  the 
direct  or  anterior  pyramidal  tract.  These,  however,  also  cross  to  the 
other  side  in  their  passage  down  the  cord  before  becoming  connected 
with  the  anterior  cornual  cells.  Hemisection  therefore  of  the  spinal 
cord  in  the  dorsal  region  will  produce  paralysis  of  motion  and  loss 
of  or  impaired  sensation  in  the  parts  supplied  by  the  nerves  on  the 
same  side  below  the  lesion. 

A  great  part  of  the  white  matter  of  the  cord  is  concerned  then  in 
maintaining  connection  between  the  brain  and  higher  parts  of  the 
nervous  system  and  the  periphery,  through  the  intermediation  of  the 
cells  of  the  gxey  matter  of  the  cord.  Corresponding  to  this  function 
we  find  a  gradual  increase  in  the  number  of  fibres  in  the  white  matter  as 
we  ascend  from  the  sacral  part  of  the  cord  to  the  medulla,  the  white 
matter  being  continually  reinforced  as  it  ascends  the  cord  by  fibres 
establishing  connection  with  the  ganglion-cells  forming  the  nuclei  of 
the  nerve- roots. 

Vaso-motor  impulses  to  the  limbs  travel  down  the  lateral  columns 
of  the  cord  on  the  same  side. 


THE   BliAlN 

SECTION  XI 

THE  STRUCTURE   OF  THE  BRAIN  STEM 

The  physiology  of  the  brain  falls  naturally  into  two  main  divisions, 
namely,  that  of  the  brain  stem,  including  the  medulla,  the  pons. 
Sylvian  iter,  corpora  quadrigemina  and  third  ventricle,  and  that  of 
the  cerebral  hemispheres.  It  is  usual,  in  treating  of  the  structure  of 
the  brain  stem,  to  consider  it  as  a  prolongation  forwards  of  the  spinal 
cord  and  as  consisting,  like  this,  of  a  central  tube  of  grey  matter 
surrounded  by  a  tube  of  white  matter.  Like  the  spinal  cord,  the 
brain  stem  may  be  regarded  as  originating  primitively  by  the  fusion 
of  a  series  of  ganglia  presiding  over  the  local  reactions  of  their  respective 
somites.  The  modifications  in  this  segmental  arrangement,  which 
have  occurred  in  the  course  of  evolution,  have  been  so  profound  that 
little  trace  of  the  primitive  segmental  arrangement  is  to  be  observed. 
At  the  fore  end  of  the  body  have  been  developed  the  organs  of  special 
sense,  which  are  the  most  important  in  determining  the  reactions 
of  the  animal  in  response  to  present  or  approaching  changes  in  its 
environment.  Indeed  the  whole  course  of  evolution  is  conditioned 
by  the  evolution  of  the  brain  stem  in  the  first  place,  and  of  its  out- 
gro^^i:h,  the  cerebral  hemispheres,  in  the  second.  Hence  we  camiot 
expect  to  find  in  the  brain  stem  the  regularity  of  arrangement 
of  grey  and  white  matter  that  we  have  studied  in  the  cord.  The 
typical  division  of  the  grey  matter  into  comua  becomes  altogether 
lost.  While  some  nerves  take  their  origin  from  or  terminate  in  the 
central  tube  of  grey  matter,  in  other  cases  the  collections  of  nerve 
cells  and  fibres  forming  the  nuclei  of  the  cranial  nerves  have  become 
more  or  less  separated  from  the  central  axis.  Moreover  the  central 
grey  matter  is  by  itself  quite  inadequate  to  deal  ^vith  the  flood  of 
afferent  impressions  entering  the  central  nervous  system  through  the 
organs  of  special  sense,  or  to  co-ordinate  these  with  one  another  or 
with  those  arriving  from  the  skin  and  lower  part  of  the  body.  Masses 
of  grey  matter,  which  have  no  representative  in  the  cord,  make  their 
appearance,  and  may  be  regarded  as  additional  sorting  stations  or 
fields  of  conjunction  for  the  play  of  afferent  and  efferent  impulses 
which  make  up  the  nervous  activities  of  the  animal. 

407 


408 


PHYSIOLOGY 


The  general  features  of  the  structure  of  the  brain  will  be  best 
understood  by  reference  to  the  mode  of  development  of  this  part  of  the 
central  nervous  system.  At  the  front  end  of  the  body,  the  primitive 
neural  tube,  formed  by  the  invagination  and  growing  over  of  the 
epiblast,  is  somewhat  enlarged  and  is  marked 
off  by  two  constrictions  into  the  three  primitive 
cerebral  vesicles,  which  are  named  respectively 
the  fore-,  the  mid-,  and  the  hind-brain,  or  the 
prosencephalon,  the  mesencephalon,  and  the 
rhombencephalon  (Fig.  178).  At  their  first 
formation  the  walls  of  these  vesicles  are  com- 
posed of  simple  epithehal  cells,  and  show  no 
trace  of  nervous  structure.  A  little  later  the 
cells  forming  the  walls  present  a  differentiation 
into  neuroblasts  and  spongioblasts^  the  former 
Fig.  178.   Diagi-amoftbe  developing    into    nerve-cells,   while   the   latter 

cerebral  vesicles  ot   the  r     o  '_  _ 

brain  of  a  chick  at  the  form  the   neuroglial  supporting  tissues  of  the 
second  day.    (Cadiat.)    ^^^-^  ^^^  probably  also  furnish  the  cells  of 

1,  2,  3,  cerebral  vesi-      ,  ,         ,  »     ri  i 

cles ;  0,  optic  vesicles,  the  sheath  ot  bchwann  to  the  outgTOwmg 
cranial  nerves.  fn  some  places  the  wall  of 
the  vesicles  remains  undifferentiated ;  no  nervous  tissues  develop  in 
it,  and  it  forms  a  layer  of  epithelium  known  as  efendyma.  By  the 
varying  growth  of  nervous  tissue  in  different  parts  of  the  wall,  the 
typical  structure  of  the  adult  brain  is  brought  about  (Fig.  179). 
Thus  in  the  hind-brain,  or 
rhombencephalon,  the  roof 
of  the  neural  canal  pos- 
teriorly fails  to  develop,  so 
that  in  the  adult  brain 
there  is  merely  a  layer  of  ©if 
epithelium  covering  the  ex- 
panded central  canal,  here 
known  as  the  fourth  ven- 
tricle. This  back  part  of 
the  hind-brain  is  often  called 
the  myelencephalon,  the  an- 
terior portion  being  the 
metencephalon.  The  floor 
of    the    myelencephalon 

undergoes  considerable  thickening  and  forms  the  future  medulla 
oblongata.  In  the  metencephalon,  nervous  tissue  is  developed  all 
round  the  canal,  the  floor  of  the  canal  forming  the  pons  Varolii,  while 
the  cerebellum  is  developed  by  an  outgrowth  of  the  dorsal  wall.  In 
the  region  of  the  constriction  between  the  hind-and  mid-brain  known 


Fig.  179.  Longitudinal  section  through  brain  of 
chick  of  ten  days.  (After  Mihalkovicz.) 
olf,  olfactory  lobes ;  h,  cerebral  hemisphere  ; 
Iv,  lateral  ventricle ;  pin,  pineal  gland  ;  bg,  cor- 
pora bigemina  ;  cbl,  cerebellum  ;  oc,  optic  com- 
missure ;  pit,  pituitary  body  ;  pv,  pons  Varolii ; 
mo,  medulla  oblongata  ;  v^,  r*,  third  and  fourth 
ventricles. 


THE  STRUCTURE  OF  THE  BRAIX  STEM  409 

as  the  isthmus,  the  roof  or  dorsal  wall  forms  the  superior  cerebellar 
peduncles  at  the  side,  and  between  them  a  thin  layer  of  nervous  matter 
known  as  the  valve  of  Vieussens,  or  superior  medullary  velum.  The 
cavity  of  the  third  vesicle  corresponds  in  the  adult  brain  to  what  is 
known  as  the  fourth  ventricle. 

The  mesencephalon,  or  second  cerebral  vesicle,  takes  a  relatively 
small  part  in  the  formation  of  the  adult  human  brain,  though  very 
conspicuous  in  many  of  the  lower  types  of  brain.  The  whole  of  its  wall 
is  transformed  into  nervous  tissue,  the  roof  or  dorsal  wall  forming  the 
corpora  quadrigemina,  while  the  two  crura  cerebri  are  developed  in  its 
ventral  wall.  The  cavity  of  the  second  cerebral  vesicle  is  retained  as  a 
narrow  canal,  known  as  the  aqueduct  of  Sylvius,  and  connects  the 
fourth  ventricle  with  the  third  ventricle. 

Very  soon  after  its  first  appearance  the  first  cerebral  vesicle  is 
modified  by  the  formation  of  lateral  expansions,  known  as  the  optic 
vesicles,  which  later  on  are  constricted  off  from  the  central  part  of 
the  cavity  so  as  to  be  connected  with  this  by  two  short  tubular  passages, 
the  optic  stalks-.  From  the  optic  vesicles  are  ultimately  developed 
the  retinae  of  the  eyes.  By  the  development  of  nerve-cells  in  the  optic 
cuj)  the  ganglion-cell  layer  of  the  retinae  is  produced,  and  from  these  cells 
fibres  grow  back  along  the  optic  stalk  and  make  connection  with  the 
grey  matter  developed  in  the  lateral  wall  of  the  fore-brain  and  with  the 
adjacent  parts  of  the  mid-brain,  viz.  the  superior  corpora  quadrigemina. 
The  large  masses  of  nervous  tissue  developed  in  the  lateral  walls  of  the 
fore-brain  are  the  optic  thalami,  which  represent  the  head  ganglia  of 
the  brain  stem.  The  front  portion  of  the  first  cerebral  vesicle  expands 
in  a  forward  and  downward  direction,  and  from  the  upper  and  lateral 
aspects  of  the  outgrowth  thus  formed  the  cerebral  hemispheres  are 
produced  as  two  hollow  pouches.  The  original  back  part  of  the  fore- 
brain  is  sometimes  spoken  of  as  the  diencephalon,  while  the  anterior 
part  of  the  cerebral  hemisphere  giowing  from  it  is  the  telencephalon. 
The  floor  or  ventral  wall  of  the  fore-brain  undergoes  moderate  thicken- 
ing to  form  the  nervous  structures  which  occupy  the  '  interpeduncular 
space  '  at  the  base  of  the  brain,  viz.  the  posterior  perforated  spot, 
the  corpora  mammilaria  and  the  tuber  cinereum.  The  root  of  the 
first  cerebral  vesicle  remains  thin  and  in  its  primitive  epithelial  condi- 
tion, like  the  roof  of  the  back  part  of  the  fourth  ventricle. 

In  the  course  of  development  the  cerebral  hemispheres  become 
larger  than  the  whole  of  the  rest  of  the  brain  put  together,  growing 
backwards  over  the  latter  as  far  as  the  middle  of  the  cerebellum 
(Fig.  180).  Their  dorsal  and  lateral  walls  become  much  thickened 
and  consist  of  white  matter  internally  and  gi-ey  matter  externally. 
The  part  of  the  hemisphere  which  lies  over  the  first  cerebral  vesicle  is 
undifferentiated  and  remains  as  a  simple  epithelial  layer.     This  becomes 


410 


PHYSIOLOGY 


closely  applied  to  the  similar  layer  forming  the  roof  of  the  third 
ventricle,  from  which  it  is  separated  only  by  a  process  of  the  pia  mater 
carrying  numerous  blood-vessels  (the  velum  inter fositum).  In  the 
adult  brain  the  cavities  of  the  cerebral  hemispheres  are  known  as  the 


Lamina  teniiinalis 

Optic  recess 

Optic  nerve 

Ojitic  commissure 

Hypopliysis 

Anterior  commissure 
Foramen  of  Monro 
3rd  nerve 
Corpus  mammillare 
3rd  ventricle 
Cerebral  pedunch 

Pons 
Suprapineal  recess 

Pineal  body 
Cerebral  aqueduct 


jv  Cerebellum 

,  ■    ,  \  Medulla  oblongata 

'     4th  ventricle 
Superior  medullary  velum 
Corpora  quadrigeraina 


Fig.  180.     Median  section  of  an  adult  human  brain.     (J.  Symington.) 


lateral  ventricles,  the  remains  of  the  first  cerebral  vesicle  receiving  the 
name  of  the  third  ventricle.  The  lower  and  outer  part  of  the  hemi- 
spheres, i.e.  the  part  which  is  first  formed,  becomes  much  thickened 
and  forms  the  corpus  striatum,  which  is  closely  applied  to  the  front 
and  outer  part  of  the  optic  thalamus.  In  the  corpus  striatum  two 
masses  of  grey  matter  are  developed,  namely,  the  nucleus  caudatus 
and  the  nucleus  lenticularis.     A  layer  of  nerve  fibres  ascends  from  the 


THE  STRUCTURE  OF  THE  BRAIX  STEM  411 


C=J,PT 


Ammocojtes 


n^  "t3. 


Teleostea 


Amphibia 


Reptllia 


-Mammalia 


Fig.  181.     Diagrammatic  view  of  the  brain  in  different  classes  of  vertebrates. 

(Gaskell.) 
CB,  cerebellum  ;  pt,  pituitary  body :  pn.  pineal  body ;    c.str,  corpus 
striatum  ;  OHK.  right  <;anglion  habenulne  ;  i.  olfactory  ;  ir,  optic  nerves. 


412 


PHYSIOLOGY 


brain  stem  to  be  distributed  throughout  the  whole  of  the  cerebral  hemi- 
spheres. This  forms  a  sort  of  capsule  to  the  optic  thalamus,  lying  between 
this  body  and  the  corpus  striatum  behind,  but  in  front  piercing  the  corpus 
striatum  between  its  two  nuclei.     It  is  called  the  internal  capsule. 

The  development  of  the  different  parts  of  the  brain  stem  from  the 
three  cerebral  vesicles  and  their  gTadual  subordination  and  over- 
shadowing in  the  course  of  development  by  the  cerebral  hemispheres 
is  well  shown  if  we  compare  the  brain  of  a  fish  with  that  of  a  reptile 
and  again  with  that  of  a  mammal  (Fig.  181).  Man's  position  in  the 
scale  of  animal  life  is  determined,  not  by  increasing  complexity  of  the 
structures  forming  his  brain  stem,  but  by  the  gradual  subordination 


^i.p. 


Fig.  182.  Section  through  the  lower  border  of  the  medulla  oblongata,  at 
the  pyramidal  decussation.  (Bechterew.) 
fla,  anterior  fissure ;  d,  decussation  of  the  pyramids ;  F,  anterior  columns ; 
Ca,  anterior  cornu  ;  cc,  central  canal  ;  S,  lateral  columns ;  fr,  formatio  reti- 
cularis ;  ce,  neck,  and  </,  head  of  the  posterior  cornu  ;  rpGl,  posterior  root 
of  first  cervical  nerve ;  wc,  beginning  of  nucleus  cuneatus ;  ng,  nucleus  gracilis ; 
H^,  funiculus  gracilis  ;  H'^,  funiculus  cuneatus  ;  sip,  posterior  fissure. 

of  these  to  the  latest  formed  cerebral  hemispheres,  and  the  enormous 
growth  of  his  capacity  to  adapt  himself  to  a  varying  environment 
consequent  on  the  increase  in  size  of  his  cerebral  hemispheres. 

THE  HIND-BRAIN 

It  will  be  convenient  to  trace  first  the  modifications  undergone 
by  the  axial  part  of  the  nervous  system  in  the  brain,  and  then  to 
deal  with  the  new  masses  of  grey  matter  which  have  no  homologies  in 
the  spinal  cord,  as  well  as  the  long  tracts  of  white  matter  serving  to 
connect  different  levels  or  different  sides  of  the  brain. 

In  examining  successive  sections  from  the  spinal  cord  up  through 
the  medulla,  the  first  change  which  makes  its  appearance  is  due  to  the 
decussation  of  the  pyramids  (Fig.  182).     Throughout  the  spinal  cord, 


THE  STRUCTURE  OF  THE  BRAIN"  STEM 


il3 


fibres  have  been  crossing  from  one  side  to  the  other  through  the  anterior 
white  cojnmissure,  many  of  them  belonging  to  the  pyramidal  system. 
But  at  the  lower  border  of  the  medulla  we  see  a  large  mass  of  fibres 
crossing  between  the  anterior  columns  and  the  postero-lateral  columns, 
at  first  cutting  off  the  head  of  the  anterior  horn  and  later  on  breaking 
this  up  altogether,  so  that  the  only  definite  collection  of  gi-ey  matter  left 
in  this  situation  is  a  small  part  of  the  lateral  column  of  grey  matter 
known  as  the  lateral  nucleus.  In  this  way  are  formed  the  big  anterior 
columns  of   thermedulla,   which  are  known   as  the   pyramids,  and 


Funiculus  graci 
Funiculus  cuncat  u- 


Sp.  root  of  5th  I 


Formatio  leticulari 


Direct  cerebellai— !}&; 
tract  '\^. 


Lower  end  of  olivary 
eminence 


ile  nucleus 

Cuneate  nucleus 


Subst.cel  Eolandi 


isi?-  Decussation  of  fillet 
'4 


Int.  acces.<  olivary  n 
Nerve  XII. 


Pvniniid 


Fig.  183.     Transverse  section  tlii'ough.  medulla  of  foetus,  immediately  above 
pyramidal  decussation.    (Cunningham.)    Stained  by  Pal-Weigert  method. 


contain  all  the  fibres  that  in  the  cord  are  represented  by  the  direct 
and  crossed  pyramidal  tracts. 

The  next  change  is  due  to  the  ending  of  the  posterior  columns 
(Fig.  183).  These  are  the  central  ascending  branches  of  dorsal  nerve 
roots,  having  therefore  an  origin  outside  the  cord.  On  their  way  up 
the  cord  they  send  in  collaterals  to  end  in  the  grey  matter  of  the 
posterior  horn.  The  main  mass  terminates  in  the  medulla,  just  above 
the  pyramidal  decussation,  in  two  collections  of  grey  matter — the 
nucleus  gracilis  and  the  nucleus  cuneatus — which  are  formed  by  a 
great  hypertrophy  of  the  grey  matter  at  the  root  of  the  posterior 
horn.  The  effect  of  this  development  in  the  dorsal  region  of  the 
medulla  is  to  push  the  head  of  the  posterior  horn  outwards.  At  the 
same  time  this  mass  of  gelatinous  substance  becomes  enlarged,  so  that 
in  section  we  have  three  grey  masses  from  within  outwards,  the  nucleus 
gracilis,  the  nucleus  cuneatus,  and  the  nucleus  of  Rolando. 

The  fibres  of  the  postero-median  column,  which  are  derived 
chiefly  from  the  lower  limb,  end  in  arborisations  round  the  cells  of  the 


414 


PHYSIOLOGY 


nucleus  gracilis,  while  those  of  the  postero- external  column,  or 
column  of  Burdach,  of  which  the  majority  is  formed  by  fibres  from 
the  upper  limbs,  terminate  in  the  grey  matter  of  the  nucleus  cuneatus. 
The  cells  of  these  two  masses  of  grey  matter  of  course  give  off  axons, 
which  can  carry  on  the  impulses  brought  to  them  by  the  fibres  of  the 
posterior  columns.  These  axons  speedily  leave  the  posterior  aspect  of 
the  medulla,  bending  round,  as  the  arcuate  fibres,  to  the  deeper  parts 


I'osterior  longitudinal  fasciculus 

ubstantia  gelatinosa  Rolandi 

inal  root  of  fifth  nerve 
Nucleus  ambiguus 
Ccrobello-olivary  fibres 
M-  Dorsal  accessory  olivary  nucleus 
\nterior  superficial  arcuate  fibres 
Fillet 
Mesial  iccessory  olivary  nucleus 

^  "^S^l    Inferior  olivary  nucleus 


Pyramid 
Arcuate  nucleus 


Anterior  superficial  arcuate  fibres 


Fig.  184.     Transverse  section  through  the  middle  of  the  olivary  region  of 
the  human  medulla.     (Cunningham.) 

of  its  Structure.  Thus  nothing  is  left  to  take  the  place  of  the  posterior 
columns  on  the  posterior  aspect  of  the  cord.  With  the  disappearance 
of  these  columns  and  the  development  of  the  pyramids  we  get  a 
practical  obliteration  of  the  anterior  fissure  and  a  displacement  of  the 
central  canal  towards  the  dorsal  surface.  A  little  higher  up  (Fig.  184) 
the  canal  opens  out  altogether,  forming  the  fourth  ventricle,  covered 
on  its  dorsal  surface  only  by  a  thin  layer  of  ependyma,  a  simple 
epithelium  representing  all  that  is  left  of  the  dorsal  wall  of  the  primitive 
cerebral  vesicle.  The  appearance  of  the  section  is  now  modified  by 
two  structures.  In  the  first  place,  a  new  mass  of  grey  matter,  con- 
sisting of  a  thin  layer  shaped  like  a  flask  with  its  orifice  directed 
inwards,  is  developed  in  the  lateral  part  of  the  medulla,  between  the 


THE  STRUCTURE  OF  THE  BRAIN  STEM  415 

pyramids  in  front  and  the  tubercle  of  Rolando  behind.  This  is  the 
olivary  body,  and  has  on  its  inner  and  dorsal  sides  two  little  grey 
masses  which  are  the  accessory  olivary  bodies.  The  other  feature  is 
the  new  relay  of  sensory  fibres  which  start  from  the  dorsal  nuclei,  the 
nuclei  gracilis  and  cuneatus.  These  fibres  run  outwards  and  forwards 
from  the  nuclei  right  round  the  medulla.  Some  fibres  pass  into  the 
restiform  body  of  the  same  side.  A  larger  number,  forming  the  super- 
ficial arcuate  fibres,  pass  superficially  to  the  olive  to  join  the  restiform 
body  of  the  opposite  side,  while  others,  the  deep  arcuate  fibres,  pass 
deeply  to  the  olives,  and  crossing  in  the  median  raphe  turn  upwards 
in  the  broken  mass  of  grey  and  white  matter  which  lies  between  the 
olives  and  the  superficial  grey  matter  of  the  fourth  ventricle.  This 
decussation,  which  is  known  as  the  '  decussation  of  the  fillet '  or  the 
sensory  decussation,  takes  place  immediately  above  the  level  of 
the  decussation  of  the  pyramids.  In  its  upward  course  it  forms  a 
conspicuous  strand  of  fibres,  lying  close  to  the  mesial  plane  and 
separated  from  its  fellow  of  the  opposite  side  simply  by  the  median 
raphe.  To  this  collection  of  fibres  is  given  the  name  of  the  jillet  or 
lemniscus.  It  is  perhaps  the  most  important  of  the  afferent  tracts 
of  the  brain  stem,  receiving  as  it  does  continuations  of  the  posterior 
columns  of  the  cord  as  well  as  contributions  from  the  various  sensory 
cranial  nerves.  It  may  be  traced  forwards  as  far  as  the  thalamus  and 
subthalamic  region,  where  its  fibres  terminate.  The  region  corre- 
sponding to  the  anterior  column  of  the  spinal  cord  is  thus  invaded  in 
the  medulla  by  two  gxeat  longitudinal  tracts  of  fibres,  namely,  the 
pyramids  and  the  tracts  of  the  fillet.  The  region  corresponding  to  the 
anterior  basis  bundle,  i.e.  that  part  of  the  anterior  columns  occupied 
chiefly  by  intra-spinal  fibres,  is  thus  pushed  further  backwards  and 
finally  comes  to  lie  immediately  beneath  the  grey  matter  of  the  floor 
of  the  fourth  ventricle.  Immediately  dorsally  to  the  fillet  is  to  be 
seen  another  well-marked  bundle  of  longitudinal  fibres,  known  as  the 
posterior  longitudinal  bundle.  These  fibres,  which  serve  to  connect  the 
nuclei  of  many  of  the  cranial  nerves,  can  be  regarded  as  analogous  to 
the  constituent  fibres  of  the  anterior  basis  bundle  in  the  cord,  and  can 
in  fact  be  traced  into  this  part  of  the  anterior  columns  in  the  first 
and  second  cervical  segments  of  the  cord. 

The  anterior  half  of  the  fourth  ventricle  is  covered  in  by  the  cere- 
bellum, which  is  attached  to  the  axial  part  of  the  brain  by  three 
peduncles,  the  inferior  peduncles  or  restiform  bodies,  the  lateral 
peduncles,  which  form  the  great  mass  of  transverse  fibres  known  as 
the  pons  Varolii,  and  the  superior  peduncles,  which  run  forward  to  the 
posterior  corpora  quadrigemina.  The  restiform  bodies  can  be  regarded 
as  the  direct  continuation  forwards  of  the  lateral  columns  of  the  cord, 
minusi\it  pyramidal  tracts,  the  chief  remaining  tract  therefore  being  the 


416  PHYSIOLOGY 

posterior  or  direct  cerebellar  tract.  In  the  region  of  the  dorsal  nuclei, 
however,  it  receives  accession  of  fibres  from  the  gracile  and  cuneate 
nuclei  of  the  same  side  and,  through  the   superficial   arcuate  fibres, 


'est  N. 


:-,'C, 01.  Fibres 


subdel.'Rol.-\-_ 


Fig.  185.     Diagram  to  show  the  sources  of  the  fibres  making  up  the  resti- 

form  body. 
Ar.N,  arcuate   nucleus  ;    Ar  fibres,    arcuate   fibres  ;    Pyr,    pyramid  ; 
C.Sp  Tract,  direct  cerebellar  tract;  C.Ol  fibres,  cerebello-olivary  fibres  ; 
Pl.B,  posterior  longitudinal  bundle;  DN,  nucleus  of  Deiters;  NB,  nucleus 
of  Bechterew  ;   Ro.N,  roof  nuclei ;  Vest.N,  vestibular  nerve. 

from  the  nuclei  of  the  opposite  side,  and  thus  passes  as  a  thick  white 
bundle  into  the  cerebellum.  Among  these  arcuate  fibres  are  also 
a  number  derived  from  the  olivary  body  of  the  opposite  side,  known  as 
the  cerebello-olivary  fibres.  On  its  way  it  is  joined  by  a  smaller 
bundle,  the  '  internal  restiform  body,'  which  conveys  fibres  from 
the  vestibular  division  of  the  eighth  nerve  and  also  serves  to  connect 


THE  STRUCTURE  OF  THE  BRAIN  STEM  417 

Deiters'  nucleus  with  the  cerebellum.     The  restiform  body  is  thus 
made  up  of  the  following  fibres  (Fig.  185)  : 

(1)  The  direct  or  posterior  cerebellar  tract,  derived  from  the  cells 
of  Clarke's  column  oTi  the  same  side  of  the  cord. 

(2)  The    posterior   superficial    arcuate   fibres,    derived   from    the 
gracile  and  cuneate  nuclei  of  the  same  side. 

(3)  The  anterior  superficial  arcuate  fibres,  from  the  gracile  and 
cuneate  nuclei  of  the  opposite  side. 

(4)  The  cerebello- olivary  fibres. 

(5)  The  vestibulo-cerebellar  fibres. 

A  section  through  the  pons  shows  the  fourth  ventricle  widely 
dilated,  with  a  floor  fomied  of  grey  matter  as  in  the  medulla.  The 
chief  difierence  in  the  appearance  of  the  section  is  due  to  the  great 
masses  of  transverse  fibres  which  pass  into  the  pons  by  the  lateral 
peduncles  of  the  cerebellum,  cross  by  the  median  raphe,  and  turn  either 
upwards  or  downwards  on  the  opposite  side  or  end  in  connection 
with  the  nerve-cells  which  are  scattered  throughout  the  white  fibres. 
The  pyramids  can  still  be  seen  as  thick  longitudinal  bundles  on  each 
side  in  the  midst  of  the  transverse  fibres.  They  are  considerably 
larger  than  in  the  medulla  and  become  larger  as  we  trace  them  up 
towards  the  mid-brain,  owing  to  the  presence  of  a  number  of  fibres 
which  are  derived  from  the  cortex  cerebri  and  end  in  the  grey  matter 
of  the  pons.  The  tract  of  the  fillet  lies  on  each  side  of  the  middle 
line  dorsally  to  the  transverse  fibres.  A  little  to  the  outside  of  the 
fillet  is  seen  a  special  mass  of  grey  matter,  known  as  the  superior  olive. 
The  nervous  mass  lying  behind  the  transverse  fibres  of  the  pons, 
})etween  them  and  the  grey  matter  of  the  floor  of  the  fourth  ventricle,  V 
is  known  as  the  formatio  reticularis.  It  is  divided  into  a  lateral  and 
mesial  part  by  the  fibres  of  the  hypoglossal  nerve.  In  the  lateral 
portions  there  is  a  considerable  quantity  of  grey  matter,  which  can  be 
regarded  as  continuous  with  the  grey  matter  of  the  lateral  horns  of  the 
cord.  The  '  lateral  nucleus  '  is  simply  a  condensed  part  of  this  grey 
matter,  lying  between  the  olive  and  the  gelatinous  substance  of  Rolando. 
The  mesial  part  of  the  formatio  reticularis  is  almost  free  of  nerve- 
cells.  The  reticular  appearance  of  this  part  of  the  pons  is  due  to 
the  intersection  of  fibres  which  run  longitudinally  and  transversely.  \. 
The  transverse  fibres  are  a  continuation  of  the  deep  arcuate  fibres. 
The  longitudinal  fibres  in  the  outer  part  of  the  formatio  reticularis  are 
the  representative  of  the  lateral  columns  of  the  cord  after  the  removal 
of  the  direct  cerebellar  and  the  crossed  pyramidal  tracts.  They 
include  therefore  the  antero-lateral  ascending  tract  (tract  of  Gowers) 
and  a  number  of  other  fibres  corresponding  to  the  lateral  basis  bundle 
in  the  cord.  In  the  mesial  part  of  the  formatio  reticuUiris  the  longi- 
tudinal tracts  are  the  tract  of  the  fillet  and  the  posterior  longitudinal 

27 


418  PHYSIOLOGY 

bundle  on  each  side  of  the  middle  line.  In  the  upper  part  of  the  pons 
Varolii  a  well-marked  collection  of  transverse  fibres  are  to  be  seen 
lying  dorsallv  to  the  tracts  of  the  fillet.  This  collection  is  called  the 
corvus  trarezotdes  and  is  made  up  of  ascending -fibres  derived  from 
the  nuclei  of  the  cochlear  nerve,  the  auditory  part  of  the  eighth  nerve. 


^ 


Supr.  ccr.  peduncle 


]U  of  >tlin 


Valve  of  Vieusscns 

Floor  of  4th 
\catricle 


1  01  m.  reticularis 


Sensory  uuchu^  of  )th  ii 
Supr.  olive 


Sensory  root 
of  5th  n.  ijflj 


MidcUcpedunclc 
of  cerebellum 


liansversc  fibres 


Fit-    186      Transverse  seetiuu  through  middle  of  pons  Varolii  of  orang  on  level  of 
■  nuclei  of  fifth  nerve.     (Cunkingham.) 

A  little  further  forward  a  section  will  escape  the  cerebellum  alto- 
crether,  being  bounded  ventrally  by  the  upper  or  anterior  part  of  the 
pons  and  dorsallv  by  a  thin  mass  of  grey  matter,  the  valve  of  Vieussens 
(Fig  186).  On  each  side  of  the  valve  of  Vieussens  may  be  seen  the 
superior  peduncles  of  the  cerebellum.  As  these  peduncles  are  traced 
upwards  they  sink  gi-adually  deeper  into  the  pons  until  they  lie  on  the 
outer  side  of  the  tegmental  region  or  formatio  reticularis.  They  are 
made  up  of  fibres  which  run  from  the  dentate  nucleus  of  grey  matter 
in  the  cerebellum  to  the  mid-brain,  where  they  decussate  below  the 
Sylvian  iter  and  end  in  the  red  nucleus  and  in  the  thalamus  of  the 
opposite  side.    They  also  contain  the  continuation  upwards  of  the 


THE  STRUCTURE  OF  THE  BRAIN  8TEM 


419 


antero-lateral  ascending  tract,  which,  passing  up  in  the  superior 
peduncles,  bends  dorsally  round  the  fourth  nerve  and  then,  turning 
backwards,  ends  in  the  superior  vermis  of  the  cerebellum.  In  a  section 
through  the  upper  part  of  the  pons  the  division  into  the  formatio 
reticularis  or  tegmentum  and  the  part  made  up  of  transverse  and 
longitudinal  fibres,  the  pedal  portion,  is  well  marked  {v.  Fig.  187). 
The  fourth  ventricle  has  now  become  constricted  to  a  narrow  canal 


•Itli  vciitiici 
McstMic.  root  of  5tli  ii 

Postr.  loii.>;.  huridli 

Form,  rcticulari- 
Nucleus  of  lateral  flllot 


5th  nerve 


Valve  of  Vieusscns 

Floor  of  -ith  ventricle 

Supr.  cerebellar 
peduncle 


C  ( iniinencinR.dccus- 
sation  of  supr. 
cerebellar  ped. 

Mesial  flliet 


Pyramids 


Fig.  187.     Section  across  upper  part  of  pons  Varolii  of  tho  orang.     (Cunningham.) 


triangular  in  section  and  closed  above  by  the  valve  of  Vieussens.  It 
is  surrounded,  especially  on  its  ventral  side,  by  grey  matter  containing 
the  cells  of  origin  of  the  fourth  nerve.  In  the  tegmental  portion  we 
may  distinguish  on  each  side  the  superior  cerebellar  peduncle.  Out- 
side the  longitudinal  fibres  of  this  peduncle  are  a  number  of  transverse 
fibres  derived  from  the  corpus  trapezoides  seen  in  the  previous  section. 
To  these  fibres  is  given  the  name  of  the  '  lateral  fillet.'  They  are  on 
their  way  to  end  in  the  roof  of  the  mid-brain  in  the  posterior  corpora 
quadrigemina.  The  posterior  longitudinal  bundle  lies  near  the 
middle  line,  innnediately  under  the  grey  matter  of  the  floor  of  the 
fourth  ventricle,  while  the  longitudinal  fibres  of  the  fillet,  now  called 
the  mesial  fillet,  form  a  distinct  mass  in  the  ventral  portion  of  the 
formatio  reticularis.  The  pedal  portion  contains  the  longitudinal 
fibres  of  the  pyramids,  now  much  increased  in  amount,  cut  up  into 
bundles  by  transverse  fibres  derived  from  the  middle  peduncles  of  the 
cerebellum. 

The  cerebellum,  which  covers  in  the  fore  part  of  the  fourth  ventricle, 


420 


PHYSIOLOGY 


will  have  to  be  described  in  greater  detail  later  on.  At  present  it 
will  suffice  to  say  that  it  consists  of  a  middle  and  two  lateral  lobes. 
The  surface  of  the  middle  lobe  turned  towards  the  fourth  ventricle  is 
known  as  the  inferior  vermis,  the  dorsal  surface  forming  the  superior 
vermis.  Each  vermis  and  each  lateral  lobe  is  subdivided  into  a 
number  of  smaller  lobes.     The  intimate  structure  of  all  parts  of  the 


Inf.  corpus  quadrigeminum 

Mesenc.  root  of  5th  n. 
Nucleus  of  4th  nerve 
Inf.  brachiuni 

long,  bundle 

Mesial  fillet 


Grey  matter 


Aqueduct  of. 
Sylvius 


I 


Fig. 


Crust  a 


188,     Transverse  section  through  human  mid-bram,  on  level  of  the 
inferior  corpora  quadrigeniina.     (Cunningham.) 


cerebellum  is,  however,  very  uniform.  It  consists  of  a  mass  of  white 
matter  internally,  covered  by  a  layer  of  grey  matter,  the  extent 
of  grey  matter  being  largely  increased  by  the  formation  of  numerous 
parallel  and  more  or  less  curved  grooves  or  sulci  which  give  the  whole 
organ  a  laminate  appearance.  In  the  mass  of  white  matter,  which 
forms  the  core  of  each  lateral  hemisphere,  is  an  isolated  nucleus  of 
grey  matter  known  as  the  corpus  dentatum.  In  the  white  matter  of 
the  middle  lobe  is  another  mass  of  grey  matter  known  as  the  roof 
nucleus  or  nucleus  fastigii.  Between  the  nucleus  fastigii  and  the 
nucleus  dentatum  are  two  other  nuclei,  the  nucleus  globosus  and  the 
nucleus  emboliformis. 


THE  STRUCTURE  OF  THE  BRAIN  STEM 


421 


THE  MID-BRAIN 

A  little  further  forward  the  fourth  ventricle  comes  to  an  end,  and 

the  section  passes  through  the  mid-brain  (Fig.  188),  the  cavity  of  the 

second   cerebral   vesicle   being  represented  by  the   narrow   Sylvian 

aqueduct,  bounded  dorsally  by  the  corpora  quadrigemina  and  ventrally 

Superior  quadri- 
gcminal  body 


Extl.  gen.  body 
Infr.  braeliiuin 
Intl.  gen.  body 

Mesial  fillet 
Cnista 
iptie  tract 


Fig.  189.     Tran.sverse  section  through  human  mid-brain  at  the  level  of  the  superior 
corpus  quadrigeminum.     (Cunningham.) 

by  the  crura,  the  stalks  of  the  brain.  The  crura  are  divided  by  an 
irregular  mass  of  grey  matter,  the.  substantia  nigra,  into  two  parts. 
The  ventral  portion  is  known  as  the  fes  or  crusta.  It  is  composed 
almost  entirely  of  longitudinal  white  fibres,  among  which  is  the 
continuation  forwards  of  the  pyramids  of  the  medulla.  The  pyramids, 
however,  form  only  about  two-fifths  of  the  total  mass  of  white  fibres, 
the  rest  consisting  of  fibres  which  run  from  the  different  parts  of  the 
cerebral  cortex,  especially  from  the  frontal  and  temporal  lobes,  to  end 
in  the  formatio  reticularis  of  the  pons,  probably  in  relation  with  the 
grey  matter  in  this  situation  and  with  the  endings  of  the  transvei*se 
fibres  derived  from  the  cerebellum  and  forming  the  middle  pedunclea 


422  PHYSIOLOGY 

of  the  cerebellum.  The  dorsal  part,  the  tegmentum,  is  a  direct  pro- 
longation forwards  of  the  formatio  reticularis  of  the  medulla  and  pons, 
and  like  this  contains  much  scattered  grey  matter.  On  a  level  with  the 
inferior  corpora  quadrigemina  a  number  of  decussating  fibres  are  to 
be  seen  in  the  tegmentum,  w^hich  are  derived  from  the  superior  cere- 
bellar peduncles.  Their  decussation  is  complete  at  the  level  of  the 
upper  border  of  the  inferior  corpora  quadrigemina.  Here  each 
peduncle  turns  upwards,  and  a  large  proportion  of  its  fibres  end  in  the 
red  mtcleus  (Fig.  189),  a  mass  of  grey  matter  forming  a  conspicuous 
feature  of  sections  through  the  anterior  part  of  the  mid-brain.  Many 
of  the  fibres  pass  round  the  red  nucleus,  forming  a  sort  of  capsule 
over  it,  to  the  ventral  part  of  the  optic  thalamus,  in  which  they 
probably  end.  It  is  possible  that  a  certain  proportion  pass  through 
the  optic  thalamus  and  run  straight  to  the  cerebral  cortex  of  the 
Rolandic  area.  The  lateral  fillet  has  disappeared  from  the  region  of 
the  tegmentum  and  passed  into  the  inferior  corpora  quadrigemina. 
The  mesial  fillet  forms  a  flat  band  lying  to  the  outer  side  of  the  red 
nucleus  and  comes  into  close  relation  with  a  ganglion  of  the  fore-brain, 
known  as  the  internal  geniculate  body.  The  roof  of  the  mid-brain  is 
formed  by  the  corpora  quadrigemina.  The  inferior  corpora  quadri- 
gemina are  composed  of  central  grey  matter  encapsulated  by  white 
matter,  derived  chiefly  from  the  lateral  fillet.  The  superior  corpora 
quadrigemina  are  composed  of  several  layers  of  grey  matter  traverneo 
by  nerve  fibres,  derived  partly  from  the  fillet,  partly  from  the  optic 
tract,  and  partly  from  the  occipital  lobe  of  the  cerebral  hemisphere. 

THE  FORE-BRAIN 
In  the  fore-brain  the  most  important  feature  is  the  optic  thalami, 
the  two  head  ganglionic  masses  of  the  brain  stem  (Fig.  190).  In  this 
region  the  central  neural  canal,  which  in  the  mid-brain  forms  the 
Sylvian  iter,  widens  out  to  the  third  ventricle,  in  the  lateral  walls  of 
which  are  developed  the  two  optic  thalami.  It  is  a  narrow  cleft, 
rapidly  deepening  in  depth  from  behind  forwards.  As  we  trace 
sections  forwards  we  see  that  the  two  crura  cerebri  diverge  from  one 
another.  The  floor  of  the  third  ventricle  is  thus  left  thin.  It  is  formed 
from  behind  forwards  by  a  thin  layer  of  grey  matter  with  numerous 
vessels,  the  locus  ferforatus  posticus,  two  small  eminences,  the  corpora 
mammillaria,  and  in  front  of  these  another  lamina  of  grey  matter 
known  as  the  tuher  cinereum.  In  front  of  the  tuber  cinereum  is  the 
infundihulum,  which  leads  to  the  posterior  lobe  of  the  pituitary  body. 
In  front  of  the  infundibuluni  the  optic  chiasma  is  closely  attached  to 
the  lowest  part  of  the  anterior  wall  of  the  ventricle.  The  front  wall  is 
formed  by  a  thin  layer  of  nervous  matter,  the  lamina  cinerea,  at  the 
upper  border  of  which,  projecting  slightly  into  the  ventricle,  is  a 


THE  STRUCTURE  OF  THE  BRAIN  STEM  423 

strand  of  white  fibres  connecting  the  anterior  parts  of  the  two  optic 
thalami  and  known  as  the  anterior  commissure.  The  roof  of  the 
third  ventricle  is  formed  entirely  of  epithelium,  the  ependyma,  alonj,' 
the  upper  surface  of  which  is  the  layer  of  pia  mater,  the  velum  mter- 


Cor|jUH  callosuir. 
Lateral  ventricle 
Nucleus  caudatus 

Internal  capsule 

Thalamus 
Nucleus  lentifornii? 

Anterior  commis- 
sure 


Colliculus  superior ^— y- 

Inferior  brachium 1^ 

Colliculus  inferior 


4th  nerv 

jCrigonum  lemnisci 
5th  nerve 
;^rachium  con- 
junctivum 

Pons 


8th  nerve 

Restiform  body 

9th  nerve 

10th  nerve 

01  iv 


Olfactory  tract 
Trigonum  olfac. 


Flc.   190.     Right  lateral  aspect    of    brain   stem,   with  a  part   of  the 
cerebnim.     (J.  SYMiNfJoy.) 

positum.  The  roof  is  invajiinated  into  the  cavity  by  two  delicate 
vascular  fringes,  the  choroid  plexmes.  At  the  back  part  of  the  roof  is 
attached  the  stalk  of  the  pineal  body,  and  behind  this  stalk,  between 
the  anterior  parts  of  the  anterior  corpora  quadrigemina.  is  a  small 
space  known  as  the  trigonum  Iwhenulce,  which  contains  a  well-marked 
collection  of  nerve-cells  known  as  the  (jamjlion  hahenulw.  The  lateral 
walls  are  formed  entirely  by  the  optic  thahuni.  The  upper  surface  of 
the  optic  thalamus  looks  into  the  lateral  ventricle  of  the  cerebral 


424 


PHYSIOLOGY 


hemispheres,  from  which  it  is  separated  by  the  velum  interpositum 
and  by  the  ependyma,  the  epithelium  completing  the  inferior  wall  of 
the  lateral  ventricle  in  this  region.  It  consists  of  three  masses  of 
grey  matter — -the  anterior  nucleus,  the  lateral  nucleus  (the  largest 
of  the  three),  and  the  mesial  nucleus.  Its  outer  surface  is  in  contact 
with  the  layer  of  nerve  fibres  formed  by  the  crusta  of  each  crus  cerebri 
as  it  diverges  from  its  fellow  to  pass  up  into  the  cerebral  hemispheres. 
Into  this  layer,  '  the  internal  capsule,'  fibres  proceed  from  all 
parts  of  the  thalamus  to  pass  to  the  cerebral  cortex.     The  anterior 


nm 


Fio.  191.  Transverse  section  through  upper  part  of  mid-bram. 
Th,  thalamiis  ;  hrs,  brachium  superior  ;  cqs,  anterior  (or  superior)  corpus 
quadrigeniinum  ;  cgi,  cqe,  internal  and  external  geniculate  bodies  ;  /,  fillet ; 
s,  aqueduct ;  pi,  posterior  longitudinal  bundle  ;  r,  raphe  ;  ///,  third  nerve  ; 
nlll,  its  nucleus  ;  Ipp,  posterior  perforated  space  ;  sn,  substantia  nigra  ; 
cr,  crusta ;  //,  optic  tract  ;  M,  medullary  centre  of  the  hemisphere ; 
nc,  nucknis  caudatus  ;  si,  stria  terminalis. 


extremity  of  the  thalamus,  known  as  the  anterior  tubercle,  forms  a 
marked  projection  into  tlie  lateral  ventricle.  In  front  of  this,  the 
foramen  of  Monro  leads  from  the  third  ventricle  into  the  lateral 
ventricle.  This  foramen  is  bounded  anteriorly  by  a  strand  of  fibres, 
known  as  the  '  anterior  pillar  of  the  fornix,'  which  lies  just  behind  the 
anterior  commissure  and  forms  a  conspicuous  feature  in  the  anterior 
part  of  the  lateral  wall  of  the  third  ventricle.  It  passes  in  the  wall 
down  to  the  corpus  mammillare.  From  the  corpus  mammillare  a 
well-marked  bundle  of  fibres  passes  up  into  the  optic  thalamus  to  end 
round  the  large  cells  in  the  anterior  nucleus  of  the  thalamus.  The 
posterior  extremity  of  the  thalamus  forms  a  definite  prominence, 
the  j)ulvinar.     To  the  outer  and  back  part  of  the  pulvinar  two  bodies 


THE  STRUCTUEE  OF  THE  BRAIN  STEM  425 

are  developed,  known  as  the  geniculate  bodies.  These  may  be  regarded 
as  special  outgrowths  of  the  grey  matter  of  the  optic  thalamus,  one  of 
which,  the  external  geniculate  body,  is  in  close  connection  with  the 
fibres  from  the  optic  tracts,  w^hile  the  other,  the  internal  geniculate  v 
body,  receives  fibres  from  the  lateral  fillet  ultimately  derived  from 
the  organ  of  hearing.  In  a  section  through  the  fore  part  of  the  mid- 
brain (Fig.  191)  these  two  bodies  may  be  seen  lying  to  the  outer  . 
side  of  the  anterior  corpora  quadrigemina,  so  that  the  fore-brain,  to 
a  certain  extent,  enfolds  the  anterior  part  of  the  mid-brain.  Below 
the  thalamus  at  its  back  part  is  the  prolongation  forwards  of  the  teg- 
mentum of  the  crus.  This  is  often  spoken  of  as  the  subthalamic 
region.  The  red  nucleus  is  a  conspicuous  object  in  sections  through 
the  back  part  of  this  region,  but  gradually  diminishes  as  we  proceed 
forwards,  and  disappears  before  the  level  of  the  corpora  mammil- 
laria  is  reached.  The  mesial  fillet,  which  in  the  mid-brain  lies  on  the 
lateral  and  dorsal  aspect  of  the  red  nucleus,  is  prolonged  upwards 
together  with  fibres  from  the  superior  cerebellar  peduncle  into  the  ' 
ventral  part  of  the  thalamus,  where  probably  all  of  the  fibres  end  in 
connection  with  the  thalamic  cells.  The  substantia  nigra  gradually 
disappears.  Before  it  has  disappeared  we  may  see  on  its  outer  side 
a  special  collection  of  grey  matter  called  the  nucleus  of  Luys  or  the 
corpus  subthalamicum.  In  addition  to  the  anterior  and  posterior 
commissures  already  described  as  connecting  the  two  optic  thalami 
at  the  front  and  back  of  the  third  ventricle,  the  two  sides  are  con- 
nected about  the  middle  of  the  cavity  by  the  middle  or  soft  commis- 
sure. The  optic  thalamus  is  often  described  together  with  the  corpus  / 
striatum  as  forming  the  basal  ganglia.  The  corpus  striatum  is, 
however,  genetically,  and  probably  functionally,  part  of  the  cerebral 
hemispheres,  and  its  connections  will  therefore  be  best  dealt  with 
when  describing  the  latter  bodies. 

THE  AXIAL  GREY  MATTER 
In  the  spinal  cord  we  could  distinguish  between  the  anterior  grey 
matter  giving  origin  to  the  motor  iierves,  the  posterior  grey  matter 
serving  as  an  end  station  for  a  number  of  the  sensory  posterior  root 
fibres,  and  a  lateral  horn,  less  well  marked,  probably  giving  origin 
to  the  visceral  system  of  nerves.  As  the  central  canal  widens  out  to 
form  the  fourth  ventricle,  the  relative  position  of  these  various  parts 
becomes  altered,  the  anterior  grey  matter  being  now  nearest  the 
median  line,  while  the  posterior  grey  matter  lies  more  laterally.  Part 
of  the  lateral  giey  matter  seems  to  lie  deeper  than  the  rest,  from 
w^hich  it  is  separated  by  the  tangle  of  fibres  and  cells  known  as  the 
formatio  reticularis.  All  the  cranial  nerves  from  the  third  to  the 
twelfth  arise  or  end  in  the  axial  grey  matter,  or  in  close  proximity 


426  PHYSIOLOGY 

to  it.  So  great,  however,  is  the  complexity  of  this  part  of  the  nervous 
system,  and  so  involved  are  the  genetic  relations  of  the  various  nerves, 
that  it  is  difficult  or  impossible  in  many  cases  to  state  definitely  the 
spinal  analogies  of  the  various  nerves. 

The  cranial  nuclei  (of  origin  or  termination)  may  be  roughly  classed 
as  follows  : 

(1)  Motor  Somatic  Nuclei.  These  consist  of  an  almost  continuous 
column  of  nmltipolar  cells,  lying  close  to  the  middle  line  on  each  side 

DESCENDING 


NUCLEUS 


Fig.  192.     Cross-section  of  medulla  showing  niiclei  of  nerves  X  and  xii. 

(Cunningham.) 

in  the  floor  of  the  fourth  ventricle,  the  Sylvian  iter,  and  the  back 
part  of  the  third  ventricle.  From  below  upwards  these  groups  of  cells 
give  origin  to  the  fibres  of  : 

(a)  The  hypoglossal  nerve. 

(6)  The  sixth  nerve. 

(c)  The  fourth  nerve. 

[d)  The  third  or  oculo-motor  nerve. 

(2)  Splanchnic  Sensory  Nuclei.  Immediately  outside  the  column 
of  motor  cells  is  a  column  of  grey  matter  which  receives  the  termina- 
tions of  the  afferent  fibres  belonging  to  the  ninth,  tenth,  and  eleventh 
nerves,  and  is  sometimes  called  the  vago-glossopharyngeal-accessory 
nucleus.  This  grey  matter  of  course  does  not  give  rise  to  the  fibres 
of  these  nerves,  which,  like  other  sensory  nerves,  are  axons  of  ganglion- 
cells  lying  outside  the  central  nervous  system. 


THE  STRUCTURE  OF  THE  BRAIN  STEM 


427 


(3)  Splanchnic  Motor  Nuclei.  These  lie  more  deeply  at  some 
distance  from  the  middle  line,  and  include  the  nucleus  ambiguus  for 
the  efferent  fibres  of  the  vago-glossopharyngeal,  the  nucleus  of  the 
seventh   or   facial   nerve    (originally   splanchnic   or   branchial,    now 


Fig.  193.  Diagram  showing  tlic  biain  couuections  of  the  vagus,  glosso- 
pharyngeal, auditory,  facial,  abducent,  and  trigeminal  nerves.  (Cun- 
ningham after  Obeksteinek.) 


typically  somatic),  and  the  motor  nucleus  of  the  fifth  nerve  with  its 
prolongation  into  the  mid-brain. 

(4)  Sensory  Somatic  Nuclei.  The  chief  representative  of  this  group 
is  the  great  sensory  root  of  the  fifth  nerve.  The  fibres  of  this  nerve 
arise  from  the  Gasserian  ganglion,  pierce  the  fibres  of  the  pons  Varolii, 
and  run  to  the  dorso-lateral  part  of  the  pons,  where  they  divide  into 
ascending  and  descending  fibres.  These  fibres  form  a  cap  to  the 
substantia  gelatinosa,  the  descending  branches,  which  are  longer, 
being  conspicuous  in  sections  of  the  medulla  as  low  down  as  the  first 


428  PHYSIOLOGY 

or  second  cervical  nerve.     This  nerve  gives  common  sensation  to 
practically  the  whole  of  the  head. 

It  is  doubtful  in  what  group  we  should  place  the  fibres  of  the  eighth 
nerve.  This  nerve  really  consists  of  two  parts  very  different  in  func- 
tion, the  cochlear  or  auditory  nerve,  and  the  vestibular  or  labyrinthine 
nerve.  The  fibres  of  each  are  derived  from  ganglion-cells  in  the 
internal  ear,  pass  to  the  medulla  at  its  widest  part,  and  then,  dividing 


FIBRES  TO  NUCL  LEMNISCI 
&CORPORA  QUADRIGEMINA 


NERVE-ENDINGS 

iN  ORGAN  OF  CORTl 

Fig.  194.  Plan  of  the  course  and  connections  of  the  fibres  forming  the 
cochlear  root  of  the  auditory  nerve.  (Schafer.) 
r,  restif oriu  body ;  V,  descending  root  of  the  fifth  nerve  ;  tub.ac,  tuberculum 
acusticum  ;  n.acc,  accessory  nucleus  ;  so,  superior  olive  ;  n.tr,  nucleus 
of  trapezium  ;  n.  VI,  nucleus  of  sixth  nerve ;  VI,  issuing  root-fibre  of  sixth 
nerve. 


into  two,  terminate  in  masses  of  grey  matter  situated  at  the  extreme 
lateral  part  of  the  floor  of  the  fourth  ventricle. 

The  branches  of  the  cochlear  nerve  (Fig.  194)  make  connection 
with  two  collections  of  cells,  the  dorsal  nucleus,  apparently  embedded 
in  the  fibres  of  the  root  itself,  and  the  accessory  nucleus,  a  little  trian- 
gular mass  of  grey  matter  situated  in  the  angle  between  the  cochlear 
and  vestibular  nerves.  From  these  nuclei  fibres  are  given  off  which 
take  two  courses.  Some,  following  the  previous  course  of  the  cochlear 
nerve,  pass  across  the  surface  of  the  fourth  ventricle  as  the  strice 
medullares  or  stricB  acousticce,  and  then  bending  inwards  pass  into 
the  tegmentum  of  the  opposite  side.  Others  pass  deeply  and  form 
a  mass  of  transverse  fibres  in  the  ventral  part  of  the  tegmentum,  the 
corpus  trapezoides  or  tra'pezium.  After  making  connections  with  the 
superior  olivary  body  and  a  special  nucleus,  they  join  the  superficial 
set  of  fibres,  and  run  up  in  the  tegmentum  to  the  inferior  corpora 
quadrigemina,  forming  the  lateral  fillet. 


THE  STRUCTURE  OF  THE  BRAIX  STEM  429 

The  vestibular  nerve  (Fig.  195)  also  has  two  nuclei  of  termination, 
the  median  nucleus  with  small  cells,  and  the  lateral  or  Betters^  nucleus 
with  large  cells.  Some  fibres  pass  also  to  the  nucleus  of  Bechierew, 
which  is  in  close  relation  with  the  roof  nuclei  of  the  cerebellum.  The 
descending  fibres  end  chiefly  in  the  median  nucleus,  while  the  ascending 
fibres  end  in  Deiters'  nucleus.  From  the  latter  a  distinct  band  of 
fibres  passes  up  to  the  cerebellum,  forming  the  median  division  of  the 


TO  VERMIS 


/.<* 


FIBRES    O 

VESTIBULA 

ROOT 


NERVE      -y/Vf/^GANGLION   OF 
ENDINGS       ^/''^  SCARPA 
IN  MACUI->E    ''■ 
8.  AMPULL/E 


Fig.  19.5.  Plan  of  the  course  and  connections  of  the  fibres  forming  the 
vestibular  root  of  the  auditory  nerve.  (Schaf£b.) 
r,  restiform  body  ;  v,  descending  root  of  fifth  nerve  ;  p,  cells  of  principal 
nucleus  of  vestibular  root ;  d,  fibres  of  descending  vestibular  root ;  nd,  a  cell 
of  the  descending  vestibular  nucleus  ;  d,  cells  of  nucleus  of  Deiters  ;  B,  cells 
of  nucleus  of  Bechterew  ;  nt,  cells  of  nucleus  tecti  (fastigii)  of  the  cere 
bellum ;  plb,  fibres  of  posterior  longitudinal  bxindle.  No  attempt  has  been 
made  in  this  diagram  to  represent  the  actual  positions  of  the  several  nuclei. 
Thus  a  large  part  of  Deiters'  nucleus  lies  dorsal  to  and  in  the  immediate 
vicinity  of  the  restiform  body. 


restiform  body,  while  other  fibres  run  across  to  the  tegmentum  of  the 
opposite  side,  where  they  take  part  in  the  formation  of  the  posterior 
longitudinal  bundle. 

In  a  section  through  the  fourth  ventricle  through  the  middle  of 
the  pons,  a  group  of  large  cells  is  seen  in  the  position  occupied  by  the 
nucleus  of  the  hypoglossal  below.  These  cells  give  rise  to  the  fibres 
of  the  sixth  nerve.  Another  group  is  seen  lying  laterally  and  more 
deeply,  evidently  belonging  to  the  lateral  horn  system.  This  is  the 
nucleus  of  tlie  seventh  or  facial  nerve,  the  fibres  of  which  pass  dorsally 
and  anteriorly,  looping  round  the  sixth  nerve-nucleus,  before  issuing 
as  the  root  of  the  seventh  nerve. 


430 


PHYSIOLOGY 


In  the  upper  part  of  the  pons  we  find  the  fifth  nerve  (Fig.  196)  with 
its  two  roots.     The  fibres  of  the  sensory  root  derived  from  the  cells  of 

the  Gasserian  ganglion  bifurcate.  The 
upper  divisions,  which  are  short,  end 
ill  a  mass  of  grey  matter  at  the 
lateral  part  of  the  formatio  reticularis, 
the  so-called  sensory  root,  while  the 
descending  divisions  form  a  long  strand 
of  white  fibres  passing  down  as  far 
as  the  second  cervical  nerve  and  lying 
over  the  substantia  gelatinosa  of 
Eolando,  around  the  small  cells  of 
which  the  fibres  finally  terminate. 
The  motor  fibres  arise  partly  from  the 
motor  nucleus,  a  mass  of  cells  lying 
internally  to  the  sensory  nucleus,  and 
belonging  probably  to  the  lateral 
horn  system.  A  large  number  are 
derived  from  a  long  column  of  cells, 
which  stretches  forward  from  the 
nucleus  as  far  as  the  level  of  the 
anterior  corpora  quadrigemina.  These 
fibres  are  known  as  the  descending 
motor  root  of  the  fifth  nerve. 

In  the  region  of  the  mid-brain, 
besides  the  root  of  the  fifth  nerve 
just  mentioned,  we  find  only  the 
motor  nuclei  of  the  third  and  fourth 
nerves,  which  are  situated  near  the 
median  line  in  the  ventral  part  of  the 
central  grey  matter,  corresponding  in 
situation  to  the  sixth  and  twelfth 
nerves  lower  down. 


Fig.  196.  Diagram  showing  cen- 
tral connections  of  fifth  nerve. 
(Cajal.) 

A,  Gasserian  ganglion ;  B,  acces- 
sory motor  nucleus  ;  c,  main 
motor  nxidciis ;  n,  facial  nucleiis ; 
K,    nucleus  of   hypoglossal; 

F,  sensory  nucleus  of  fifth  nerve; 

G,  cerebral  tract  (fillet)  of  fifth 
nerve. 


INTERMEDIATE  GREY  MATTER  OF  THE  CEREBRAL    AXIS 

The  masses  of  grey  matter  which  are  found  throughout  this  region 
may  be  regarded  as  extra  shunting  stations  (or  association  centres 
for  various  systems  of  nuclei  and  conducting  paths),  which  have 
arisen  in  consequence  of  the  great  complexity  of  reaction  required  of 
the  nerve  mechanisms  in  connection  with  the  organs  of  special  sense. 
We  must  confine  ourselves  here  to  little  more  than  the  enumeration 
of  the  chief  masses,  though  we  shall  have  occasion  to  refer  to  some  in 
more  detail  when  dealing  with  the  co-ordinating  mechanisms  of  the 


THE  STRUCTURE  OF  THE  BRAIN  STEM  431 

cerebral  axis.     From  below  upwards  we  may  enumerate  the  followinp: 
grey  masses  : 

In  the  medulla  is  the  large  olivary  body,  with  the  accessory  olive 
lying  on  its  inner  side.  Each  olive  sends  fibres  across  the  middle  line 
to  the  opposite  cerebellar  hemisphere,  and  must  be  regarded  as  con- 
nected with  this  body  in  its  functions,  since  atrophy  or  removal  of  one 
side  of  the  cerebellum  is  followed  by  atrophy  of  the  opposite  olive. 

In  the  pons  we  find  a  similar  but  smaller  body,  the  superior  olive, 
in  the  neighbourhood  of  the  nucleus  of  the  seventh  nerve.  The  superior 
olive  is  closely  connected  with  the  co-ordination  of  visual  and  vestibular 
impressions  with  the  eye  movements. 

Deiters'  nucleus,  which  occurs  in  the  same  region,  although  described 
as  one  of  the  nuclei  of  the  eighth  nerve,  might  equally  well  be  included 
in  this  class  owing  to  its  manifold  connections  with  both  afferent  and 
efferent  mechanisms. 

In  close  connection  with  Deiters'  nucleus  are  a  number  of  grey 
masses  in  the  cerebellum,  the  roof  nuclei  in  the  roof  of  the  fourth 
ventricle. 

In  the  mid-brain  we  must  mention  the  superficial  grey  matter 
covering  the  corpora  quadrigemina. 

On  the  ventral  side  of  the  Sylvian  iter  are  the  various  masses  of 
grey  matter  in  the  crura,  the  red  nucleus,  a  large  mass  in  the  tegmentum 
just  below  the  oculo-motor  nucleus,  and  the  suhstantia  nigra,  which 
divides  each  crus  into  two  parts,  the  dorsal  tegmentum  and  the  ventral 
pes  or  crusta. 

Finally  at  the  fore  part  of  the  cerebral  axis  we  come  to  the  great 
ganghonic  mass  already  described,  the  optic  thalamus  and  the  geniculate 
bodies.  The  geniculate  bodies  may  be  regarded  as  outgi'owths  of  the 
optic  thalamus  which  have  developed  in  connection  with  the  termina-  \ 
tions  of  the  auditory  and  the  optic  nerve  fibres.  The  optic  thalamus 
is  connected  by  fibres  with  all  parts  of  the  cortex  and  represents  the 
termination  of  the  whole  tegmental  system,  so  that  in  many  ways  it 
may  be  regarded  as  a  sort  of  foreman  of  the  central  nervous  system, 
controlling  the  activities  of  the  lower  level  centres  and  bringing  all  parts 
of  this  system  in  relation  with  the  su|>reme  cerebral  cortex. 

THE  CHIEF  LONG  PATHS  IN  THE  BRAIN  STEM 
In  dealing  with  the  spinal  cord  we  were  able  to  treat  it  as  one 
organ,  very  largely  on  account  of  the  uniformity  of  the  afferent  and 
efferent  mechanisms  connected  with  its  various  segments.  Every 
afferent  impulse  arriving  at  the  cord  has  many  possible  paths  open  to 
it,  on  account  of  the  branching  of  the  nerve  fibres  as  they  enter  the  cord 
and  the  connection  of  these  branches  with  different  neurons  of  varying 
destination.     The  exact  path  taken   by  any  given   impuL>e   under 


432  PHYSIOLOGY 

any  given  set  of  circumstances  is  determined  by  the  varying  resistance 
at  the  synapses  which  intervene  between  the  terminations  of  the 
afferent  fibres  conveying  the  impulse  and  the  next  relay  of  neurons. 
These  resistances  in  their  turn  are  altered  by  the  processes  of  facilita- 
tion and  inhibition,  which  may  be  due  to  contemporaneous  or  previous 
events.  A  conspicuous  example  of  these  conditions  is  afforded  by 
the  phenomena  of  simultaneous  and  successive  spinal  induction. 

The  uniformity  of  afferent  and  efferent  mechanisms  disappears 
when  we  include  the  brain  stem  with  the  spinal  cord.     The  main 
efferent  channel   of  impulses  is  still  through  the  spinal  cord,  since 
here  are  found  the  efferent  mechanisms  for  all  the  skeletal  muscles 
of  the  trunk  and  limbs,  the  chief  servants  of  the  central  nervous 
system  in  the  daily  events  of  life.     Other  efferent  channels  are  added, 
which  acquire  special  importance  with  the  growth  of  the  upper  brain  or 
cerebral  hemispheres.     These  mechanisms  include  those  for  the  move- 
ments of  the  eye  muscles,  those  concerned  in  facial  expression,  and  those 
responsible  for  the  movements  of  the  mouth  in  mastication  and 
deglutition,    and   in   man,    in   speech.     Important   visceral   efferent 
fibres  are  also  contained  in  the  vago-glossopharyngeal  nerves,  which 
leave  the  brain  stem  at  its  hindmost  part  in  the  region  of  the  medulla 
oblongata,  and  influence  the  condition  of  the  heart  and  the  alimentary 
canal  with  its  accessory  organs.     On  the  other  hand,  the  afferent 
mechanisms  of  the  brain  stem  far  transcend  in  importance,  i.e.  in  their 
influence  on  the  reactions  of  the  animal,  those  of  the  spinal  cord. 
Among  these  afferent  mechanisms  are  those  which  we  have  spoken  of 
as  '  projicient '  sense  organs  or  organs  of  foresight,  the  impulses  from 
which  must  predominate  over  all  reactions  determined  by  the  immediate 
environment  of  the  animal.     Into  the  medulla  oblongata  are  poured 
,the  impulses  from  the  greater  part  of  the  alimentary  canal  and  from 
the  heart  (the  chief  factor  in  the  circulation)  and  the  lungs.     At  the 
junction  of  the  medulla  and  pons  is  the  great  eighth  nerve,  really 
consisting  of  two,  one  of  which,  the  cochlear  nerve,  carries  impulses 
from  the  projicient  sense-organ  of  hearing,  while  the  other,  the  vesti- 
bular nerve,  has  its  terminations  in  the  labyrinth,  the  sense-organ  of 
equilibration.     To  the  impressions  received  from  this  organ  all  the 
complex  co-ordinating  motor  mechanisms  of  the  spinal  cord  have  to  be 
subordinated,  in  order  that  they  may  co-operate  in  the  maintenance 
of  the  equilibrium  of  the  body  as  a  whole.     Into  the  pons  enters  the 
fifth  nerve,  carrying  sensory  impressions  from  the  whole  of  the  head, 
while  in  the  mid-  and  fore-brain  we  find  the  endings  of  the  optic 
tracts  derived  from  the  eyes  and  carrying  visual  impressions.     From 
the  front  of  the  fore-brain  are  produced  the  olfactory  lobes. 

At  each  segment  or  level  in  the  brain  stem  the  afferent  fibres  from 
these  various  sense-organs  enter  and  join  afferent  tracts,  carrying 


THE  STRUCTURE  OF  THE  BRAIN  STEM  433 

impulses  on  from  the  spinal  cord — impulses  originally  derived  from  the 
muscles  and  skin  of  the  trunk  and  limbs.  At  each  level  there  may 
be  an  immediate  '  reflection  '  back  to  the  cord,  so  that  the  spinal 
afferent  impressions  may  co-operate  with  the  cranial  afferent  impres- 
sions in  the  production,  through  the  spinal  cord,  of  reactions  affecting 
the  viscera  or  the  skeletal  muscles.  On  the  other  hand,  both  kinds  of 
afferent  impressions  may  pass  on  up  the  brain  stem  to  involve  higher 
centres,  and,  mingling  with  impulses  from  other  afferent  nerves  or  from 
the  projicient  sense-organs,  may  result  at  some  higher  level  in  an  efferent 
discharge,  which  may  include  reactions  not  represented  in  the  cord, 
or  reactions  of  far  greater  complexity  than 
are  possible  in  the  purely  spinal  animal. 

In   consequence   of    the   endless  complex 
intermingling  of  afferent  impulses,  any  dia- 
grammatic representation  of  tracts  is  apt  to 
be  misleading,  unless  it  be  remembered  that 
at   each   break  or  synapse   in  the  chain  of 
neurons  there  are   numerous  possibilities   of 
branching  discharge,  and  that  in 
our  diagrams  we  can  only  give 
the  course  of  such  impulses  as, 
by   the    frequency  of   repetition 
in  the  average  life  of  the  animal, 
have  involved  the  grouping  of  a 
large  number  of  nerve  paths  of 

similar  function  into  tracts.  The  constituent  elements  of  these  tracts 
will  present  similar  destinations  and  possibilities  of  interruption,  i.e. 
of  reactions  involving  the  motor  mechanisms  at  the  different  levels 
in  the  brain  stem.  It  is  thus  much  more  difficult  in  the  brain  stem  than 
in  the  spinal  cord  to  describe  a  '  way  in  '  and  a  '  way  out.'  In  a 
chain  consisting,  say,  of  six  neurons,  a,  h,  c,  d,  e,  f  (Fig.  193),  though 
a  is  certainly  afferent  and  /  efferent,  it  must  always  be  more  or  less  a 
question  of  words  whether  we  regard  neurons  c  and  d  as  afferent  or 
efferent  in  character.  It  is  usual  in  our  classifications  to  be  guided 
chiefly  by  the  direction  of  such  impulses  in  relation  to  the  cerebral 
hemispheres.  All  tracts  going  up  to  the  cerebral  hemispheres  may  be 
involved  more  or  less  in  the  production  of  such  changes  in  the  nervous 
matter  of  these  hemispheres  as  are  associated  with  conscious  sensation. 
In  the  same  way  there  is  a  possibility  that  the  chains  of  neurons  which 
carry  impulses  in  a  descending  direction  may  be  involved  in  the  pro- 
duction of  voluntary  movement.  It  is  therefore  usual  to  classify  these 
t  wosets  of  tracts  as  ascending  and  descending,  or  as  afferent  and  efferent. 
If  we  adopt  such  a  classification  it  must  be  with  a  distinct  reservation 
that  tracts  which  apparently  are  going  downwards  may  play  a  greater 

28 


434  PHYSIOLOGY 

part  in  the  determination  of  sensation  than  in  the  deteimination  of 
movement,  and  that  there  may,  and  indeed  must,  be  a  reverberation  of 
impulses  through  these  ascending  and  descending  tracts,  so  that  it 
must  be  difficult  to  dissociate  the  various  elements  in  the  extremely 
complex  neural  events  which  are  involved,  say,  in  the  simplest  kind  of 
conscious  sensation. 

As  we  trace  out  the  evolution  of  the  brain  we  find  an  ever-increasing 
ubordination  of  the  lower  to  the  higher  centres,  so  that  in  man  himself 
many  reactions  which  in  the  lower  animals  are  carried  out  by  the  spinal 
cord  alone,  involve  the  educated  co-operation  of  the  cerebral  hemi- 
spheres. With  this  increased  control  there  is  a  corresponding  increase 
in  the  development  of  long  paths.  In  the  brain  of  a  fish,  for 
instance,  the  cerebral  hemispheres  are  connected  only  with  the  fore- 
brain  ;  a  little  higher  up  there  are  connections  between  the  hemi- 
spheres and  the  mid-brain  as  well.  The  chief  long  tracts  are  those 
which  run  between  the  thalamus,  the  mid-brain  or  the  hind-brain,  and 
the  spinal  cord.  With  the  huge  development  of  the  cerebral  hemi- 
spheres in  man  there  is  also  development  of  long  paths,  the  pyramidal 
tracts,  from  the  hemispheres  down  to  all  the  motor  mechanisms  of  the 
cord,  and  of  tracts  which  connect  all  parts  of  the  cortex  with  the  grey 
matter  of  the  pons  and  indirectly  with  the  cerebellum.  The  tracts 
which  in  the  lower  animals  were  of  supreme  importance  in  deter- 
mining subordination  of  lower  to  higher  centres,  of  immediate  reactions 
to  those  determined  by  the  organs  of  foresight,  dwindle  therefore 
in  importance.  Those  tracts,  such  as  the  thalamo-spinal,  tecto- 
spinal, vestibulo-spinal,  which  form  the  main  mass  of  the  white 
matter  of  the  brain  stem  in  lower  types  of  vertebrates,  become 
reduced  to  a  few  scattered  fibres  in  the  brain  of  man  and  are  insig- 
nificant as  compared  with  the  great  cerebro-bulbar  and  cerebro-spinal 
tracts. 

ASCENDING  TRACTS 

The  Tracts  of  the  Fillet.  The  fibres  which  enter  the  spinal 
cord  by  the  posterior  roots  pass  into  the  posterior  columns  and  along 
these  to  the  dorsal  column  nuclei,  the  nucleus  gracilis  and  the  nucleus 
cuneatus,  where  they  end  by  arborisations  among  the  cells  composing 
these  nuclei.  From  these  nuclei  the  axons  of  the  cells  pass  in  various 
directions,  the  chief  mass  of  them  forming  the  deep  arcuate  fibres. 
These  emerge  from  the  inner  side  of  the  nuclei  and  j)ass  through  the 
raphe  to  the  other  side  of  the  medulla,  where  they  turn  up  and  form 
the  definite  collection  of  longitudinal  fibres,  lying  dorsally  to  the 
pyramids,  which  is  known  as  the  main  tract  of  the  fillet,  or,  often, 
the  mesial  fillet.  As  these  fibres  traverse  the  pons  they  are  joined 
at  the  outer  side  by  a  number  of  bundles  which  are  derived  from  the 


THE  STRUCTURE  OF  THE  BRAIN  STEM 


43; 


Corpus  C5.1lo5um 


Rtd  Nucleus  .^ 

Subsf&.nfiA  Nigr£>.  ._ 
Peduncle   - 

Ctrebellum  --' 


/stnst  of  posifion 


Thalimo-Corri(il  FibrfS 


^  ^^^_  .C  lau  s  fr  u  m 


NLfnficukrNuclais 


Median  Fiiur 


Ptnf&rt  Nucleus 


Sf)ino-Cerebellar 
TrdLcfs 

(Co-ordina.tron  &^^ 
Muscular  Tont  / 


Pyr&m  id 

Detp  Arcu&re  Fibres 


Dorseil  Column  (direct) 


Crossed  Sensory  Fibres 
/pAin.  H£a.t&  Col(l\ 
llouch  &  Pressure  I 


Inferior  Olive 


Sp'O&l  Gdn^lion 
S|)in&l  Nerve  _ 


/^SCCMDIhG  hCRVe 
TRACTS. 


Fi(.:.  198.     Diagram  of  ascending  tracts  between  the  spinal  cord  and  brain  (Gordon 
Holmes),  with  the  probable  path  of  sensory  impulses. 


436  PHYSIOLOGY 

central  continuation  of  fibres  connected  with  those  derived  from  the 
cochlear  nerve.  This  part  is  known  as  the  lateral  fillet.  The  cells 
of  the  accessory  and  lateral  nuclei  of  the  cochlear  nerve  send  their 
axons  by  the  trapezium  to  the  superior  oHvary  nucleus  and  other 
small  masses  of  grey  matter  on  the  other  side.  In  these  nuclei  the 
fibres  for  the  most  part  terminate,  but  a  fresh  relay  of  neurons  carries 
on  the  impulses  and  forms  the  main  part  of  the  lateral  fillet.  These 
pass  up,  getting  more  dorsal  as  they  ascend,  and  finally  terminate 
in  the  inferior  corpora  quadrigemina.  The  mesial  fillet,  which  we 
can  regard  as  a  continuation  of  certain  spinal  tracts  upwards,  is  rein- 
forced throughout  the  whole  extent  of  the  medulla  and  pons  by 
fibres  originating  from  the  masses  of  grey  matter  in  which  the  sensory 
cranial  nerves  terminate.  Certain  of  these  fibres  may  form  a  distinct 
tract  in  the  formatio  reticularis,  known  as  the  central  or  thalamic 
tract  of  the  cranial  nerves.  Another  similar  tract  in  the  formatio 
reticularis  is  derived  from  the  central  terminations  of  the  fifth 
nerve,  and  is  known  as  the  trigemino-thalamic  tract.  All  these 
fibres  pass  up  in  the  tegmentum  of  the  mid-brain  and  finally  end, 
partly  in  the  grey  matter  of  the  subthalamic  region  and  partly  in 
the  grey  matter  of  the  thalamus  itself.  To  the  thalamus  are 
also  continued  a  few  fibres  from  the  lateral  fillet.  By  this  means 
the  head  ganglion  of  the  fore-brain  is  in  a  position  to  receive,  so  to 
speak,  samples  of  the  afferent  impressions  derived  from  every  sense- 
organ  of  the  body. 

The  Visual  Paths.  Two  classes  of  afferent  impressions  which 
arrive  at  the  optic  thalamus  are  probably  of  equal  importance  to  all 
the  other  afferent  impressions  taken  together.  These  are  impulses 
derived  from  the  organs  of  vision  and  of  smell.  The  greater  part  of 
the  fibres  composing  the  optic  nerves  arise  as  axons  of  the  ganglion- 
cells  of  the  retinae.  Passing  backwards,  the  nerves  of  the  two  sides 
join  in  the  optic  chiasma,  which  is  closely  attached  to  the  floor  of  the 
third  ventricle.  After  joining  in  the  chiasma  the  optic  nerves  are 
ajjparently  continued  round  the  crura  cerebri  as  the  optic  tracts. 
These  pass  round  on  each  side  and  can  be  seen  to  make  connection 
with  the  back  part  of  the  thalamus,  the  external  geniculate  body, 
and  the  superior  corpus  quadrigeminum.  Part  of  the  tract,  which  is^ 
sometimes  called  the  mesial  root,  passes  into  the  internal  geniculate 
body.  This  part  of  the  tract  has  probably  nothing  to  do  with  vision 
and  forms  a  commissure  running  in  the  optic  chiasma  connecting  the 
internal  geniculate  bodies  of  the  two  sides.  The  course  of  the  optic 
fibres  is  shown  in  the  diagram  (Fig.  199).  In  man  and  in  some  other 
mammals,  e.g.  dog,  monkey,  the  nerve  fibres  decussate  incom^iletely 
in  the  chiasma.  The  uncrossed  bundle  is  derived  from  the  outer  half 
of  the  retina  of  the  same  side,  whereas  the  crossed  bundle  is  derived 


THE  STRUCTURE  OF  THE  BRAIN  STEM  437 

from  the  mesial  half  of  the  retina  on  the  other  side.  The  right  optic 
nerve  thus  carries  all  the  impulses  originating  in  the  right  eye.  The 
right  optic  tract  carries  all  the  impulses  originating  from  stimuli 
occurring  in  the  left  field  of  vision.  It  will  be  remembered  that  vision 
in  man  is  binocular,  both  retinae  being  concerned  in  the  perception 
of  each  field  of  vision.  The  external  and  internal  geniculate  bodies 
may  be  regarded  as  extensions  of  the  optic  thalamus,  the  former 
in  special  relation  with  the 
organ  of  vision,  the  latter 
with  the  organ  of  hearing. 

The  olfactory  bulb  is  also 
connected  by  tracts  with  the 
thalamic  region,  probably 
through  the  column  of  the 
fornix  and  the  bundle  of  Vicq 
d'Azyr.  Since,  however,  the 
chief  connections  of  the  olfac- 
tory lobe  are  with  the  more 
primitive  portions  of  the  cere- 
bral hemispheres,  the  olfac- 
tory tracts  w^ill  be  more 
conveniently  treated  of  in 
connection  with  the  latter. 

The  Cerebellar  Paths. 
We  have  already  traced  out 
the  course  of  spinal  fibres 
which  terminate  in  the  cere- 
bellum. They  may  be  shortly 
summarised  as  follows  : 

(1)  The  posterior  or  direct 
cerebellar  tract,  originating  in 
Clarke's  column  of  cells  of 
same  side,  passing  up  in  the 
lateral   columns  and  by   the 

restiform  body  into  the  superior  vermis  of  the  middle  lobe  of  the 
cerebellum. 

(2)  The  anterior  cerebellar  tract  or  tract  of  Gowers,  originating  in 
the  grey  matter  of  both  sides  of  the  cord  and  passing  in  the  lateral 
columns  through  the  lateral  part  of  the  medulla  and  pons,  and 
finally  attaining  the  superior  vermis  through  the  superior  cerebellar 
peduncles. 

(3)  The  posterior  columns,  ending  chiefly  in  the  homolateral 
posterior  column  nuclei.  From  these  nuclei,  though  the  great  mass  of 
fibres  passes  into  the  fillet,  a  certain  number  from  the  nuclei  of  both 


v 


i 

PULVINAf 

1 " 

% 

CORP.GEh 

CORP.GEN. 

INT. 

quad(A,.v4 

Fig.  199.  Diagram- 
matic representa- 
tion of  the  optic 
tracts  and  their 
connections. 

(Cunningham.) 


438  PHYSIOLOGY 

sides  join  the  restiform  body  to  pass  into  the  middle  lobe  of  the 
cerebellum. 

In  the  medulla  these  afferent  tracts  of  the  cerebellum  are  joined 
by  the  following  sets  of  fibres  : 

1.  The  olivo-cerebellar. 

2.  The  vestibulo- cerebellar. 

3.  A  few  fibres  from  the  chief  sensory  nuclei,  including  those  of  the 
vago- glossopharyngeal  nerves. 

All  these  fibres  terminate  in  the  cortex,  chiefly  of  the  middle  lobe. 
From  the  cortex  of  this  lobe  fibres  pass  to  the  central  and  roof  nuclei 
of  the  cerebellum,  namely,  the  nucleus  dentatus,  the  nucleus  emboli- 
formis,  the  nucleus  fastigii,  and  the  nucleus  giobosus.  The  efferent 
tracts  of  the  cerebellum  start  from  these  central  nuclei,  no  fibres 
which  originate  in  the  cortex  of  the  cerebellum  apparently  leaving 
the  precincts  of  this  organ.  Some  of  these  efferent  fibres  of  the 
cerebellum  will  be  better  described  with  the  descending  tracts  of  the 
brain  stem.  Of  those  which  take  an  ascending  direction,  the  great 
bulk  are  contained  in  the  superior  cerebellar  peduncles.  These 
originate  for  the  most  part  in  the  dentate  nucleus  and  the  nuclei 
emboliformis  and  giobosus.  As  the  superior  peduncles  run  forwards 
•they  sink  below  the  posterior  corpora  quadrigemina,  and  in  the  teg 
mentum,  below  the  Sylvian  iter,  decussate  with  the  tract  of  the 
opposite  side  to  pass  to  the  red  nucleus.  In  the  red  nucleus  many  of 
the  fibres  end,  some,  however,passing  through  the  nucleus  together  with 
fibres  derived  from  the  cells  of  the  red  nucleus  itseK  to  end  in  the 
thalamus  and  in  the  grey  matter  of  the  subthalamic  region. 

DESCENDING   TRACTS 
The  chief  descending  tracts  having  their  origin  in  the  brain  stem 
are  the  rubro-spinal  bundle   or   bundle   of    Monakow,  the  complex 
system  of  fibres  known  as  the  posterior  longitudinal  bundle,  and  the 
vestibulo-spinal  fibres  from  the  upper  part  of  the  medulla. 

(1)  The  RUBRO-SPINAL  FIBRES  Originate  in  the  red  nucleus.  They 
cross  the  median  line  and  run  down,  at  first  in  the  tegmentum  and 
later  in  the  lateral  column  of  the  medulla  oblongata  and  cord.  In 
their  passage  they  communicate  with  the  various  motor  nuclei  of  the 
cranial  nerves.  They  can  be  traced  to  all  segments  of  the  cord,  where 
they  terminate  in  connection  with  the  anterior  horn-cells. 

(2)  The  POSTERIOR  longitudinal  bundle.  This  bundle  is  to 
be  seen  in  all  sections  through  the  brain  stem  below  the  level  of  the 
oculo-motor  nucleus.  It  consists  of  fibres,  some  of  which  pass  upwards, 
while  others  pass  downwards.  Most  of  the  fibres  take  origin  in  the 
cells  of  Deiters'  nucleus  and  of  the  reticular  formation  of  the  pons, 
medulla,  and  mid-brain,  as  well  as  from  certain  cells  in  the  sensory 


THE  STRUCTURE  OF  THE  BRA IX  STEM 


439 


Opfic 
Thil&muS 


Ca^psulej- 


LenticulArl 
Nuckus  J 

Subsi'AnfiA  Nidra.  _  _ 
Rubro-Spinil  Tract 


Deittrs  Nucleus 


-Cldusrru.n 


_  _-  Rtd  Nucleus 
Pyramidal  TrAct 

-   -  Dinfd^k  Nucleus 


trior  Ulive 


Vcstibulo  Spinal  Tr^c^ 


Crossed  Pyramidal  Tract 


Direct  Pyrdmidal  Tract 

D65C6MDmG  M6RV/E 
TRACTS. 


Fig.  200.  Schema  of  course  taken  by  chief  descending  tracts  of  biaiu  stem.  (Gordon 
Holmes.)  The  tract  in  red,  to  the  right  of  the  rubro-spinal  tract,  includes  tlie 
posterior  longitudinal  bundle,  together  with  the  fibres  of  the  thalaino-spinal  and 
tecto-spuial  tracts. 


440  PHYSIOLOGY 

nucleus  of  the  fifth  nerve.  The  fibres  traced  upwards  can  be  seen  to 
send  collaterals  to  end  in  the  various  parts  of  the  nuclei  of  the  third, 
fourth,  and  sixth  nerves.  Lower  down  it  becomes  continuous  with 
the  anterior  basis  bundle  of  the  spinal  cord  and  merges  in  the  inter- 
nuncial  fibres  which  serve  to  connect  the  various  levels  of  the  cord. 
Some  of  the  fibres,  which  are  descending,  are  derived  from  a  small 
nucleus,  the  so-called  nucleus  of  the  posterior  longitudinarl  bundle, 
which  is  found  in  the  grey  matter  at  the  side  of  the  posterior  part  of 
the  third  ventricle.  This  bundle  also  receives  fibres  from  the  superior 
olivary  body.  It  is  one  of  the  earliest  to  undergo  myelination  in  the 
foetus  {cp.  also  Fig.  205,  p.  461). 

(3)  The  VESTiBULO-SPiNAL  TRACT  takes  origin  for  the  most  part  in 
the  cells  of  Deiters'  nucleus.  The  fibres  pass  down  in  the  anterior 
part  of  the  spinal  cord  and  terminate  in  the  anterior  horns.  They 
are  sometimes  known  as  the  antero-lateral  descending  tract.  It  is 
probably  through  this  tract  that  the  cerebellum  is  able  to  indirectly 
affect  the  activity  of  the  motor  mechanisms  of  the  cord. 

Two  other  descending  tracts  which  are  important  m  the  lower 
vertebrates  are  insignificant  in  man.  These  are  the  thalamo-spinal 
tract,  consisting  of  descending  fibres  derived  from  the  optic  thalamus, 
and  the  tecto-spinal  tract,  containing  fibres  derived  from  the  roof  of 
the  mid-brain.  In  the  mid-  and  hind-brain  these  fibres  run  in  the 
tegmentum.  In  the  cord  they  are  found  in  the  anterior  columns. 
The  olivo-spinal  tract,  which  is  supposed  to  originate  in  the  olivary 
body,  forms  a  small  tract  in  the  cervical  region  near  the  surface, 
opposite  the  lateral  angle  of  the  anterior  horn. 


SECTION  XII 

THE  FUNCTIONS  OF  THE  BRAIN  STEM 

The  brain  stem  may  be  taken  to  include  all  those  parts  lying 
between  the  cerebral  hemispheres  and  the  spinal  cord,  from  the 
optic  thalamus  in  front  to  the  medulla  oblongata  behind.  The 
brain  may  be  divided  into  the  following  parts  from  before  back  : 

(1)  Thalamencephalon,  including  the  corpus  striatum,  the  cerebral 
hemispheres  and  rhinencephalon,  or  olfactory  lobes. 

(2)  Diencephalon,  i.e.  the  fore-brain,  especially  the  optic  thalamus. 

(3)  Mesencephalon,  or  mid-brain,  including  the  quadrigemina,  the 
iter  of  Sylvius,  and  the  crura  cerebri. 

(4)  Metencephalon,  composed  of  the  pons  Varolii,  the  upper  part 
of  the  fourth  ventricle,  and  the  cerebellimi. 

(5)  Myelencephalon,  or  bulb,  consisting  of  the  medulla  oblongata. 
We  may  get  some  idea  of  the  part  played  by  these  different  regions 

of  the  brain  in  determining  the  reactions  of  the  individual  as  a  whole 
by  examining  the  behaviour  of  the  animals  in  whom  all  the  rest  of  the 
brain  in  front  of  the  part  in  c[uestion  has  been  removed.  If,  however, 
we  take  into  account  the  numberless  connections  existing  between  the 
different  levels  in  the  central  nervous  system,  the  interdependence 
between  the  different  portions,  and  the  subordination,  especially  in 
the  higher  animals,  of  the  functions  of  the  lower  to  those  of  the  higher 
levels,  we  must  acknowledge  that  such  experiments  can  only  give  us 
an  imperfect  idea  of  the  possibilities  of  each  level  when  in  connection 
with  all  other  portions  of  the  nervous  system. 

THE  FUNCTIONS  OF  THE  MEDULLA  OBLONGATA 
OR  MYELENCEPHALON 

The  possibilities  of  any  given  nervous  centre  are  determined  by 
the  afferent  impressions  which  enter  it,  and  by  the  connections  made 
by  the  nerves  carrying  these  impulses  with  the  motor  tracts  within 
the  centre.  The  bulb  receives  afferent  impressions  of  '  taste  '  from 
the  tongue  through  the  nervus  intermedins,  from  the  alimentary 
canal  as  low  as  the  ileocolic  sphincter,  from  the  lungs,  the  heart, 
and  the  larger  blood-vessels,  i.e.  from  the  most  important  of  the 
viscera  of  the  body,  by  the  fibres  of  the  vago- glossopharyngeal  nerves. 
Its  only  skeleto-motor  centre  is  that  for  the  muscles   of  the  tongue 

441 


442  PHYSIOLOGY 

(the  hypoglossal).  It  sends  also  efferent  fibres  to  the  viscera,  which 
arise  from  cells  in  the  nucleus  ambiguus.  These  fibres  carry  motor 
impulses  to  the  muscles  of  the  larynx  and  bronchi,  and  to  the 
oesophagus,  stomach,  and  intestines,  secretory  fibres  to  the  stomach 
and  inhibitory  fibres  to  the  heart. 

At  the  upper  border  of  the  bulb  enter  also  the  fibres  of  the  eighth 
nerve,  carrying  important  impressions  from  the  organ  of  hearing  and 
the  organ  of  static  sense.  These  will  be  in  all  probability  divided  or 
injured  in  isolating  the  bulb  from  the  higher  portions  of  the  brain. 
While  in  connection  with  the  upper  portions  of  the  brain,  the  bulb 
receives  also  afferent  impressions  from  the  skin  of  the  face,  and  the 
mucous  membrane  of  the  nose  and  mouth  through  the  descending 
branches  of  the  root  of  the  fifth  nerve,  which  pass  down  superficially 
to  the  tubercle  of  Rolando.  When  in  connection  with  the  cord  the 
medulla  receives  afferent  imj)ressions  from  the  whole  surface  of  the 
body  and  from  all  the  muscles  and  joints  through  the  posterior  column 
nuclei. 

The  bulbo-spinal  animal,  i.e.  one  in  whom  a  section  has  been 
carried  out  at  the  upper  boundary  of  the  medulla,  differs  from  the 
spinal  animal  chiefly  in  the  maintenance  of  the  nexus  between  the 
visceral  functions  and  the  skeleto-motor  functions  of  the  body.  After 
removal  of  all  the  brain  in  front  of  the  bulb,  the  animal  still  continues 
to  breathe  regularly  and  automatically.  The  blood  pressure  and 
the  pulse  rate  remain  normal,  and  all  three  mechanisms,  respiration, 
pulse  rate,  blood  pressure,  may  be  affected  reflexly  by  appropriate 
stimuli,  or  may  be  altered  in  consequence  of  central  stimulation  of  the 
medulla. 

In  addition  to  the  reflex  mechanisms  of  locomotion,  which  are 
evident  in  the  spinal  animal,  the  bulbo-spinal  animal  shows  a  greater 
degree  of  solidarity  in  its  responses.  It  is  easier  to  evoke  movement 
of  all  four  limbs.  In  the  frog,  if  the  eighth  nerve  has  been  left  intact, 
there  is  a  certain  power  of  equilibration  left,  and  the  animal  when 
laid  on  its  back  tries  to  right  itself  and  usually  succeeds. 

It  is  in  this  portion  of  the  central  nervous  system  that  have  been 
located  the  gxeat  majority  of  the  so-called  centres.  By  a  statement, 
that  the  centre  of  such-and-such  movement  or  function  is  situated 
in  the  medulla,  we  mean  merely  that  the  integrity  of  the  medulla,  or 
certain  parts  of  it,  is  essential  for  the  carrying  out  of  the  function. 
Every  function,  for  instance,  in  which  impulses  passing  up  the  vagus 
nerves  are  involved,  is  necessarily  dependent  on  the  integrity  of  these 
nerves  and  their  central  connections,  and,  since  these  are  situated 
in  the  medulla,  the  centres  for  these  functions  are  also  located  in  this 
region.  From  a  broad  standpoint  the  medulla  or  bulb  may  be  looked 
upon  as  a  ganglion,  or  a  collection  of  ganglia,  whose  main  office  is  to 


THE  FUNXTION'S  OF  THE  BRAIX  STEM  443 

guard  and  preside  over  the  working  of  the  mechanisms  at  the  anterior 
opening  of  the  body  ;  by  means  of  which  food  is  seized,  tasted,  taken 
into  the  alimentary  canal,  and  finally  digested.  The  respiratory 
apparatus  belongs  to  the  same  system  and  is  innervated  through 
the  same  nerve  channels.  Hence  the  various  events  in  alimentation, 
such  as  deglutition,  vomiting,  mastication,  or  in  the  allied  respiratory 
functions,  such  as  phonation,  coughing,  and  respiration  itself,  are 
endowed  with  centres  in  this  part  of  the  brain.  In  connection  with 
the  termination  of  the  vagus  nerves  of  this  part  of  the  brain  is  the 
location  here  of  the  chief  vaso-motor  centre,  i.e.  in  a  region  which 
is  in  close  proximity  to  the  endings  of  the  chief  afferent  nerves  from 
the  heart  and  larger  blood-vessels  and  to  the  nucleus  of  the  efferent 
controlling  nerve  to  the  heart. 

THE  METENCEPHALON  (PONS  VAROLII  AND  CEREBELLUM) 
Destruction  of  the  brain  at  the  front  of  the  fourth  ventricle  and 
just  behind  the  posterior  quadrigemina  will  leave  the  animal  with  a 
central  nervous  system,  which  is  in  connection  by  efferent  nerves  with 
the  whole  musculature  of  the  body  (with  the  exception  of  certain 
eye  muscles)  and  which  receives  impressions  through  the  spinal  cord 
from  the  whole  surface  of  the  trunk  and  limbs,  and  through  the 
fifth  nerve  from  the  face  and  head,  and  also  the  higher  specialised 
impressions  from  the  organ  of  hearing  and  the  organ  of  static  sense. 
The  impressions  from  the  two  great  projicient  senses  of  smell  and 
sight  would  be  wanting. 

Such  an  animal  presents  considerable  advance  in  the  complexity 
of  its  reactions  above  one  possessing  only  spinal  cord  and  bulb.  The 
frog,  for  instance,  after  such  an  operation,  can  still  walk,  spring,  and 
swim  ;  when  placed  on  a  turntable  it  reacts  to  passive  rotation  by 
turning  its  head  in  the  opposite  direction.  On  stroking  its  back  it 
croaks.  If  the  cerebellum  be  also  removed  the  animal  becomes 
spontaneously  active  and  crawls  about  until  it  is  blocked  by  some 
obstacle.  In  this  condition  there  is  great  activity  of  the  swallowing 
reflex.  Anything  which  touches  the  miuth  is  snapped  at.  If 
placed  on  its  back  the  frog  at  once  rights  itself. 

In  the  mammal  a  similar  increase  of  reflex  activity  is  observed 
though  the  power  of  progression  is  not  retained. 

THE  MESENCEPHALON  OR  MID-BRAIN 
A  section  in  front  of  the  anterior  corpora  quadrigemina  would 
leave  the  animal  with  the  nervous  system  receiving  all  normal  sensory 
impressions,  with  the  exception  of  the  olfactory,  and  with  efferent 
paths  to  all  the  muscles  of  the  body,  including  those  of  the  eye.  In 
the  mammal  such  an  operation  brings  about  a  condition  known  as 


444  PHYSIOLOGY 

'  decerebrate  rigidity.'  Though  respiratory  movements  continue 
normally,  the  whole  musculature  is  in  a  cataleptic  condition,  the 
elbows  and  knees  being  extended  and  resisting  passive  flexion  ;  the 
tail  is  stiff  and  straight,  the  neck  and  head  retracted.  This  condition 
seems  to  depend  on  an  over-activity  of  the  reflex  tonic  functions  of  the 
lower  centres.  That  it  is  reflex  is  shown  by  the  fact  that  the  rigidity 
is  at  once  abohshed  in  a  limb  on  dividing  the  appropriate  posterior 
roots.  The  position  of  the  limbs  may  be  also  modified  by  sensory 
stimuli.  A  similar  condition  of  increased  tonus  is  observed  in  the  frog. 
The  apparatus  for  emotional  expression  is  still  intact  though  some- 
what modified,  and  an  impression  which  would  give  rise  to  pain  in  the 
intact  animal  may  cause  vocalisation  in  an  animal  in  whom  the  brain 
above  the  mesencephalon  has  been  destroyed. 

THE  BRAIN  STEM  AS  A  WHOLE  (INCLUDING  THE  THALAM- 
ENCEPHALON,  OR  OPTIC  THALAMI) 
The  introduction  of  the  head  ganglia  of  the  brain  stem,  viz.  the 
optic  thalami,  completes  in  the  lower  animals  at  all  events  the  appa- 
ratus for  immediate  response  to  stimulus.  The  powers  of  such  an 
apparatus  may  be  studied  by  examining  the  behaviour  of  an  animal 
in  whom  the  cerebral  hemispheres  have  been  destroyed.  The  result 
Trf^is  operation  varies  according  to  the  type  of  animal  chosen,  though 
all  types  present  certain  common  features.  When  a  frog's  cerebral 
hemispheres  have  been  excised,  a  casual  observer  would  not  at  first 
notice  anything  abnormal  about  the  animal.  It  sits  up  in  its  usual 
position,  and  on  stimulation  may  be  made  to  jump  away,  guiding 
itself  by  sight,  so  that  it  avoids  any  obstacles  in  its  path.  Movements 
of  swallowing  and  breathing  are  normally  carried  out.  The  animal, 
thrown  on  to  its  back,  immediately  turns  over  again.  If  put  into 
water,  it  swims  about  until  it  comes  to  a  floating  piece  of  wood  or 
any  support,  when  it  crawls  out  of  the  water  and  sits  still.  If  it  be 
placed  on  a  board  and  the  board  be  inclined,  it  begins  to  crawl  slowly 
up  it,  and  by  gradually  increasing  the  inclination  may  be  made  to 
crawl  up  one  side  and  down  the  other.  But  a  striking  difference 
between  it  and  a  normal  frog  is  the  almost  entire  absence  of  sponta- 
neous motion — that  is  to  say,  motion  not  reflexly  provoked  by  changes 
immediately  taking  place  in  its  environment.  All  psychical  phenomena 
seem  to  be  absent.  It  feels  no  hunger  and  shows  no  fear,  and  will 
suffer  a  fly  to  crawl  over  its  nose  without  snapping  at  it.  "  In  a  word, 
it  is  an  extremely  complex  machine,  whose  actions,  so  far  as  they  go, 
tend  to  self-preservation  ;  but  still  a  machine  in  this  sense,  that  it 
seems  to  contain  no  incalculable  element.  By  applying  the  right 
sensory  stimulus  to  it  we  are  almost  as  certain  of  getting  a  fixed 
response  as  an  organist  is  when  he  pulls  out  a  certain  stop." 


THE  FUNCTIONS  OF  THE  BRAIN  STEM  Ur> 

According  to  Schrader  and  Steiner,  if  care  be  taken  not  to  injure 
the  optic  thalami,  spontaneous  movements  may  be  occasionally 
observed  after  removal  of  the  cerebral  hemispheres.  On  the  approach 
of  winter  such  a  frog  has  been  observed  to  bury  itself  in  order  to  hiber- 
nate, and  with  spring  to  resume  activity  and  to  feed  itself  by  catching 
insects.  The  behaviour  of  such  decerebrate  animals  depends  on  the 
part  taken  in  the  initiation  of  movement  and  adapted  reactions  by 
stimuli  entering  through  the  higher  sense-organs.  Thus  an  ordinary 
bony  fish  after  ablation  of  the  cerebral  hemispheres  maintains  its  normal 
equilibrium  in  water.  It  is  continually  swimming  about,  stopping  only 
when  it  reaches  the  side  of  the  vessel  or  when  worn  out  by  fatigue. 
Here,  again,  if  the  thalami  and  optic  lobes  be  intact  the  fish  has  been 
observed  to  show  very  little  difference  from  a  normal  animal  and  to 
possess  the  power  of  distinguishing  edible  from  non-edible  material. 
On  the  other  hand,  in  the  elasmobranch  fishes,  which  depend  mainly 
upon  their  olfactory  apparatus  as  a  guide  to  movement,  the  removal 
of  the  cerebral  hemispheres  with  the  olfactory  lobes,  or  of  the  latter 
alone,  produces  complete  immobility  and  absence  of  spontaneous 
movement,  even  though  the  optic  thalami  and  optic  lobes  may  be 
intact. 

In  the  bird  the  cerebral  hemispheres  may  be  removed  with  ease. 
A  decerebrate  pigeon,  if  its  optic  lobes  be  intact,  walks  about  avoiding 
all  obstacles,  and  may  even  fly  a  short  distance.  In  the  dark,  i.e.  in 
the  absence  of  visual  impressions,  it  remains  perfectly  still.  The  bird, 
however,  is  unable  to  recognise  food,  or  enemies,  or  individuals  of  the 
opposite  sex  ;  it  shows  no  fear  and  responds  to  stimuli  like  the  brainless 
frog  described  above. 

Goltz  has  succeeded  in  the  dog  in  removing  the  whole  of  the  cerebral 
hemispheres  in  three  operations.  The  dog  was  kept  alive  for  eighteen 
months  after  the  final  operation.  It  was  able  to  walk  in  normal 
fashion  and  spent  the  greater  part  of  the  day  in  walking  up  and 
down  its  cage.  At  night  it  would  sleep  and  then  required  a  loud 
sound  to  awaken  it.  It  reacted  to  stimuli  in  a  normal  fashion,  shutting 
its  eyes  when  exposed  to  a  strong  light,  shaking  its  ears  in  response  to  a 
loud  sound.  On  pinching  its  skin  it  attempted  to  get  away,  snarling  or 
turning  round  and  biting  clumsily  at  the  experimenter's  hand.  It 
had  no  power  to  recognise  food  and  had  to  be  fed  by  placing  food  in  its 
mouth,  though,  if  this  food  were  mixed  with  a  bitter  substance,  such 
as  quinine,  it  was  at  once  rejected.  The  dog  never  showed  any  signs 
of  pleasure,  or  recognition  of  the  persons  that  fed  it,  or  of  fear. 
Removal  of  the  hemispheres  had  thus  produced  loss  of  all  understand- 
ing and  memory.  There  was  no  sign  of  conscious  intelligence,  and 
all  the  actions  of  the  animal  must  be  regarded  as  reflex  responses  to 
immediate  excitation. 


U6  PHYSIOLOGY 

With  the  development  of  the  cerebral  hemispheres  in  the  higher 
mammals  there  is  a  considerable  shifting  of  motor  reactions  from 
those  which  are  immediate  and  '  fatal '  or  inevitable  to  those  which 
are  educatable.  The  cerebral  hemispheres  in  man  take  a  large  part 
in  the  determining  of  even  the  common  reactions  of  everyday  life. 
Ablation  of  the  hemispheres  therefore,  or  even  part  of  the  hemispheres, 
in  the  ape  and  man  gives  rise  to  much  more  lasting  symptoms  than  is 
the  case  in  the  animals  we  have  just  studied.  These  defects  we  shall 
have  to  consider  more  fully  later.  The  results,  however,  obtained  on  the 
lower  animals,  from  the  dog  downwards,  show  that  the  brain  stem,  from 
the  head  ganglion  of  the  optic  thalamus  back  to  the  medulla,  with  the 
spinal  cord,  represents  a  complex  mechanism  which  can  be  played 
upon  by  impulses  received  through  all  the  sensory  apparatus  of  the 
body,  and  is  able  to  adjust  the  motor  and  visceral  reactions  to  the 
immediate  environment  of  the  animal. 

Certain  of  these  immediate  reactions  are  susceptible  of  further 
physiological  analysis.  We  have  seen  that  the  spinal  cord  contains 
the  co-ordinated  mechanism  for  the  movement  of  the  limbs.  We  may 
now  discuss  how  the  movements  of  the  limbs  are  co-ordinated  with 
those  of  the  trunk  and  head  in  the  maintenance  of  the  unstable  position 
of  the  animal  in  standing  and  in  locomotion.  For  this  purpose  there 
has  been  developed  the  great  mass  of  nerve  matter  in  the  roof  of  the 
metencephalon,  viz.  the  cerebellum. 


SECTION  XIII 

THE  FUNCTIONS  OF  THE  CEREBELLUM 

In  discussing  the  spinal  mechanisms  for  the  carrying  out  of  co- 
ordinated movements  we  have  seen  that  in  every  case  the  reflex 
discharge  is  associated  and  regulated  by  ajSerent  impressions.  These 
afferent  impressions  can  be  divided  into  two  main  groups. 

In  the  first  group  may  be  placed  those  due  to  the  changes  in 
the  environment  of  the  animal,  working  on  sensory  structures  or 
'  receptors,'  of  varying  qualitative  sensibility,  in  the  surface  of  the 
body.  Among  these  receptors  are  those  which  are  excited  by  the 
mechanical  stimuli  of  pressure,  those  excited  by  changes  of  tempera- 
ture, and  those  excited  by  nocuous  or  harmful  impressions,  such  as 
would,  in  the  presence  of  consciousness,  give  rise  to  pain.  At  the  fore 
end  of  the  body  we  have  in  addition  the  special  receptor  organs 
excited  by  waves  of  light  or  of  sound.  The  action  of  any  of,  these 
impressions  falling  with  sufficient  intensity  on  any  part  of  the  body  is 
to  evoke  an  appropriate  reflex  movement,  such  as  the  flexor  reflex  in 
response  to  nocuous  stimulus  applied  to  the  foot,  or  the  stepping,  or 
extensor,  reflex  excited  by  steady  pressure  on  the  sole  of  the  foot. 

The  integrity  of  the  nerve  paths  carrying  these  afferent  impres- 
sions and  of  the  motor  paths  to  the  muscles  is  not,  however,  sufficient. 
A  secondary  set  of  afferent  impulses  is  essential  in  order  to  guide 
and  regulate  the  extent  of  the  resultant  discharge.  These  secondary 
afferent  impulses  start  in  the  deep  tissues,  viz.  the  muscles,  joints, 
and  ligaments,  which  are  provided  with  special  sense-organs  capable 
of  being  stimulated  by  the  mechanical  changes  of  tension  or  pressure 
set  up  by  the  movements  themselves.  The  importance  of  these 
impressions  for  the  carrying  out  of  muscular  movements  is  shown 
by  the  ataxia  which  is  the  result  of  injury  to  the  corresponding 
afferent  nerves.  Degeneration  of  the  nerves  to  muscles,  or  section 
of  the  afferent  roots,  causes  marked  ataxia  of  the  movements  of  the 
limb,  whereas  no  such  result  follows  section  of  all  the  cutaneous 
nerves  supplying  the  surface  of  the  limb  with  sensibility.  To  this 
system  of  afferent  nerves  Sherrington  has  given  the  name  of  the  '  pro- 
prioceptive '  system,  since  it  is  excited,  not  directly  by  changes  in 
the  environment,  but  by  alteration  in  the  animal  itself.  It  is  respon- 
sible for  reactions  differing  in  many  respects  from  those  which  are  the 

447 


448  PHYSIOLOGY 

immediate  result  of  stimulation  of  the  other  system,  the  '  exterocep- 
tive,' which  is  distributed  over  the  surface  of  the  body.  Since  it  is 
excited  by  the  movement  of  the  muscles  themselves,  i.e.  by  the  first 
result  of  the  reaction  to  external  stimulus,  it  serves  as  a  governing 
mechanism  to  regulate  the  extent  of  each  motor  discharge.  Its 
excitation  not  only  prevents  over-action  of  the  muscles,  but  may 
evoke  a  compensatory  reflex  in  an  opposite  direction  to  the  reflex 
immediately  excited  from  the. skin.  A  marked  feature  of  this  system 
is  its  tendency  to  continued  or  tonic  activity.  The  steady  slight 
contraction  which  is  observable  in  most  skeletal  muscles,  and  is 
spoken  of  as  their  '  tone,'  is  quite  independent  of  the  surface  sensi- 
bility and  depends  entirely  on  the  proprioceptive  system  of  the 
muscles  and  their  accessory  structures. 

In  the  decerebrate  animal  the  rigidity  of  a  limb  disappears  at 
once  after  section  of  its  afferent  roots,  though  it  is  unaltered  by 
division  of  the  main  skin  nerves.  This  tonus  does  not  affect  all 
muscles  to  an  equal  degree.  In  every  limb  there  is  a  predominance  of 
tonus  in  certain  muscles  above  others,  so  that  the  result  on  the  whole 
limb  is  an  attitude  or  posture  which  is  typical  of  the  limb  or  the 
animal.  Thus  the  spinal  frog  takes  up  an  attitude  which  is  very 
different  from  that  which  would  be  impressed  on  it  by  gravity  in  the 
absence  of  muscular  activity.  If  one  of  its  hind  limbs  be  extended 
gently,  it  soon  draws  it  up  to  reproduce  the  same  crouching  position. 
The  posture  of  the  limb  is  therefore  a  result  of  afferent  impressions 
continually  ascending  its  proprioceptive  nerves  and  exciting  a  tonic 
activity  which  predominates  in  certain  definite  muscles.  This  posture, 
as  carried  out  by  the  spinal  cord,  is  a  segmental  response.  It  deter- 
mines the  relation  of  the  limb  to  the  trunk,  and  to  a  less  extent  of 
the  fore  limbs  to  one  another.  It  is  not  concerned  with  the  relation 
of  the  animal  as  a  whole  to  its  environment,  and  only  to  a  slight 
extent  with  the  maintenance  of  equilibrium  in  the  presence  of  the 
continually  acting  force  of  gravity.- 

In  the  evolution  of  the  nervous  system  there  has  been  a  continual 
subordination  of  the  hinder  parts  to  the  head  end,  in  consequence 
of  the  development  at  this  end  of  the  all-important  distance  receptors, 
the  impulses  from  which  take  a  predominating  part  in  determining 
the  reactions  of  the  body  as  a  whole.  In  fact  the  subordination 
of  one  part  of  the  central  nervous  system  to  another  is  in  direct 
relation  to  the  importance  of  the  afferent  impulses  arriving  at  each 
portion  of  the  system.  Thus  the  vaso-motor  centres  segmentally 
distributed  throughout  the  spinal  cord  are  subject  to  the  vaso-motor 
centre  in  the  medulla,  which  is  developed  at  the  point  of  entry  of 
the  vagus  nerves,  i.e.  the  chief  afferent  nerves  from  the  heart  and 
large  blood-vessels.     The  collections  of  grey  matter  presiding  over  the 


THE  FUNCTIONS  OF  THE  CEREBELLUM 


449 


segmental  reactions  of  the  intercostal  nauscles  are  entiiely  subordinated 
to  the  grey  matter  in  the  medulla  around  the  entry  of  the  vagus  fibres 
from  the  lungs. 

This  subordination  of  the  hinder  to  the  anterior  sense-organs  is 
paralleled  in  the  case  of  the  proprioceptive  system.  Entering  the 
hind- brain  at  the  upper  border  of  the  medulla  is  the  eighth  nerve, 
composed  of  two  parts  which  differ  widely  in  functions,  viz.  the 
cochlear  division  and  the  vestibular  division.  The  former  is  entiiely 
concerned  with  the  reception  of  sound  waves,  and  is  therefore  the 
auditory  nerve.  The  vestibular  nerve,  which  is  distributed  to  the 
rest  of  the  membranous  labyrinth,  must  be  assigned  to  the  proprio- 
ceptive system.  The  labyrinth  is  practically  a  double  organ.  The 
primitive  auditory  sac  arises  as  a  simple  involution  of  the  surface. 
In  the  com-se  of   development  the  front  part  is  modified  to  form 


Fig.  201.  Diagram  of  au  otolith  organ,  to  show^how  alteratioiis 
in  its  position  will  cause  the  weight  of  the^  otolith  (ot.)  to 
press  on  difEerent  sense-cells,  and  therefore  to  affect  different 
nerve  fibres. 

the  canal  of  the  cochlea,  which  is  set  apart  entirely  for  the  reception 
of  sound.  From  the  back  part  there  are  formed  two  sacs — the 
saccule  and  utricle — and  the  three  semicircular  canals.  The 
saccule  and  the  utricle,  which  receive  each  a  large  branch  of  the 
vestibular  nerve,  may  be  regarded  as  representing  the  otolith  organ, 
which  is  found  in  almost  all  classes  of  animals.  The  craj^sh,  for 
instance,  at  the  base  of  its  antenna)  presents  a  small  sac  which  is 
lined  with  hairs  and  richly  supplied  with  nerves.  In  this  sac  a  small 
calcareous  particle  rests  on  the  hairs.  It  is  evident  that  the  incidence 
of  the  pressure  of  the  small  stone  or  otolith  on  the  hairs  will  vary 
according  to  the  position  of  the  animal  (Fig.  201),  so  that  any  change 
in  the  position  of  the  head  will  be  at  once  attended  by  alteration  in 
the  nerve  fibres  which  have  been  stimulated  by  the  pressure  of  the 
otolith,  and  therefore  in  the  nature  of  the  impulses  flowing  to 
the  central  nervous  system.  The  iniportanre  of  those  impulses  in 
regulating  the  locomotion  and  the   maintenaiicc  uf  Uie  equilibrium 

•-"J 


45U  PHYSIOLOGY 

of  the  animal  is  well  shown  if  the  otolith  be  replaced  by  a  small 
fragment  of  iron.  Under  normal  circumstances  the  iron  particle  will 
act  quite  as  well  as  an  otohth.  If,  however,  a  powerful  magnet  be 
brought  in  the  neighbourhood  of  the  animal,  the  pressure  of  the 
particle  will  not  be  determined  simply  by  gravity  and  therefore  by 
the  position  of  the  animal,  so  that  there  will  be  a  dissonance  between 
the  impulses  arriving  from  the  otolith  organ  and  those  arising  from 
the  sense-organs  of  the  body,  and  marked  disorders  of  equiUbrium 
are  the  result. 

In  the  saccule  and  utricle  the, vestibular  nerve  ends  in  similar 
otohth  organs  known  as  the  maculae  acousticse.  Each  of  these  is  a 
small  elevation  covered  with  long  hairs  and  supplied  with  nerves. 
One  or  two  calcareous  secretions  or  otohths  are  embedded  in  the 
hairs,  so  that  any  change  in  position  will  cause  a  corresponding  change 
in  the  nerve  fibres  which  are  being  excited  by  the  weight  of  the 
otoliths.  The  semicircular  canals,  which  lie  in  the  three  planes  of 
space,  are  also  provided  with  end-organs,  somewhat  similar  in  struc- 
ture to  the  maculae  acousticse,  but  devoid  of  otoliths.  They  are 
excited  by  mass  movements  of  the  fluid  endolymph,  hlhng  the 
canals,  which  are  set  up  by  rotation  of  the  head. 

Since  the  nervous  apparatus  of  the  labyrinth  is  excited  not  by 
changes  in  the  environment,  from  which  it  is  carefully  shielded,  but 
by  changes  in  the  animal  itself,  we  are  justified  in  assigning  it  to 
the  proprioceptive  system,  of  which  indeed  it  represents  the  most 
important  receptor.  Just  as  the  proprioceptive  nerves  of  a  limb 
are  responsible  for  the  tonus  of  the  limb  muscles,  so,  as  Ewald  has 
shown,  each  labyrinth  is  responsible  to  a  considerable  degree  for 
the  tonus  of  the  corresponding  side  of  the  body.  Extirpation  of 
one  labyrinth  causes  a  lasting  loss  of  tone  in  the  muscles  of  the  same 
side.  A  further  functional  resemblance  lies  in  the  part  played  by 
the  labyrinth  in  the  determination  of  posture.  The  resultant  effect 
of  the  impulses  arisir.:^  m  it  is  to  maintain  a  reflex  posture  of  the 
head  and  eyes,  so  that  the  optic  axes  in  a  position  of  rest  are  directed 
towards  the  horizon.  Stimulation  of  the  labyrinth  causes  therefore 
movements  of  the  eyes  which  may  or  may  not  be  associated  with 
correlated  movements  of  the  head. 

As  in  the  case  of  the  other  sense-organs  of  the  anterior  end  of 
the  body,  the  reflexes  excited  from  the  labyrinth  dominate  over 
those  evoked  by  proprioceptive  impulses  from  the  hinder  portions 
of  the  body.  At  the  entry  of  its  nerve  into  the  brain  stem  a  mass 
of  grey  matter  is  developed,  which  must  be  regarded  as  the  head 
ganghon  of  the  proprioceptive  system,  and  the  chief  co-ordinating 
organ  of  all  the  reflex  systems  which  determine  postmc  of  the  limbs 
and  of  the  whole  animal,  and  therefore  the  maintenance  of  equilibrium 


THE  FUNCTIONS  OF  THE  CEREBELLUM  451 

both  at  rest  and  during  locomotion.  This  organ  is  the  cerebellum, 
associated  with  the  grey  matter  in  immediate  connection  with  it 
in  the  upper  part  of  the  fourth  ventricle,  and  situated  at  the  point 
of  entry  of  the  vestibular  nerves.  The  cerebellum  commences  in 
early  foetal  life  as  a  small  elevation  in  the  dorsal  wall  of  the  neural 
tube,  in  close  connection  with  the  point  of  entry  of  the  eighth 
nerve.  Simple  in  structure  and  small  in  extent  in  most  of  the 
fishes  and  amphibia,  it  grows  in  extent  with  increasing  complexity 
of  the  animal's  motor  reactions,  and  attains  its  greatest  develop- 
ment in  the  mammalia.  In  this  class  the  cerebellum,  like  the 
cerebrum,  is  most  highly  developed  in  maiw^niL-ihe— higher  apes. 
It  is  generally  described  in  man  as  consisting..iil_a-«aiddl€  lobe, 
composed  of  the  superior  and  inferior  vermis,  with  two  lateral 
hemispheres,  and  these  are  subdivided  by  anatomists  according  to 
the  situation  of  the  chief  sulci.  From  the  physiological  point  of 
view  the  structure  of  the  organ  is  relatively  simple,  as  is  shown  by 
the  uniformity  of  its  structure  throughout  all  parts.  It  may  be 
considered  as  formed  of  two  main  structures,  viz.  the  cortex  and  the 
central  or  roof  ganglia. 

The  surface  of  the  cerebellum  is  increased  by  being  thrown  into 
folds  or  laminae,  so  that  a  section  of  this  organ  has  a  tree-hke  appear- 
ance. A  section  through  a  lamina  shows  thi'ee  distinct  zones  :  an 
outer  molecular  layer  presenting  a  granular  appearance  with  a  few 
nuclei ;  internal  to  this  a  granule  layer  composed  of  many  nuclei  of 
nerve-cells  ;  and  most  deeply  a  central  core  of  white  matter.  Between 
the  molecular  and  granular  layers  are  situated  the  cells  of  Purkinje, 
large  flask-shaped  cells  each  with  one  apical  dendrite,  distinguished 
above  all  other  dendrites  of  the  central  nervous  system  by  the  richness 
of  its  branching,  and  with  one  axon,  which  leaves  the  base  of  the 
cell  and  passes  down  into  the  central  white  matter,  giving  ofE  collaterals 
in  its  course.  In  preparations  made  by  Golgi's  method  we  are  able  to 
distingmsh  the  various  elements  composing  these  layers  and  their 
relations.  The  molecular  layer,  besides  neurogha-ceUs  and  the 
branching  dendrites  of  the  cells  of  Pm-kinje,  contains  certain  star- 
shaped  cells  (a.  Fig.  201a),  which  give  off  an  axon  running  parallel 
with  the  surface  in  the  molecular  layer.  From  this  axon  branches  dip 
down  towards  the  cells  of  Purkinje,  where  they  end  in  a  rich  basket- 
work  of  fibres  around  the  body  and  beginning  of  the  axon  of  these 
cells".  The  nuclear  or  granular  layer  presents  two  kinds  of  cells. 
The  most  numerous  is  a  small  cell  with  a  few  short  dendrites,  ouch 
of  which  terminates  in  a  claw-shaped  arborisation,  and  a  singlc 
long  axon,  which  passes  straight  up  into  the  molecular  layer,  where 
it  bifurcates.  The  two  branches  run  paiallel  with  the  s\jrfacc  in  a 
direction  at  right  angles  to  the  plane  oi  expansion  of  the  dendriteii 


452 


PnYSIOLOGY 


of  Purkinje's  cells,  apparently  resting  against  the  serrations  on  the 
edges  of  these  processes.  The  second  kind  of  cell  in  the  granular 
layer  is  the  so-called  Golgi's  cell — a  large  cell  with  many  dendrites 
and  an  axon  which  terminates  by  frequent  branches  in  the  neigh- 
bouring grey  matter. 

The  fibres  making  up  the  white  matter  are  of  three  kinds — two 
afferent  and  one  efferent.  The  moss  fibres,  so  called  from  the  curious 
thickenings  they  present  in  the  niiclear  layer,  pass  up  into  the  grey 


Central 
white   - 
matter. 


Fig.  201a.  Schema  of  constituent  elements'of  cerebellum.  (Modified  from  Bohm 
and  Davidoff.)  On  the  left  is  a  section  of  the  cortex  as  it  appears  when 
stained  by  ordinary  methods.  The  middle  portion  represents  diagram- 
matically  a  section  at  right  angles  to  the  laminae,  while  to  the  right  of  the 
dotted  line  the  section  is  taken  in  the  same  plane  as  the  laminae. 

a,  star-shaped  cells  of  molecular  layer  ;  b,  b,  colls  of  Purldnje  ;  c,  '  Golgi 
cell '  ;  d,  small  cells  of  nuclear  layer  ;  e,  '  tendril  fibre  '  ;/,  '  moss  fibre  '  ; 
g,  axon  of  cell  of  Purkinjc. 

matter  and  terminate  by  frequent  branches  in  this  layer.  The 
tendril  fibres^  also  afferent,  end  in  a  rich  arborisation  which  surrounds 
the  distal  part  of  the  bodies  and  the  bases  of  the  dendrites  of  the  cells 
of  Purkinje.  The  effej:gnt_£iires  are  represented  by  the  axons  of  the 
cells  of  ^urkinje^  which  acquire  a  medullary  sheath  and  run  down 
into  the  white  matter. 

This  slight  sketch  of  the  anatomy  gives  us  a  conception  of  the 
extreme  complexity  of  choice  presented  to  nervous  impulses  traversing 
the  cerebellar  cortex.  Thus  a  discharge  along  an  axon  of  the  cell 
of  Purkinjc  may  bo  excited  (1)  by  an  impulse  ascending  the  tendril 


THE  FTTNOTIONS  OF  THE  OEREBELLT^T  453 

fibres ;  or  (2)  by  one  ascending  the  moss  fibres  through  the  granule 
cells,  and  then  passing  by  their  bifurcating  axon  to  the  dendrites 
of  the  cells  of  Purkinje  ;  or  (3)  by  the  star-shaped  cells  of  the  molecular 
layer  and  their  basket-work  round  the  body  of  Purkinje's  cells. 

The  roof  ijdiiglia  consist  of  the  nuclei  fastigii  near  the  middle  line, 
the  nuclei  eniboliformes  situated  just  dorsal  to  these,  and  the  nuclei 
dcntati,  large  crenatcd  capsules  of  grey  matter  lying  in  the  middle 
of  each  lateral  lobe.  The  cells  composing  the  grey  matter  of  the 
central  nuclei  are  large  and  multipolar,  resembling  those  found  in 
the  nuclei  of  motor  nerves. 

The  cerebellum  receives  fibres  from  all  the  receptor  apparatus  of 
the  body  which  can  be  classed  in  the  proprioGeptive  -system.  The 
greater  number  of  tliese  fibres  run  directly  to  the  cortex,  especially 
of  the  vermis,  and  there  is  no  evidence  of  the  passage  of  any  efferent 
fibres  from  the  cortex  directly  to  the  motor  apparatus  of  the  cord. 

The  connections  of  the  cerebellum  are  established  by  means  of 
its  three  peduncles,  and  may  be  classified  as  follows  : 

AFFERENT  TRACTS.  Inferior  Peduncle.  By  this  peduncle 
afferent  fibres  pass  to  the  superior  vermis  : 

(1)  From  Clarke's  column  of  the  same  side  by  the  posterior  cere- 
bellar tract. 

(2)  From  the  dorsal  column  nuclei,  viz.  the  nucleus  gracihs  and 
nucleus  cuneatus  of  each  side,  so  that  connection  is  estabhshed  in 
this  way  with  the  prolongations  of  the  posterior  sensory  roots  which 
run  into  the  posterior  columns  of  the  cord. 

(3)  By  the  internal  restiform  body  from  the  vestibular  division 
of  the  eighth  nerve,  part  of  the  fibxeg_passing  through,  and  perhaps 
making_connections  with.  Deiters^.aiu^leusr"  Fibres  are  also  contri- 
buted from  the  sensory  nucleus  of  the  glossopharyngeal  nerve  in  the 
medulla. 

(4)  A  strong  band  of  fibres  passes  from  the  inferior  olivary  body 
into  the  opposite  cerebellar  hemisphere.  Atrophy  of  one  side  of  the 
cerebellum  induces  a  corresponding  atrophy  in  the  opposite  ohvary 
body. 

Middle  Peduncle.  The  broad  mass  of  fibres  making  up  these 
peduncles  is  partly  afferent  and  partly  efferent.  Many  fibres  originate 
in  the  cells  in  the  formatio  reticularis  of  the  pons,  cross  the  middle 
line,  and  pass  up  into  the  lateral  cerebellar  hemisphere  of  the  opposite 
side.  Fibres  also  pass  from  the  cerebellum  to  the  pons  to  end  round 
cells  in  the  sn,me_region  By  this  means  connection  is  established 
between  the  cerebellar  hemispheres  and  the  gi-ey  matter  of  the  cortico- 
pontine fibres  passing  by  the  crura  cerebri  between  the  pons  and 
the  frontal  and  temporal  portions  of  the  cerebral  cortex  of  the  opposite 
bide.      On  account  of  this  oonnection  there  is  a  close  association 


454 


PHYSTOLOrxY 


between  the  development  of  each  cerebellar  hemisphere  anrl  the 
contralateral  cerebral  hemisphere.  Ati'oph)'  of  one  half  of  the 
cerebrum  brings  about  atrophy  of  the  opposite  hemisphere  of 
the  cerebellum. 

The  Superior  Peduncle.  By  this  path  fibres  from  the  superior 
corpora  quadrigemina,  i.e.  from  the  terminations  of  the  optic  nerve, 
pass  into  the  cortical  grey  matter  of  the  cerebellum  (Fig.  201). 

EFFERENT  TRACTS.  The 
cerebellar  cortex  must  be  regarded 
as  a  receiving  rather  than  as  a 
discharging  station.  Stimulation 
of  it  has  little  effect  unless  strong 
currents  are  employed,  and  a  motor 
response  is  obtained  more  easily 
the  deeper  the  electrodes  are  sunk 
below  the  grey  matter.  The  fibres 
which  form  the  axons  of  the  cells 
of  Purkinje  pass  partly  towards 
the  pons  by  the  middle  peduncle, 
largely,  however,  towards  the  roof 
nuclei,  where  they  terminate.  These 
nuclei  form  the  efferent  stations 
of  the  cerebellum.  From  them 
fibres  pass  in  various  directions. 
A  large  bundle  leaves  the  dentate 
nucleus,  runs  into  the  superior 
peduncle,  or  brachium,  and  passing 
deeply  across  to  the  tegmentum  of 
the  opposite  side,  traverses  the  red 
nucleus  to  end  in  the  subthalamic 
region  of  the  opposite  side  of  the 
brain.  A  certain  number  of  fibres, 
OT,  optic  thalamus ;  rn,  red  nucleus  ;  chiefly  derived    from    the    central 

PCT,    posterior    cerebellar    tract  ;     act,  ,    .  ,  ,  (•-••• 

anterior  cerebellar  tract  ;  v,  fifth  nerve.    UUClei,  JUCh_as  the  nucleus   tastlgU, 

pass  forward  to  the  corpora  quadri- 
gemina chiefly  on  the  same  side.  From  the  cerebellum  itself  no 
direct  tract  runs  into  the  spinal  cord.  The  nuclei  of  Deiters 
and  of  Bechterew,  which  are  connected  with  the  endings  of  the 
vestibular  nerve,  are,  however,  closely  associated  with  the  roof 
nuclei,  and  give  rise  to  descending  fibres  which  pass  into  the 
aiitero-lateral  region  of  the  cord  as  the  vestibulo-spinal  tract. 

The  cerebellum  is  therefore  a  receiving  station  not  only  for  impulses 
which  arise  in  the  skin  and  eyes,  i.e.  on  the  siu-face  of  the  body, 
but  especially  for  those  which  have  been  defined  as  proprioceptive. 


Fig.  202.  Diagram  of  afferent  and 
efferent  tracts  of  cerebellum.  (After 
V.  Gehxjchten.) 


THE  FUNOTION'S  OF  THE  OEREBELLIJM  455 

and  originate  either  in  the  muscles  and  tendons  or  in  tho  labyrinth. 
Activity  of  this  apparatus  is  roused  as  a  rule  by  the  movement  of  the 
ortranism  itself,  and  is  only  a  secondary  result  of  the  environmental 
stimulation  which  provoked  the  original  movement.  By  its  efferent 
tracts  starting  in  the  roof-  and  paracerebellar  nuclei,  the  cerebellum 
is  able  to  affect  the  musculature  of  the  same  side  of  the  body  by 
a  direct  influence  on  the  anterior  horns.  It  also  enters  to  a  much 
greater  extent  into  relation  wnth  the  opposite  cerebral  hemispheres, 
so  that  it  is  in  a  position  to  control  or  modify  the  activity  of  these, 
whether  excited  on  their  sensory  or  on  their  motor  sides. 

The  view  here  laid  down  as  to  the  essential  functions  of  the  cere- 
bellum is  borne  out  by  experiments  involving  stimulation  and  ablation 
of  this  organ. 

STIMULATION  OF  THE  CEREBELLUM.  It  was  first  shown  by 
Ferrier  that  movements  of  the  same  side  of  the  body  can  be  excited 
by  stimulation  either  of  the  cerebellar  hemispheres  or  of  the  superior 
vermis.  These  results  have  been  confirmed  by  subsequent  observers, 
and  point  to  each  half  of  the  cerebellum  being  connected  functionally 
with  the  skeletal  muscular  apparatus  of  the  corresponding  side  of  the 
body.  The  cortex  cerebelh  is  not  excited  with  ease.  To  evoke  move- 
ments much  stronger  stimuli  are  necessary  than,  e.g.  for  the  excitation 
of  the  motor  area  of  the  cerebral  cortex.  This  again  is  in  accordance 
with  what  we  should  expect  from  the  anatomy  of  the  organ,  knowing 
as  we  do  that  the  cortex  is  an  end-station  for  a  number  of  afferent 
paths,  but  has  no  direct  efferent  paths  from  it  to  the  lower  motor 
mechanisms  of  the  cord.  On  the  other  hand,  movements 
are  excited  by  minimal  stimuli  from  the  intrinsic  nuclei  of  the 
cerebellum. 

As  a  result  of  his  experiments  Horsley  has  concluded  that  the 
cortex  cerebelli  must  be  regarded  as  an  afferent  receptive  centre  from 
which  axons  pass  to  the  ventrally  placed  efferent  nuclei,  viz.  the  naclei 
dentati,  fastigii,  emboliformes,  as  well  as  Deiters'  nuclei.  WTiereas 
excitation  of  the  roof  nuclei  producgs  more  especially  movements  of 
the  eyes,  head,  the  paracerebellar  {e.g.  Deiters'  nucleus)  are  responsible 
more  especially  for  the  movements  of  the  trunk  and  limbs.  The 
movements  of  the  body  which  are  thus  evoked  are  those  concerned  in 
maintaining  equilibrium  and  are  involved  in  every  alteration  in  the 
position  of  the  body. 

EFFECTS  OF  ABLATION  OF  THE  CEREBELLUM.  Complete 
unilateral  extirpation  of  the  cerebellum,  after  the  irritation  effects 
of  the  lesion  itself  have  passed  away,  brings  about  a  condition  of 
the  animal  characterised  by  : 

(1)  Slight  loss  of  power  on  the  same  side  of  the  body. 

(2)  Considerable  loss  of  tone  on  the  same  side. 


456  PHYSIOLOGY 

(3)  Tremors  or  rliytlimical  movements  of  the  muscles  on  the  same 
side  accompanying  any  willed  movements. 

These  three  symptoms  are  denoted  by  Luciani  as  asthenia,  atonia, 
and  astasia.  At  first  the  animal  is  quite  unable  to  stand  and  lies 
on  the  side  of  the  lesion  with  neck  and  trunk  curved  in  the  same 
direction  ;  when  it  attempts  to  stand  it  always  falls  to  the  same 
side.     After  two  or  three  weeks  the  power  to  stand  is  regained, 


Sup.Vermis 


,---C.V.T. 


C.R:-: 


..-   .S.C 


Fig.  202a.  Schema  of  connections  of  Deiters'  nucleus.  (Bruce. 
CK,  rcstiform  body  ;  EN,  roof  nuclei ;  SF,  sagittal  fibres  from  cortex  to 
roof  nuclei ;  cvt,  cerebello-vestibular  tract ;  dn,  Deiters'  nucleus  ;  iii,  vi. 
nuclei  of  third  and  sixth  nerves  ;  plf,  posterior  longitudinal  bundle  ;  viii, 
vestibular  division  of  eighth  nerve  ;  sc,  semicircular  canals  ;  vst,  vestibulo- 
spinal fibres. 

though  when  it  attempts  to  walk  the  hindquarters  drag  and^tremors 
and  oscillations  accompany  every  effort.  The  animal  attempts  to 
correct  the  tendency  to  fall  towards  the  side  of  the  lesion  by  an 
exaggerated  abduction  of  the  limbs  to  that  side,  and  is  always  ready 
to  take  advantage  of  the  support  of  a  wall  to  enable  it  to  maintain 
its  equilibrium.  Swimming  is  much  better  carried  out  than  walking, 
the  contact  of  the  water  with  the  skin  furnishing  guidance  to  the 
spinal  mechanism  which  is  lacking  when  the  animal  attempts  to  walk. 
When  the  whole  cerebellum  is  removed  the  animal  is  unable  to 
walk,  sometimes  for  months.     After  a  time  it  gradually  learns  to 


THE  FUNCTIONS  OF  THE  CEREBELLUM  457 

walk,  but  this  is  carried  out  by  an  alteration  of  the  method  of  pro- 
gression. The  disorders  of  locomotion  are  quite  distinct  from  tin- 
spinal  ataxia  observed  aftei'  interference  with  the  afferent  tracts  from 
the  muscles.  The  difficulty  now  is  that  each  diagonal  movement 
of  the  limbs  in  progression  tends  to  throw  the  centre  of  gravity  to 
one  side  or  otlier  of  the  basis  of  support,  and  it  is  tlie  mechanism  for 
maintaining  tlie  right  position  of  the  centre  of  gravity,  i.e.  the  posture 
of  the  body  as  a  whole  in  relation  to  its  environment,  which  is  at  fault. 
The  animal,  in  tlie  case  of  the  dog,  therefore  attempts  to  correct  the 
tendency  to  fall  to  one  side  or  other  at  each  step  by  making  its  basis 
of  support  as  wide  as  possible,  and  gradually  acquires  a  peculiar  gait, 
consisting  of  a  series  of  springs,  in  which  the  two  fore  limbs  and  two 
hind  limbs  act  together,  the  diagonal  movements  of  the  fore  limbs 
being  practically  abandoned. 

In  lesions  of  the  cerebellum  in  man  the  most  marked  symptoms 
are  the  cerebellar  ataxy  and  the  occurrence  of  tremors,  '  astasia,'  on 
the  performance  of  willed  movements.  The  ataxy  has  the  same  origin 
as  that  in  the  dog ;  each  spinal  act  of  locomotion  tends  to  throw 
the  centre  of  gravity  outside  the  line  of  support,  and  the  tendency 
to  fall  thus  brought  about  is  voluntarily  compensated  by  abduction  of 
the  corresponding  limb.  A  staggering  gait  is  thus  produced,  which 
is  practically  identical  with  that  of  a  drunken  man,  and  presents 
no  trace  of  the  over-action  of  muscles  so  characteristic  of  spinal 
ataxy.  That  the  compensation,  which  is  slowdy  acquired  after 
extirpation  of  the  cerebellum,  is  of  cerebral  origin  is  shown  by  the 
fact  that  extirpation  of  the  cerebral  hemispheres,  or  even  of  the 
motor  areas  of  the  hemispheres,  after  extirpation  of  the  cerebellum, 
at  once  abolishes  the  power  of  movement  which  has  been  reac- 
quired, and  after  the  motor  areas  are  destroyed  on  both  sides  the 
loss  of  power  of  progression  is  permanent. 

These  experiments  show  that  the  cerebellum,   in   Sherrington's 
words,  must  be  regarded  as  the  head  ganglion  of  the  proprioceptive 
system,  acting  as  a  centre  where  arrive  the  afferent  impulses  from    i 
the— cord,  the   fifth  nerve,   and  esp^ially-4feffl— ^e>.Jabyrinth.     It  / 
influences,  through  the  superior  peduncle,  the  cerebral  cortex  and  ' 
furnishes  the  subconscious  basis  for  the  guidance  of  the  motor  functions 
of  the  latter  organ.     Through  its  connections  with  the  nticlei  of  the 
bulb  and  the  efferent  tracts  arising  therefrom,  it  augments  the  tonic 
activity  of  all  the  muscles  of  the  body,  an  effecirwhich  is  especially 
marked  in  the  absence  of  the  cerebral  hemispheres  and  is  responsil>lo 
for  the  condition  known  as  decerebrate  rigidity.      As  a  centre  of 
conjunction  for  the  afferent  impressions  from  the  muscles  and  those 
from    the    labyrinth    it    co-ordinates  the    segmental    reflexes,   which 
determine  the  relative  posture  of  each   limb,  with  those  originating 


458  PHYSIOLOGY 

in  the  labyrinth  and  determining  the  position  of  the  head.  Thus 
the  whole  mechanism  provides  for  a  maintenance  of  equilibrium  of 
the  body  as  a  whole,  and  for  the  proper  balancing  of  the  reflex 
movemeutcj  ot  the  different  limbs  with  those  of  the  trunk  during 
all  the  changes  in  the  position  of  the  centre  of  gravity  attending 
locomotion. 

The  view  here  put  forward  really  includes  the  various  descriptions  of  the 
functions  of  the  cerebellum  which  have  been  given  by  different  authorities. 
Thus  Luciani  describes  the  cerebellum  as  an  organ  which  by  unconscious  pro- 
cesses exerts  a  continual  reinforcing  action  on  the  activity  of  all  the  spinal 
centres.  Munk  ascribes  to  the  cerebellum  the  function  of  maintaining  bodily 
equilibrium.  Lewandowsky  regards  the  cerebellum  as  the  central  organ  of 
the  muscular  senses.  Hughlings  Jackson  expressed  many  years  ago  an  important 
characteristic  of  the  cerebellum  when  he  wrote  that  the  cerebellum  is  the  centre 
for  continuous  movements,  and  the  cerebrum  for  changing  movements.  All  these 
descriptions  come  under  Sherrington's  conception  of  the  cerel)ellum  as  head 
ganglion  of  the  proprioceptive  system. 


^Ui,K 


SECTION  XIV 

VISUAL  REFLEXES 

Foremost  among  the  afferent  impulses  determining  the  reactions 
of  higher  animals  are  those  arising  in  the  eyes.  Each  retina,  or  rather 
the  two  retinae  acting  together  as  a  single 
organ,  can  be  regarded  as  a  sensory 
surface,  each  point  of  which  corresponds 
to  a  point,  or  series  of  points,  lying  in 
a  given  direction  outside  the  body. 
Each  optic  nerve  contains  about  half 
a  million  nerve  fibres,  i.e.  as  many  as 
enter  the  cord  by  the  posterior  roots 
from  the  whole  of  the  body.  The  two 
optic  nerves  coming  from  the  retinae 
meet  together  in  the  floor  of  the  fore- 
brain  and  form  the  chiasma.  At  the 
chiasma  a  decussation  of  fibres  takes 
place,  which,  in  animals  such  as  the 
rabbit,  with  no  fusion  of  the  fields  of 
the  two  eyes,  is  practically  complete. 
In  man  only  those  fibres  which  arise  in 
the  mesial  half  of  each  retina  cross  the 
mesial  plane  ;  these,  together  with  the 
uncrossed  fibres  from  the  temporal  half  yig.  203.  Diagram  to  show  con- 
of  the  other  retina,  form  the  optic  tract       nections  of  optic  tracts.    (After 

of  the  opposite  side  (Fig.  203).  The  l.  left,  and  RVright  retina. ;  OD, 
optic   tract   passes  backwards   a<;rOSS   the     optic  decussation  (chiasma) ;  OpT, 

eras  cerebri  and  finally  divides  into  three    «Pj>/>^^^t  '.^'f-  "J!T  Th'^lVfo 

•^  LN,  lenticular  nucleus  ;   In,  optic 

branches,    in    the    roof   of    the    mid-    and     thalamus ;   G,  external  geniculate 

fore-brain,  which  end  in  the  py  matter  "^^^J ^';^::,Z'Sir.:tt 
of  the  anterior  corpora  quadrigemina  and    radiations  running  to  Ot\  the  occi- 

.1  ,  1  •      1   J.     1.    J  J  i.1.       pital  cortex ;  Illn.  nucleus  of  third 

in  the  external  geniculate  body  and  the   ^erve  in  floor  of  Sylvian  aqueduct 
pulvinar  of  the  optic  thalamus.    Running   IV,  fourth  ventricle, 
in  the  optic  tract   are   also  fibres  which 

are  simply  commissural  ;  these  form  the  mesial  root  of  the  optic 
tract.  They  cross  in  the  optic  chiasma  and  .^erve  to  connect  the 
two   internal   geniculate  bodies.      In   addition  to  the   afierent  fibres 

459 


460 


PHYSIOLOGY 


NUCL.  EOlNGEf?. 


NUCt.  LAT.  ANT 
(OARKSCMewlTSCH) 


WUCL.OORS.I.{; 


MUCL.VENT.I.f«NT.)._ 


NUCL.O0P;S.M,(P03T.; 
(V.  G-UDDiNy 


NUCL.  CEMrRALIS-'V 


NUCU.VENT.Ii.fPOST.) 


from   the   retina  to  the  brain  the  optic  tract  contains    a    certain 
number  of  efferent  fibres  which  pass  out  and  end  in  the  retinai. 

It  is  evident  from  these  connections  that  whereas  section  of  one 
optic  nerve,  sav  the  right,  will  only  cause  loss  of  vision  in  the  right 
eye,  section  of  the  right  optic  tract  will  divide  the  fibres  coming 
from  the  right  halves  of  both  retinae.  This  portion  of  the  retina 
in  each  eye  is  stimulated  in  the  normal  position  of  the  eyes  by  rays 
of  light  coming  from  the  objects  lying  to  the  left  of  the  field  of  vision. 
Section  of  the  right  optic  tract  therefore  causes  blindness  to  all 

objects  to  the  left  of  the 
median  line,  left  hemianofia. 
Section  of  both  optic  tracts 
of  course  causes  complete 
blindness. 

Every  movement  of  the 
head  involves  compensatory 
movements  of  the  eyes,  and 
conversely,  in  any  change  in 
the  environment  of  the 
animal  which  demands  its 
attention,  there  is  a  move- 
ment of  the  eyes  so  as  to 
turn  the  gaze  on  to  the 
%M/  origin  of  the  disturbance  as 
an  antecedent  to  any  body 
movement.  In  the  absence 
of  normal  regulative  im- 
pulses from  the  skin,  or  from 
Fio.  204.  Diagram  to  show  origin  of  the  different  ^}^q  semicircular  canals,  the 
fibres  of  the  third  and  fourth  nerves  from  the  .  .  . 

oculo-motor  nuclei.  afterent    impressions     from 

the  eyes  may  serve  for  the 
maintenance  of  fairly  well  co-ordinated  movements — a  compensa- 
tion which  is  rendered  possible  by  the  power  of  the  cerebral  cortex 
to  learn  new  reactions  by  experience. 

The  centres  for  the  eye  movements  are  contained  in  the  grey 
matter  in  the  floor  of  the  back  part  of  the  third  ventricle  and  of  the 
iter  of  Sylvius.  Here  we  find  the  nucleus  of  the  third  or  oculo-motor 
nerve.  The  oculo-motor  nucleus  consists  of  several  divisions,  viz. 
a  lateral  part  containing  large  motor  cells,  a  superficial  median 
nucleus  with  small  cells,  and  a  deeper  median  nucleus  with  large  cells. 
By  localised  stimulation  it  has  been  found  possible  to  differentiate 
the  functions  of  the  different  parts  of  the  nucleus  (Fig-  204).  Stimula- 
tion of  the  back  part  of  the  third  ventricle  causes  contraction  of  the 
ciliary  muscles,  and  a  little  behind  this  contraction  of  the  pupil 


VISUAL  REFLEXES 


461 


Oil  stimulating  the  floor  of  the  iter,  from  before  backwards  we  obtain 
contractions  in  order  of  the  rectus  internus,  the  rectus  superior,  the 
levator  palpebrae  superioris,  the  rectus  inferior,  and  the  inferior 
oblique  muscle.  On  stimulating  more  laterally,  or  exciting  the 
corpora  quadrigemina,  dilatation  of  the  pupil  was  obtained. 


Ani.C.Quad. 


o.c.m.n. 


Optic  Tract 


Vlll.Vesf.n 
^est  spin,  tract. 


Ant '^ basis  bundle 


Fig.  205.     Diagram  of  oonnections  of  posterior  lougitudinal  l)iin<ili\ 
Ant.C.Quad,    anterior   corpus    quadrigemimim  ;      oc.iu.n,  oculo  -  motor 

inicleiis  ;   IV.n,  nucleus  of  fourth  nerve  ;   VT.n.  nucleus  of  sixth   nerve  ; 

D.N,  Deiters' nucleus  ;   S.O,  superior  olive;  VIII. Vest. n.  vestibular  nerve; 

p.l.b,  posterior  longitudinal  bundle  ;   Ist  c.n,  first  cervical  nerve. 

It  seems  probable  that  the  optic  thalamus  and  the  closely  relatod 
external  giMiiculate  body  arc  mainly  concerned  with  the  reception 
of  visual  impulses  and  their  forwarding  to  the  cerebral  cortex.  On 
the  other  liand,  the  anterior  (tr  .superior  corpora  quadrigemina  are 
mainly  concerned  with  the  co-ordination  of  visual  impresv^^ions  and 
visual  movements  with  the  movements  of  every  part  of  the  body, 


462  PHYSIOLOGY 

and  especially  with  the  complex  mechanism  we  have  already  studied 
in  connection  with  the  labyrinth  and  cerebellum.  Stimulation  of 
the  corpora  quadrigemina  therefore  evokes  movements  of  the  eyes 
and  of  the  head  ;  extirpation  of  this  part,  though  it  may  interfere 
with  co-ordination,  does  not  necessarily  involve  loss  of  sight,  even 
when  the  extirpation  is  bilateral. 

The  multifarious  intercourse  which  is  continually  taking  place 
between  the  eye  centres  and  those  for  the  movements  of  the  body, 
and  between  afferent  impressions  from  the  eyes  and  those  from  the 
semicircular  canals  and  the  proprioceptive  system  generally,  is 
efiected  to  a  large  extent  through  the  intermediation  of  the  posterior 
longitudinal  bundle,  which  extends  throughout  the  whole  length 
of  the  mid-brain  and  the  hind-brain,  and  in  the  spinal  cord  becomes 
continuous  with  the  anterior  basis  bundle  of  the  anterior  columns. 
Receiving  fibres  above  through  the  anterior  commissure  from  the 
optic  thalamus,  and  from  the  superior  corpora  quadrigeminal  bodies, 
it  is  associated  in  its  course  with  the  three  motor  nuclei  that  give 
origin  to  the  nerves  supplying  the  muscles  of  the  eyeball,  viz.  the 
third,  foui'th,  and  sixth  nerves.  Fibres  enter  the  posterior  longi- 
tudinal bundle  from  the  auditory  system,  from  the  facial  nucleus, 
and  from  the  superior  olive,  and  connections  are  also  established 
between  this  bundle  and  the  nucleus  of  Deiters,  representing  the 
central  station  of  impulses  from  the  labyi'inth.  The  general  con- 
nections of  the  bundle  are  shown  in  Yin.  205. 


SECTION  XV 

SUMMARY  OF  THE  CONNECTIONS  AND  FUNCTIONS 
OF  THE  CRANIAL  NERVES 

Cranial  nerves.  The  cranial  nerves  are  generally  reckoned  as 
twelve  in  number  :  1st,  olfactory  ;  2nd,  optic  ;  3rd,  oculo-motor  ; 
4tli,  or  trochlear  ;  5th,  or  trigeminus  ;  6th  ;  7th,  or  facial ;  8th, 
auditory  ;  9th,  glossopharyngeal  ;  10th,  vag-us  or  pneumogastric  ; 
11th,  spinal  accessory  ;   12th,  hypoglossal. 

Of  these  the  first  two  stand  on  a  different  footing  from  the  rest, 
which,  like  the  spinal  nerves,  are  outgxoAvths  of  nerve  fibres  from 
the  central  tube  of  grey  matter  surrounding  the  neural  canal  or  from 
ganglia  corresponding  to  the  spinal  posterior  root  ganghon. 

The  olfactory  bulb  and  the  retina?,  from  which  the  majority  of 
the  fibres  forming  the  olfactory  tract  and  the  optic  nerve  respectively 
take  their  origin,  are  analogous  rather  to  lobes  of  the  brain  than  to 
peripheral  sense-organs.  Thus  in  the  retina  there  are  three  relays 
of  nem-ons  through  which  the  visual  impulse  must  pass  before  it 
arrives  at  the  optic  nerve.  The  olfactory  tract  and  optic  nerve  are 
thus  comparable  with  the  association  or  commissm-al  fibres  connecting 
different  parts  of  the  central  nervous  system.  The  connections  of 
these  sensory  fibres  have  abeady  been  fully  dealt  with,  and  the 
structure  of  the  peripheral  sense-organ  will  be  treated  of  under  the 
physiology  of  the  special  senses.  Among  the  cranial  nerves  proper 
we  may  therefore  reckon  the  third  to  the  twelfth. 

The  third  or  oculo-motor  arises  from  an  extensive  nucleus  which 
extends  on  either  side  along  almost  the  whole  length  of  the  ventral 
part  of  the  aqueduct  of  Sylvius  close  to  the  middle  line,  the  most 
anterior  part  lying  in  the  back  part  of  the  third  ventricle  (Fig.  204). 
The  anterior  part  is  com})()sed  of  small  cells  which  give  origin  to  the 
fibres  innervating  the  intrinsic  muscles  of  the  eye,  namely,  the  ciliary 
muscle  and  the  sphincter  pupilla\  The  rest  of  the  nucleus  is  made 
up  of  large  multipolar  cells,  arranged  in  groups,  and  gives  origin 
to  the  fibres  passing  to  most  of  the  extrinsic  muscles  of  the  eye.  The 
fibres  of  the  third  nerve  pass  through  the  tegmentum  to  emerge 
at  the  inner  margin  of  the  crusta  of  the  same  side.  The  fibres  from 
the    posterior    large-celled    nucleus    supply    the   following    muacles  : 

463 


464  PHYSIOLOGY 

levator  palpebrarum,  superior  rectus,  inferior  rectus,  internal  rectus, 
and  inferior  oblique. 

Stimulation  of  the  trunk  of  the  third  nerve  causes  the  eyeball 
to  look  upwards  and  inwards,  with  contraction  of  the  pupil  and 
spasm  of  accommodation.  By  careful  stimulation  of  various  parts  of 
its  nucleus  the  different  movements  of  this  muscle  may  be  produced 
separately. 

The  nucleus  of  the  fourth  nerve  is  situated,  just  behind  that  for 
the  third,  in  the  floor  of  the  Sylvian  aqueduct,  on  a  level  with  the 
inferior  corpora  quadrigemina.  The  fibres  run  from  here  down 
towards  the  pons,  then  turn  sharply  backwards  to  pass  into  the 
valve  of  Vieussens,  which  they  cross  horizontally,  decussating  with 
the  nerve  of  the  opposite  side.  The  superficial  origin  is  therefore 
^rom  the  valve  of  Vieussens,  the  thin  plate  of  grey  matter  which 
forms  the  roof  of  the  fourth  ventricle  just  in  front  of  the  cere- 
bellum. This  nerve  supplies  the  superior  oblique  muscle  of  the 
eyeball.  Its  stimulation  causes  the  eyeball  to  look  downwards  and 
inwards. 

The  sixth  nerve,  the  motor  nerve  for  the  external  rectus  muscle 
of  the  eyeball,  arises  from  a  group  of  large  multipolar  cells  lying 
on  each  side  of  the  middle  line  in  the  floor  of  the  fourth  ventricle 
in  its  upper  part.  The  fibres  of  the  nerve  pass  directly  outwards  to 
emerge  from  the  anterior  ventral  surface  of  the  medulla  between 
the  p3rramids  and  the  olivary  eminence,  at  the  lower  border  of  the 
pons.  Stimulation  of  this  nerve  causes  the  eyeball  to  look  directly 
outwards.  All  these  three  oculo-motor  nuclei  receive  collaterals 
from  the  longitudinal  fibres  forming  the  posterior  longitudinal  bundle, 
many  of  which  are  axons  of  cells  in  Deiters'  nucleus.  It  is  by  this 
means  that  the  contractions  of  the  muscles  moving  the  eyeball  are 
co-ordinated.  Sherrington  has  shown  that  although  the  third,  fourth, 
and  sixth  nerves  arise  directly  from  the  brain  stem  and  have  no 
ganglion  on  their  course,  they  are  really  mixed  afferent- efferent 
nerves.  Their  afferent  fibres,  which  must  arise  from  the  cells  in  the 
centra]  nervous  system  itself,  run  to  the  receptor  nerve-endings 
with  which  all  the  extrinsic  eye  muscles  are  richly  provided.  They 
are  exclusively  proprioceptive,  and  supply  no  organs  outside  the 
muscles  innervated  by  the  motor  fibres.  The  occurrence  of  afferent 
fibres  in  these  nerves  explains  the  fact  previously  observed  by  Sher- 
rington, that  after  total  desensitisation  of  the  eyeball  by  means  of 
cocaine,  or  by  section  of  the  first  division  of  the  fifth  nerve,  the  ocular 
movements  are  carried  out  with  as  much  precision  as  in  the  normal 
animal.  As  we  have  seen,  such  precision  of  movement  requires  the 
co-operation  of  afferent  impressions  from  the  muscle,  and  the  only 
possible  channels  for  these  impressions  are  the  proprioceptive  sense- 


CONNECTIONS  AND  FUNCTIONS  OF  CRANIAL  NERVES  465 

organs  and  the  afferents  of  the  third,  fourth,  and  sixtli  nerve  pairs 
themselves. 

The  fijth  nerve,  or  trigeminus,  resembles  a  spinal  nerve  in  that 
it  has  a  motor  as  well  as  a  sensory  root.  The  motor  root  is  much 
the  smaller  of  the  two.  The  fibres  of  the  sensory  root  take  their 
origin  in  the  cells  of  the  Gasserian  ganglion,  which  is  in  all  respects 
similar  to  the  ganglion  of  a  posterior  spinal  nerve-root.  The  sensory 
root  represents  the  somatic  afferent  part  of  all  the  motor  cranial 
nerves  from  the  third  to  the  hypoglossal  and  has  a  correspondingly 
wide  field  of  ending  in  the  brain  stem.  The  afferent  fibres  of  the 
fifth  nerve,  as  they  enter  the  pons,  bifurcate,  like  a  spinal  afferent 
nerve,  into  ascending  and  descending  branches.  The  ascending 
branches  are  short  and  pass  to  an  upper  sensory  nucleus,  situated 
below  the  lateral  part  of  the  fourth  ventricle  in  the  upper  part  of  the 
pons.  The  descending  branches,  which  are  much  longer,  are  collected 
into  one  or  more  bundles  which  pass  downwards  in  the  lateral  pait 
of  the  reticular  formation,  accompanied  by  the  downward  extension 
of  the  sensory  nucleus  known  as  the  substantia  gelatinosa.  The 
descending  root  can  be  traced  down  in  the  upper  part  of  the  cervical 
cord,  its  fibres  in  this  region  forming  a  cap  to  the  gelatinous  substance 
of  Rolando.  From  the  cells  of  the  sensory  nucleus  fibres  pass  towards 
the  median  raphe,  crossing  to  the  other  side  to  take  part  in  the 
formation  of  the  tract  of  the  fillet  (the  trigemino- thalamic  tract). 
The  efferent  fibres  forming  the  motor  root  arise  from  two  nuclei. 
The  chief  motor  nucleus  consists  of  large  pigmented  multipolar  cells 
situated  just  below  the  surface  of  the  lateral  margin  of  the  fourth 
ventricle  at  the  upper  part  of  the  pons.  The  accessory  or  mesence- 
phalic nucleus  is  composed  of  large  unipolar  cells,  situated  in  the 
central  grey  matter  along  the  lateral  aspect  of  the  anterior  end  of  the 
fourth  ventricle,  and  in  a  corresponding  position  in  the  mid-brain  as 
far  as  the  upper  border  of  the  inferior  corpora  quadrigemina. 

The  fifth  nerve  is  the  motor  nerve  for  the  muscles  of  mastication, 
and  for  the  tenaoiL^mpani  and  tensor  jjalati  muscles.  It  is  the 
sensory  nerve  for  the  whole  of  the  face  (including  eyeball,  mouth, 
and  nose).  It  also  contains  dilator  fibres  to~~fetou"d^essels  derived 
fromlTie  chorda  tympani,  and  is  said  to  have  trophic  functions.  The 
latter  conclusion  is  from  the  fact  that  section  of  the  fifth  nerve  in  the 
skull  is  followed  by  ulceration  and  sloughing  of  the  cornea,  and 
finally  by  destructive  changes  involving  the  whole  eyeball.  Since, 
however,  these  results  may  be  prevented  by  carefully  shielding  the  eye 
from  all  dust  and  deleterious  influences,  it  is  probable  that  the  ulcera- 
tion is  merely  a  secondary  consequence  of  the  anaesthesia.  The  cornea 
being  ana3stheti"c,  foreign  objects  that  fall  on  its  surface  are  allowed 
to  remain  there,  and  so  give  rise  to  injurious  changes  and  ulceration. 

30 


466  PHYSIOLOGY 

The  fifth  is  also  said  to  be  the  nerve  of  taste  for  the  anterior  third 
of  the  tongue,  but  it  is  probable  that  the  taste  fibres  which  run  in 
the  fifth  are  derived  from  the  glossopharyngeal  or  from  the  nervus 
intermedins. 

The  eighth  nerve  and  its  connections  have  been  discussed  already 
on  several  occasions.  We  may  here  briefly  summarise  what  has  already 
been  stated.  In  describing  the  eighth  nerve  it  is  necessary  to  consider 
separately  its  two  divisions,  the  dorsal  or  cochlear  division  and  the 
ventral  or  vestibular  nerve.  The  fibres  of  the  cochlear  nerve  originate 
in  the  bipolar  cells  of  the  spiral  gangUon  of  the  cochlea.  They  carry 
impulses  from  the  auditory  end-organ.  On  entering  the  medulla  they 
bifurcate  into  ascending  and  descending  branches  which  terminate  in 
two  nuclei,  the  ascending  branches  in  the  ventral  nucleus,  the  descend- 
ing branches  in  the  dorsal  nucleus.  The  ventral  or  accessory  nucleus 
lies  between  the  cochlear  and  vestibular  divisions  ventrally  to  the 
restiform  body.  The  dorsal  nucleus,  often  called  the  acoustic  tubercle, 
forms  a  rounded  projection  on  the  lateral  and  dorsal  aspects  of  the 
restiform  body.  From  these  two  nuclei  new  relays  of  fibres  start,  pass 
to  the  other  side,  and  cross  the  median  raphe  (where  they  form  the 
trapezium)  to  run  up  in  the  lateral  fillet  of  the  opposite  side.  From 
the  ventral  nucleus  the  fibres  pass  directly  to  the  opposite  side,  forming 
the  greater  part  of  the  trapezium,  making  connection  on  their  way  with 
the  nucleus  of  the  trapezium  and  with  the  superior  olive.  From  the 
dorsal  nucleus  most  of  the  axons  pass  dorsally,  forming  the  striae 
acousticse  at  the  middle  of  the  floor  of  the  fourth  ventricle.  On 
arriving  at  the  middle  line  they  dip  down  and  join  the  fibres  of  the 
trapezium  of  the  opposite  side.  The  further  course  of  these  fibres 
up  to  the  internal  geniculate  body,  the  posterior  corpora  quadrigemina, 
and  the  auditory  radiations  of  the  cerebral  cortex,  have  been  described 
on  p.  436. 

The  ventral  division  of  the  eighth  nerve,  or  vestibular  nerve,  origi- 
nates in  the  bipolar  cells  of  the  vestibular  ganglion  or  ganglion  of 
Scarpa.  These  cells,  like  those  of  the  spiral  ganglion,  retain  the  primi- 
tive bipolar  character.  The  fibres  divide  into  ascending  and  descend- 
ing branches  which  become  connected  with  two  nuclei.  The  dorsal 
or  vestibular  nucleus,  or  principal  nucleus,  which  receives  the  ascending 
fibres,  is  a  mass  of  ^rey  matter  lying  laterally  of  the  vago-glosso- 
pharyngeal  nucleus  and  corresponding  to  the  lateral  triangular  area, 
the  trigonum  acoustici,  which  is  seen  on  the  surface  of  the  fourth 
ventricle  outside  the  ala  cinerea.  The  descending  vestibular  nucleus, 
receiving  the  descending  branches  of  the  vestibular  nerve,  lies  below 
but  continuous  with  the  principal  nucleus.  The  fibres  of  the  vestibular 
nucleus  send  also  collaterals  to  the  nucleus  of  Deiters  and  the  nucleus 
of    Bechterew,   two  accumulations  of    large    multipolar  cells  lying 


J 


CONNECTIONS  AND  FUNCTIONS  OF  CRANIAL  NERVES   iCu 

ventrally  and  internally  to  the  vestibular  nucleus,  bcjtli  nuclei  being  in 
close  relation  to  the  roof  nuclei  of  the  cerebellum.  Many  fibres  of  the 
vestibular  nerve  pass  apparently  through  these  various  nuclei  on  the 
inner  side  of  the  restiform  body  into  the  cerebellum,  where  they  make 
connection  with  the  roof  nucleus  or  nucleus  fastigii.  By  the  nuclei  of 
Deiters  and  Bechterew  the  vestibular  nerve  is  connected  through  the 
dorsal  longitudinal  bundle  and  the  descending  vestibulo-spinal  tract 
with  the  motor  nuclei  of  the  cranial  and  spinal  nerves. 

The  use  of  the  vestibular  nerve  is  entirely  connected  with  the 
function  of  equilibrium.  It  is  probably  not  concerned  in  conveying 
auditory  impressions,  all  its  nerve  fibres  being  derived  ultimately 
from  the  nerve-endings  in  the  saccule  and  utricle  and  semicircular 
canals. 

The  seventh  cranial  nerve  or  facial  nerve  emerges  from  the  brain 
at  the  inferior  margin  of  the  pons,  lateral  to  the  point  of  exit  of  the 
sixth  nerve.  It  is  almost  entirely  a  motor  nerve,  but  carries  also 
some  sensory  fibres  for  taste  and  general  sensibility  which  it  receives 
from  the  nerviis  intermedius  of  Wrisberg.  The  motor  nucleus  of 
the  seventh  nerve  lies  in  the  reticular  formation,  dorsally  to  the 
superior  olive,  at  some  depth  below  the  floor  of  the  fourth  ventricle. 
From  this  nucleus  the  fibres  first  pass  inwards  and  dorsally  towards 
the  floor  of  the  ventricle,  where  they  collect  to  form  a  bundle  which  runs 
upwards  in  the  grey  matter  for  a  short  distance  and  then  turns  sharply 
in  a  ventro-lateral  direction  to  emerge  on  the  lateral  aspect  of  the  pons. 
The  fibres  from  the  motor  nucleus  supply  the  muscles  of_the_face,  the 
scalp,  and  the  ear.  Secretory  fibres  also  run  in  the  chorda  tympani. 
which  is  a  branch  of  the  facial.  These,  however,  are  probably  derived, 
like  the  sensory  fibres,  from  the  nerve  of  Wrisberg.  The  sensory 
fibres  of  the  nerve  of  Wrisberg  originate  in  the  nerve-cells  of  the  genicu- 
late ganglion,  and,  passing  inwards  with  the  main  root  of  the  facial, 
divide  into  ascending  and  descending  branches  and  end  in  the  upper 
part  of  the  column  of  grey  matter  which  receives  also  the  sensory  fibres 
of  the  ninth  and  tenth  cranial  nerves. 

The  nitith  and  tenth  cranial  nerves  arise  by  a  series  of  bundles  of 
nerve  fibres  from  the  side  of  the  medulla.  Both  the  ninth  and  tenth 
are  mixed  visceral  sensory  and  motor  nerves.  The  sensory  nucleus 
is  a  column  of  grey  matter  lying  laterally  to  the  hypoglossal  nucleus 
just  below  the  prominence  on  the  floor  of  the  fourth  ventiicle  known 
as  the  ala  cinerea.  The  descending  fibres  of  these  nerves  form  a 
well-marked  bundle  of  white  fibres  known  as  the  fasciculus  solitarius. 
or  sometimes,  from  its  supposed  connection  with  the  regulatirn  of 
respiration,  the  '  respiratory  bundle  of  Gierke.'  It  may  be  traced  down 
as  far  as  the  uppermost  part  of  the  cervical  cord,  its  fibres  losing  them- 
selves on  their  way  down  among  the  cells  of  the  enclosing  grey  matter. 


468 


PHYSIOLOGY 


The  efferent  fibres  of  the  ninth  and  tenth  nerves  are  derived  partly 
from  the  dorsal  nucleus  of  the  va<ius  and  accessory  nerves  lying 
externally  to  the  nucleus  of  the  twelfth  nerve,  and  partly  from  the 
nucleus  ambiguus,  a  mass  of  grey  matter  lying  deeper  in  the  medulla 
(Fig.  206). 

The  ninth  or  glossojiharyngeal  nerve  supplies  motor  fibres  to  the 
muscles  of  the  pharynx  and  the  base  of  the  tongue,  and  secretory 
fibres  to  the  parotid  gtad.  The  sensory  fibres  convey  impulses  from 
the  tongue,  the  moutETand  pharynx,  the  fibres  originating  outside 
the  central  nervous  system  in  the  ganglion- cells  of  the  ganglion 
petrosum  and  the  ganglion  superius.  It  also  contains  inhibitory 
fibres  to  the  respiratory  centre. 


Fig.  200.  Plan  of  the  origin  of  the  tenth  and  twelfth  nerves. 
pyr,  pyramid ;  nXII,  nucleus  of  hypoglossal ;  XII,  hypoglossal  nerve  ; 
dnX,  XI,  dorsal  nucleus  of  vagus  and  accessory  ;  n.amb,  nucleus  ambiguus  ; 
fs,  fasciculus  solitarius  (descending  root  of  vagus  and  glossopharyngeal)  ; 
fsn,  its  nucleus  ;  X,  crossing  motor  fibre  of  vagus  ;  g,  cell  in  ganglion  of 
vagus  giving  origin  to  a  sensory  fibre  ;  dV,  descending  root  of  fifth  ;  cr, 
corpus  restiforme. 

The  tenth  nerve,  vayus  or  pneumogastric,  is  joined  by  the  accessory 
part  of  the  spinal  accessory,  so  that  the  two  nerves  may  be  con- 
sidered together.     It  has  both  afferent  and  efferent  functions. 
Efferent  functions  : 

Motor  to  levator  palati  and  three  constrictors  of  pharynx. 

Motor  to  muscles  of  larynx. 

Inhibitory  to  heart. 

Motor  to  muscular  walls  of   oesophagus,  stomach,   and  small 

intestine. 
Motor  to  unstriated  muscle  in  walls  of  bronchi  and  bronchioles. 
Secretory  to  glands  of  stomach  and  possibly  to  pancreas. 


CONNECTIONS  AND  FUNCTIONS  OF  (.'RANIAL  NP:RVES   4()<) 

Afferent  functions  : 

Regulate  respiration.     Stimulation  of  central  end  may  quicken 
respiration  and  promote  inspiration,  or  may  inhibit  inspiration. 
Stimulation  of  central  end  of  superior  laryngeal  branch  causes 
stoppage  of  inspiration,  expiration,  cough. 
Depressor  and  pressor  (from  heart  to  vaso-motor  centre). 
Reflex  inhibition  of  heart. 

Its  afferent  fibres  arise  from  cells  in  the  gangha  on  the  trunk  of 
the  vagus,  namely,  the  jugular  ganglion  and  the  ganglion  trunci  vagi. 
The  spinal  accessory  nerve  arises  partly  in  connection  with  the  vagus, 
partly  by  a  series  of  roots  from  the  lateral  region  of  the  spinal  cord  as  low 
as  the  sixth  cervical  segment.  The  spinal  portion  of  the  nerve  is  purely 
motor  and  supplies  fibres  to  the  sterno-mastoid  and  trapezius  muscles. 

The  twelfth  or  hypoglossal  nerve  arises  from  a  collection  of  large 
multipolar  cells  in  the  floor  of  the  fourth  ventricle  at  its  lower  end  close 
to  the  middle  line.  The  nerve-trunk  issues  from  the  ventral  part  of 
the  medulla  in  the  groove  between  the  anterior  pyramid  and  the 
olivary  body.  The  hypoglossal  isjpurely  motor  in  function,  supplying 
the  muscles  of  the  tongue,  the  extrinsic  muscles  of  the  larynx,  as  well 
as  those  moving  the  hyoid  bone. 

Since  the  integrity  of  the  nuclei  of  the  cranial  nerves  is  a  necessary 
siDndition  for  the  carrying  out  of  various  reflex  acts  in  which  these 
nerves  are  involved,  the  gTey  matter  of  the  fourth  ventricle  and  aque- 
duct is  often  spoken  of  as  if  it  were  cut  up  into  a  series  of  centres  distinct 
for  every  act.  The  chief  of  these  are  the  respiratory  and  the  vase- 
motor  centres.     Other  centres  that  may  be  enumerated  are  : 

Centres  for  movements  of  intrinsic  and  extrinsic  ocular  muscles. 
•   Cardiac  inhibition. 

Mastication,  deglutition. 

Sucking. 

Convulsive  (connected  with  respiratory). 

Vomiting. 

Diabetic  (connected  with  vaso-motor). 

Salivary. 

Centres  of  phonation  and  articulation. 

We  shall  have  to  consider  the  action  of  these  centres  more  fully  in 
treating  of  the  several  functions  of  the  body.  It  must  be  remembered, 
however,  that  when  a  dozen  or  more  centres  are  enumerated  as  being 
situated  in  the  fourth  ventricle,  it  is  not  meant  that  we  can  anatomi- 
cally distinguish  a  group  of  cells  for  each  act  or  group  of  actions 
named.  When  we  say  that  a  part  of  the  nervous  system  is  a  centre 
for  any  action,  we  merely  mean  that  this  part  forms  a  necessary  link,  or 
meeting  of  the  ways,  in  the  complicated  directing  of  norvo  impulses 
that  takes  place  in  every  co-ordinated  act. 


THE   CEREBRAL    HEMISPHERES 

SECTION  XVI 

GENERAL  STRUCTURAL  ARRANGEMENTS  OF 
THE  CEREBRUM 

The  cerebral  hemispheres  form  the  most  important  part  of  the 
brain.  It  is  to  the  development  of  this  part  that  is  due  the  rise  in 
type  in  vertebrates.  In  development  they  are  formed  as  two  diverti- 
cula from  the  front  part  of  an  outgrowth  of  the  first  cerebral  vesicle. 


Fig.  207. 


Section  through  cerebral  cortex  of  the  frog. 
(After  Edinger.) 


In  the  lowest  vertebrates  these  outgrowths  are  connected  entirely  with 

the  olfactory  sense-organs,  and  we  may  regard  the  olfactory  part  of  the 

brain  as  a  fundamental  part  on  which  has  been  built  up  all  the  rest  of 

the  cerebral  hemispheres.      In  a  cartilaginous  fish  the  whole  of  the 

upper  brain  is  connected  with  the  organ  of  smell,  and  consists  of  a 

thickening  in  the  floor  of  the  outgrowth  from  the  fore-brain  to  which 

is  attached  in  front  the  olfactory  lobe.     The  roof  of  the  outgrowth 

is  formed  of  simple  epithelium.     With  the  development  of  the  visual 

sensations  in  the  bony  fishes  there  is  still  very  little  corresponding 

growth   of    the  fore-brain,  most  of  the  fibres  from  the  optic  nerves 

going  to  the  roof  of  the  mid- brain  (the  optic  lobes).     The  beginning 

of  the  cerebral  hemispheres  is  associated  with  the  development  of 

nervous  tissue  in  the  roof  of  the  prosencephalon.     At  its  first  appearance 

this  higher  brain  material  still  receives  chiefly  olfactory  impressions. 

But  the  structure  of  the  cerebral  cortex  thus  laid  down  differs  from 

470 


STRUCTURAL  ARRANGEMENTS  OF  CEREBRUM       471 

that  of  the  centres  forming  the  brain  stem  or  the  olfactory  lobe  itself 
in  that  it  provides  for  a  very  rich  association  of  impulses  between  all  its 
parts.  The  fibres  entering  the  cortex  break  up  into  a  fine  meshwork 
of  fibres  which  run  tangentially  to  the  surface  and  come  in  contact 
with  innumerable  dendrites  of  nerve-cells  situated  at  some  little  dis- 
tance below  the  surface  (Fig.  207).  We  have  here  the  first  germ  of 
an  apparatus  in  which  the  nerve-paths  can  be  determined  by  education, 
i.e.  in  consequence  of  past  inhibitions  by  pain,  rather  than  by  the 
limits  set  by  heredity.  In  the  amphibian  brain,  and  still  more  in  the 
brain  of  the  reptile,  the  cerebral  cortex  extends  over  the  whole  of  the 
roof  of  the  cerebral  hemispheres,  though  even  here  a  very  large  pro- 
portion of  it  is  devoted  to  the  association  of  olfactory  impulses.  The 
importance  of  these  olfactory  association  fibres  is  well  shown  in  the 


Fig.  208. 


Schematic  section  through  lirain  of  lizard  showing  the  chief 
nerve-tracts.     (After  Edinger.) 


figure  (Fig.  208)  of  a  diagrammatic  section  through  a  lizard's  brain. 
Above  the  reptiles  there  is^  divergence  in  the  course  of  development. 
The  wider  reactive  powers  of  birds  are  based  chiefly  on  an  enormous 
development  of  the  corpus  striatum,  whereas  in  mammals  the  corpus 
striatum  remains  relatively  small  and  the  chief  development  occurs 
in  the  roof  of  the  cerebral  hemispheres,  the  so-called  pallium  or  mantle. 
With  the  increased  entry  of  fibres  from  the  optic  thalamus  into  the 
cerebral  hemispheres,  carrying  impulses  from  the  eyes,  ears,  and  all 
the  other  sense-organs  of  the  body,  the  olfactory  part  of  the  brain 
diminishes  in  importance,  and  in  the  higher  mammal  and  man  is  alto- 
gether overshadowed  by  the  newly  formed  part  of  the  pallium.  On 
this  account  those  parts  of  the  cerebral  hemispheres  in  special  connec- 
tion with  the  olfactory  sense-organs  are  often  spoken  of  as  the  archi- 
pallium,  in  distinction  to  all  the  rest  of  the  more  newly  formed  brain 
substance,  known  as  the  neopallium. 

In  man  the  cerebral  hemispheres  form  a  great  ovoid  mass  exceeding 


S.precentralis  Inferior       Snreeentratis  superior 
......  I  ,    S. centralis  (Rolandi) 

S.fronUlis  inferior  5. postcentralis  inferior 

S.frontalis  superior  ,  ■^^^^'^T''^.^.^::^^^^        S.postcentralis  mtemiedius 

\^  -t^St'lJ*^---*^-'''^       ^^      Wt    y^^^^^tj^y      S.  postcentralis  superior 

S.intraparietalis 


5. frontalis  medius 


Ramus 
Bnt.horizontalis 
'  Ramus  sntascendins 
5.  diagonalis 

Ramus  post,  of  Sylvian  f.      ' 


S.iemporalis  medius 


5  occipitalis  lateralis 

S. occipitalis  transi/ersus 


Fig.  209a.     Left  cerebral  hemisphere  of  man,  lateral  aspect.     (Symington.) 


S.precentralis  mesialis 

S. centralis  (Rolandi ) 

Pars  marainalis  s.cinduli 

Sparietalis  superior 
S.pariete  -occipitalis 


5.  cinduli 


Scqrpori'i  callosl 


5.  rostral  IS 

-.cisura  temporalis 


5.  ca  tear  in  us 


5. '-  bpariet^lis 


S  collate  alls 
5  temporalis  infer/or 


Fascia  denfata 


Fig.  209b.     Left  cerebral  hemisphere  of  man,  fiom  the  mesial  aspect.     (SyMiNGTON.) 


STRUCTURAL  ARRANGEMENTS  OF  CEREBRUM       473 

in  size  all  the  rest  of  the  brain  put  together.  The  two  hemispheres  are 
separated  by  a  deep  fissure,  the  great  longitudinal  fissure.  Before  and 
behind,  this  fissure  extends  to  the  base  of  the  cerebrum,  but  in  the 
middle  the  two  hemispheres  are  connected  by  a  mass  of  transverse 
fibres  known  as  the  corpus  callosum.  On  the  outer  side  each  cerebral 
hemisphere  presents  a  deep  cleft,  the  Sylvian  fissure.  The  whole 
surface  of  the  brain  is  thrown  by  fissures  into  convolutions,  by  which 
means  a  very  large  increase  of  the  surface  grey  matter  is  obtained. 
By  these  fissures  the  brain  sui-face  is  divided  into  lobes.  The  general 
arrangement  is  shown  in  Figs.  209  a  and  b.  The  chief  lobes 
are  the  frontal,  the  parietal,  the  occipital,  the  temporal,  the  insular, 
the  limbic,  and  the  olfactory.  On  the  inner  side,  from  before  back- 
wards, we  have  the  marginal,  the  paracentral,  the  pre-cuneus,  the 
cuneus  ;  and  in  close  proximity  to  the  corpus  callosum,  the  cingu- 
him  or  supra-callosal  convolution  above,  and  the  hippocampal  con- 
volution and  the  uncus  below.  The  chief  fissures  separating  these  are 
the  Sylvian  fissure,  the  central  sulcus  or  fissure  of  Rolando,  the  parieto- 
occipital fissure,  the  calcarine  fissure,  the  collateral  fissure,  and  the 
calloso-marginal  fissure.  Each  of  the  main  lobes  mentioned  above 
is  further  subdivided  by  smaller  fissures.  The  extent  of  these  secondary 
fissures  varies  from  l)rain  to  brain,  the  higher  types  of  brain  being  richer 
in  convolutions  than  those  of  the  more  primitive  races. 

The  gradual  evolution  of  the  cerebral  cortex,  and  the  concomitant 
shifting  of  the  chief  afferent  impulses,  arising  in  the  projicient  sense- 
organs  from  the  lower  ganglia  to  the  higher  educatable  cortex,  is  well 
shown  in  the  accompanying  diagrams  from  Monakow  (Fig.  210).  In 
the  lower  fishes  practically  all  the  reactions  to  visual  impressions  are 
carried  out  by  the  optic  lobes.  In  the  higher  types  the  reflexes  through 
these  lobes  become  subordinated,  first  to  the  more  complex  organ  of 
the  optic  thalamus  (where  representatives  from  all  the  afferent  tracts 
of  the  body  assemble),  and  later  to  the  still  more  complex  occipital 
cortex,  when  the  reactions  are  determined  not  only  by  inherited 
nerve-paths  but  also  by  the  various  blocks  and  facilitations  imprinted 
on  the  nerve-paths  by  the  experience  of  the  individual  him.self. 

The  original  cavities  of  the  hemispheres  form  the  lateral  ventricles, 
each  of  which,  in  the  adult  brain,  is  prolonged  into  the  main  divisions 
of  the  hemispheres  as  the  anterior  horn,  the  posterior  horn,  and  the 
inferior  horn.  Each  lateral  ventricle  is  roofed  over  by  the  corpus 
callosum  and  the  adjoining  white  matter  of  the  hemispheres.  On 
opening  the  ventricle  we  see  on  its  floor  the  body  of  the  fornix,  a 
flattened  tract  of  white  matter  with  longitudinal  fibres,  whicii  in  fnmt 
bifurcates  into  two  cylindrical  bundles  which  pass  vertically  down- 
wards in  front  of  the  foramen  of  Monro  into  the  mesial  part  of  the 
subthalamic   tegmentum.     Internal   to  the  fornix  is  a   layer  of   pia 


^74 


PHYSIOLOGY 


Forebrain 


■^':.  Midbrain 

Cerebellum 


Eyer 


B 


Cortex 


Occipital  cortex 


Midbrain  .rh 
Cerebellum 


Pallium 


—  Occipifsl  cortex 


.Cerebellum 


,..  2.0.  Dia.ra.s  fro.  ^^^^  ^^j^ :;::^tJ:t^ 

pallium,  and  the  f'^'lfj-^'^^^'^'f thence  tc,  the  oceipital  cortex, 
inid-brain  to  the  fore-bran,   ar^d  then  ^^^^^    ^^^^ 

K  a  bony  fish.     B,  brain  of  a  lizard.     C,  brain 


STRUCTURAL  ARRANGEMENTS  OF  CEREBRUM       475 

mater,  including  the  choroid  plexus.  On  removing  this  the  third 
ventricle  is  opened,  so  that  in  this  region  the  wall  of  the  cerebral  hemi- 
spheres, like  the  roof  of  the  third  ventricle,  is  limited  to  a  simple  layer 
of  ependyma.  At  the  margin  of  the  choroid  plexus  can  be  seen 
a  part  of  the  superior  surface  of  the  optic  thalamus,  separated,  however, 
from  the  cavity  of  the  ventricle  by  a  layer  of  ependyma.  Outside 
and  in  front  of  the  optic  thalamus  are  the  masses  of  nervous 
material  constituting  the  cor- 
pus striatum.  These  present 
two  nuclei  of  grey  matter, 
known  as  the  nucleus  cau- 
datus  and  the  nucleus  lenticu- 
laris  (Fig.  211).  The  crusta 
of  the  crura  cerebri  as  it 
ascends  to  the  cerebral  hemi- 
spheres passes  behind  between 
the  optic  thalamus  and  the 
corpus  striatum,  and  in  front 
between  the  nucleus  lenticu- 
laris  and  nucleus  caudatus  of 
the  corpus  striatum.  Outside 
the  corpus  striatum  we  find 
another  mass  of  white  fibres, 
known  as  the  external  capsule, 
and  this  is  separated  from  the 
white  matter  of  the  cortex 
cerebri  by  a  thin  layer  of  grey 
matter  known  as  the  claus- 
trum.  In  a  horizontal  section 
through  the  brain,  the  part 
of  the  internal  capsule  which 
pierces  the  corpus  striatum 
forms  an  angle  with  the  pos- 
terior part  separating  the  optic 
thalamus  from  the  lenticular 
nucleus.  The  part  where  the 
two  limbs  come  in  contact  is 
known  as  the  genu  of  the 
internal  capsule. 


Fig.  211.  Horizontal  section  through  the 
optic  thalamus  and  corpus  striatum, 
the  'basal  ganglia.'    (Natural  size.) 

vl,  lateral  ventricle,  its  anterior  eornu  ; 
cc,  corpus  callosum  ;  si,  septum  lucidum  : 
of.  anterior  pillars  of  the  forni.x  ;  v'i.  third 
ventricle ;  tk,  thalamus  opticus ;  st,  stria 
meduUaris  ;  nc,  nuclciis  caudatus,  and 
nl,  nucleus  lenticularis  of  the  corpus  stria- 
tum ;  ic,  internal  capside  ;  </,  its  angle  or 
genu  ;  nc,  tail  of  the  nucleus  caudatus 
appearing  in  the  descending  cornu  of  the 
lateral  ventricle  ;  cl,  dauslruin  ;  /.  island 
of  Reil. 


THE   OLFACTORY   APPARATUS   OF   THE   BRAIN 
In  man  the  olfactory  sense  is  but  feebly  developed,  and  the  parts 
of  the  brain   connected  therewith   are   inconsjiicuous  in  comjiarison 
with  those  engaged  in  the  reception  of  impressions  from  the  other  two 


470 


PHYSIOLOGY 


main  projicieiit  sense-organs,  namely,  sight  and  hearing.  On  this 
account  it  is  not  easy  to  make  out  the  connections  of  the  olfactory  lobe 
proper,  the  rhinence'phalon,  with  the  primitive  part  of  the  cortex,  the 
archipallium,  subserving  the  oKactory  sense  and  probably  the  allied 
sensations  derived  from  the  mouth  cavity.  The  wide  connections  of 
the  olfactory  sense-organs  with  the  different  parts  of  the  brain  in  the 
lower  vertebrate  are  shown  in  the  diagrammatic  figure  of  the  brain  of 
a  reptile  (Fig.  208,  p.  471). 

In  man  it  is  interesting  to  note  that  the  olfactory  nerve  fibres  are 
derived  from  cells  situated  actually  on  the  surface  of  the  body.  These 
are  bilateral,  spindle-shaped  cells,  lying  in  the  olfactory  mucous  mem- 
brane at  the  upper  part  of  the  nasal  cavity.  The  peripheral  process  is 
short  and  passes  towards  the  surface,  while  the  deep  process  passes 
as  a  non-medullated  nerve- fibre  through  the  cribriform  plate  of  the 


Fig.  212.     Schema  of  course  of  olfactory  impulses.     (Ramon  y  Cajal.) 
A,  olfactory  mucous  membrane  ;  B,  olfactory  glomeruli ;    c,  mitral  cells ; 
E,  granule  cells  ;  D,  olfactorj^  tract  ;  l,  centrifiigal  fibres. 

ethmoid  to  sink  into  the  olfactory  bulb.  The  bulb,  in  man,  is  a  greyish 
enlargement  at  the  anterior  end  of  the  olfactory  tract.  In  sections 
stained  by  Golgi's  method  of  impregnation  it  may  be  seen  that  the 
olfactory  fibres  terminate  in  an  arborisation  in  close  connection  with 
a  thick  end  arborisation  derived  from  a  dendrite  of  a  large  nerve-cell, 
known  as  a  mitral  cell.  The  synapses  between  these  two  sets  of  fibres 
are  prominent  objects  in  a  section  through  the  olfactory  bulb  and  form 
the  '  olfactory  glomeruli '  (Fig.  212).  The  axons  of  the  mitral  cells 
pass  back  in  the  olfactory  tracts.  Each  olfactory  tract  divides 
posteriorly  into  two  roots,  the  mesial  root  which  curves  inwards  behind 
Broca's  area  and  passes  into  the  end  of  the  callosal  gyrus,  and  the 
lateral  root  which  runs  backwards  and  over  the  outer  part  of  the 
anterior  perforated  spot.  Its  fibres  pass  into  the  uncinate  extremity 
of  the  hippocampal  gyrus.  The  small  triangular  field  of  grey  matter 
between  the  diverging  roots  of  the  olfactory  tract  is  known  as  the 


STRUCTURAL  ARRANGEMENTS  OF  CEREBROI       477 

olfactory  tubercle.  The  primitive  rhinencephalon  includes  in  the 
adult  human  brain  the  (olfactory  bulb  and  tract,  together  with  the 
anterior  perforated  space,  the  anterior  part  of  the  imcinate  gyrus, 
the  subcallosal  gyrus,  the  septum  lucidum,  and  the  hippocampal 
convolution.  The  two  sides  of  the  rhinencephalon  are  united  by  fibres 
passing  through  the  anterior  commissure.  Other  tracts  subserving 
this  apparatus  include  the  habenula  passing  from  the  fornix  to  the 
ganglion  of  the  habenula,  the  fasciculus  retroflexus  passing  from  this 
to  the  interpeduncular  ganglion,  and  the  corpus  mammillare  which 
is  connected  with  the  column  of  the  fornix  on  the  one  hand  and  through 
the  bundle  of  Vicq  d'Azyr  with  the  thalamus  on  the  other. 

THE  CHIEF  TRACTS   OF  THE  CEREBRAL   HEMISPHERES 

We  may  divide  the  tracts  of  the  upper  brain  or  cerebral  hemispheres 
into  three  classes  : 

I.  Tracts  connecting  the  brain  with  lower  levels  of  the  central 
nervous  system. 

II.  Tracts  connecting  different  parts  of  the  cortex  of  one  hemi- 
sphere and  serving  as  a  means  of  association  between  these  different 
j)arts. 

III.  Tracts  (commissural)  connecting  the  two  cerebral  hemi- 
spheres together. 

I.     THE   PROJECTION  FIBRES 

These  are  the  fibres  which  connect  the  cerebral  cortex  with  the 
different  lower  levels  of  the  central  nervous  system.  They  form  a 
great  part  of  the  fibres  of  the  corona  radiata  and  are  condensed  at  the 
base  of  the  brain  into  the  broad  band  of  fibres  known  as  the  internal 
capsule.  A  few  of  the  fibres  of  the  projection  system  may  gain  the 
cortex  through  the  lenticular  nucleus  and  by  the  external  capsule. 
The  projection  fibres  may  be  divided  into  two  groups  according  as 
they  conduct  impulses  to  or  away  from  the  cerebral  cortex :  the 
afferent  or  corticipital,  and  the  efferent  or  corticifugal. 

A.  AFFERENT  TRACTS  OF  THE  CEREBRUM. 

(1)  The  thalamo-cortical.  From  all  parts  of  the  optic  thalamus 
fibres  arise  as  axons  of  the  cells  of  its  grey  matter  and  streaming  out 
from  its  outer  and  under  surfaces  pass  to  every  part  of  the  cortex. 
Although  there  is  no  division  of  them  into  distinct  groups  as  they  leave 
the  thalamus,  they  are  often  described  as  constituting  a  frontal,  a 
parietal,  an  occipital,  and  a  ventral  stalk.  The  front  fibres  pass 
through  the  anterior  limb  of  the  internal  capsule  to  reach  the  cortex 
of  the  frontal  lobe,  many  of  the  fibres,  however,  terminating  in  the 
caudate  and  lenticular  nuclei.  The  parietal  fibres  issuing  from  the 
lateral  surface  of  the  thalamus  pass  through  the  internal  capsule  to  be 


478 


PHYSIOLOGY 


distributed  chiefly  to  the  parietal  k)be.  The  occipital  fibres  issue  from 
the  outer  part  of  the  pulvinar  and  constitute  the  so-called  '  optic 
radiation,'  passing  outwards'and  backwards  to  be  distributed  to  the 
cortex  of  the  occipital  lobe.  The  ventral  fibres  pass  downwards  and 
outwards  below  the  lenticular  nucleus  and  end  partly  in  the  latter 
nucleus  and  partly  in  the  cortex  of  the  temporal  lobe  and  of  the  insula 
or  island  of  Reil. 


p.  CALLOSUM 


ANT'?  LIMB 
INT- CAPSULE 


LOBt 


Fig.  213.     Schema  of  projection  fibres  of  cortex.     (Cunningham.) 


(2)  The  fillet  system  of  fibres.  This  great  mass  of  ascending 
fibres  has  been  already  described  {cp.  Fig.  198)  as  gathering  up  the 
impulses  from  the  different  sensory  nerves  of  the  cerebro-spinal  system 
and  terminating  in  the  thalamus  and  subthalamic  region.  According  to 
some  observers  a  certain  number  of  its  fibres  pass  through  the  thalamus 
to  reach  the  cortex  without  interruption,  but  this  is  probably  incorrect. 

(3)  The  superior  cerebellar  peduncle.  These  fibres,  from 
the  central  ganglia  of  the  cerebellum,  terminate  for  the  most  part  in 
the  thalamus  and  subthalamic  region.  It  is  possible  that  some  of 
them  may  pass  through  the  hinder  end  of  the  internal  capsule,  without 
interruption  in  the  thalamus,  to  end  in  the  Rolandic  area. 


STRUCTURAL  ARRANGEMENTS  OF  CEREBRl^I       479 

(4)  The  optic  radiation.  These  diver^aiig  fibres  in  the  back  part 
of  the  corona  radiata  are  mixed  up  with  fibres  which  are  partly  cortici- 
fugal.  The  corticipital  fibres  arise  in  the  pulvinar  and  the  external 
geniculate  body  and  end  in  the  occipital  cortex. 

(5)  The  auditory  radiation.  These  fibres  consist  of  the  axons 
of  cells  situated  in  the  internal  geniculate  body.  They  pass  through 
the  posterior  limb  of  the  internal  capsule  under  the  lenticular  nucleus 
to  end  in  the  temporal  lobe. 

B.  THE  EFFERENT  PRO- 
JECTION FIBRES. 

(1)  The  pyramidal  tract. 
This  is  composed  of  fibres  which 
arise  from  the  large  Betz  cells  in 
the  ascending  frontal  convolution, 
the  '  motor  area.'  They  pass 
through  the  corona  radiata  into 
the  internal  capsule,  where  they 
occupy  the  genu  and  the  anterior 
two-thirds  of  the  posterior  limb. 
Hence  they  pass  into  the  crusta, 
where  they  occupy  the  middle 
two- fifths  of  this  structure,  and 
are  continued  as  the  pyramids  of 
the  pons  and  medulla  to  the 
upper  part  of  the  spinal  cord, 
where  most  of  them  decussate 
to  the  other  side  to  form  the 
crossed  pyramidal  tracts.  Some 
of  the  fibres  do  not  cross  at 
the  pyramidal  decussation,  but 
are  continued  down  in  the  same 


Fig.  214.  Diagrammatic  representation 
of  the  internal  capsule,  as  seen  in  hori- 
zontal section.     (Cunningham.) 


position  in  the  anterior  columns  of  the  spinal  cord  of  the  same  side, 
forming  the  direct  or  anterior  pyramidal  tracts.  These  fibres  cross 
for  the  most  part  lower  down  in  the  cord,  so  that  the  direct  pyramidal 
tract  is  not  seen  below  the  cervical  region.  The  pyramidal  tracts  are 
not  found  in  lower  vertebrates,  and  make  their  first  appearance  in  the 
mammalia.  Their  development  corresponds  with  the  gradual  increase 
in  the  direct  interference  of  the  cerebral  cortex  in  the  reactions  of  the 
organism  as  a  whole  and  are  an  index  to  the  gradual  shifting  of 
these  reactions  from  the  inevitable  to  the  educated  reflex.  The  fibres 
of  the  pyramidal  tract  end  at  various  levels  of  the  spinal  cord  and  can 
be  traced  to  the  lower  end  of  the  sacral  region.  According  to  Schiifer 
they  end  in  the  posterior  cornua,  so  that  their  action  is  to  set  going  a 
reaction  which  could  otherwise  be  elicited  bv  stimulation  of  the  afferent 


480 


PHYSIOLOGY 


fibres  enterino;  by  the  posterior  root  at  the  level  of   the  cord  where 
they  end. 

(2)  The  fronto-pontine  fibres.  These  arise  from  cells  in  the 
cortex  of  the  frontal  lobe,  and  pass  down  in  the  anterior  limb  of  the 
internal  capsule  to  gain  the  mesial  part  of  the  crusta  of  the  crus  cerebri. 
The  fibres  end  in  the  grey  matter  of  the  formatio  reticularis  of  the 
pons,  the  nucleus  pontis. 

(3)  The  temporo-pontine  fibres.  These  arise  from  the  two 
upper  temporal  convolutions,  especially  from  that  area  which  is 
associated  with  hearing.  They  pass  inwards  under  the  lenticular 
nucleus  through  the  hinder  limb  of  the  internal  capsule  to  gain  the 

outer  part  of  the  crusta.  In  this  situa- 
tion this  tract  passes  down  into  the  pons, 
where  it  ends  in  the  nucleus  pontis. 

As  part  of  these  projection  fibres  we 
ought  probably  to  reckon  the  fibres  which 
take  origin  or  end  in  the  corpus  striatum. 
The  afferent  fibres  of  this  body  are  de- 
rived chiefly  from  the  thalamus,  forming 
the  thalamo- striate  fibres.  Other  fibres 
arise  in  the  nuclei  of  the  corpus  striatum 
and  pass  down  in  the  dorsal  portion  of 
the  crusta  to  end  for  the  most  part  in 
the  pons,  the  strio-pontine  fibres. 

The  relative  position  of  these  various 
fibres  in  the  internal  capsule  and  in  the 
crusta  is  shown  in  the  accompanying 
diagrams  (Figs.  214  and  215). 

The  fronto-pontine  and  temporo-pon- 
tine fibres,  which  end  in  the  nucleus  pontis, 
come  there  in  relationship  with  the  fibres 
forming  the  middle  peduncles  of  the  cerebellum  and  derived  chiefly 
from  the  lateral  lobes  of  the  cerebellum.  These  fibres  may  therefore 
be  regarded  as  the  efterent  side  of  the  great  cerebro-cerebellar  connec- 
tions of  which  the  afferent  side  is  represented  by  the  fibres — efferent 
so  far  as  concerns  the  cerebellum— which  pass  from  the  cerebellar 
cortex  to  the  dentate  nucleus  and  thence  by  a  fresh  relay  in  the  superior 
cerebellar  peduncles  to  the  red  nucleus,  optic  thalamus,  and  cortexof  the 
opposite  side.  The  development  of  these  fibres,  as  of  the  lateral 
lobes  of  the  cerebellum,  is  largely  proportional  to  the  growth  of  the 
cerebral  hemispheres.  In  cases  where  there  has  been  congenital 
atrophy  of  one  cerebral  hemisphere  the  crusta  of  the  same  side  and 
the  lateral  lobe  of  the  cerebellum  of  the  opposite  side  also  fail  to 
develop. 


Fig.    21.J.       Transverse  sectiuji 
through    mid-brain    to    show 
position  of  fillet  and  pyramid. 
AQ,  anterior   corpus    quadri- 
geminum  ;  dV,  descending  root 
of  fifth  nerve ;  F,  fillet  (I,  lateral, 
and  m,  mesial  fillet) ;  Pyr,  pyra- 
mid ;  Fr,  fibres  from  frontal  lobe 
to  pons  ;  TO,  fibres  from  occipi- 
tal lobe  to  pons ;  Ne,  fibres  from 
nucleus  caudatus  to  pons  ;    111, 
root  of  third  nerve  ;  8,  jSjdvian 
iter  ;   Rn,  red  nucleus. 


STRUCTURAL  ARRANCJEMENTS  OF  CEREBRUxM      481 

II.      ASSOCIATION  FIBRES 

These  fibres  serve  to  unite  different  portions  of  the  cortex  of  the 
same  hemisphere  and  may  be  classified  into  short  and  long  associa- 
tion fibres.  The  short  association  fibres  pass  round  the  bottom 
of  the  sulci  in  U-shaped  loops  connecting  adjacent  convolutions. 
These  fibres  are  some  of  the  latest  to  acquire  a  medullary  sheath  and 
probably  first  become  functional  as  associated  activity  between  the 
various  portions  of  the  cortex  is  gradually  acquired  by  education. 

The  long  association  fibres  may  be  divided  into  five  groups  as 
follows  : 

(a)  The  uncinate,  fasciculus  passes  from  the  orbital  convolutions 
of  the  frontal  lobe  to  the  front  part  of  the  temporal  lobe  ]ound  the 
stem  of  the  Sylvian  fissure  (Fig.  216). 


Fig.  216.     Chief  association  bundles  of  the  cerebral  hemispheres.     (Ctjnningiiam.) 
A.  Outer  aspect  of  hemisphere.     B.  Inner  aspect  of  hemisphere. 


(6)  The  cingulum  is  closely  associated  with  those  parts  of  the  cere- 
bral cortex  known  together  as  the  limbic  lobe.  In  front  it  originates 
in  the  neighbourhood  of  the  anterior  perforated  space,  passes  round 
the  genu  of  the  corpus  callosum,  and  then  is  carried  backwards  over 
the  upper  surface  of  this  body  to  its  hinder  end,  where  it  turns 
round  and  is  distributed  to  the  hippocampal  gyrus  and  to  the  temporal 
lobe. 

(c)  The  longitudinal  superior  fasciculus  lies  in  the  base  of  the 
frontal  and  parietal  lobes,  and  passing  from  before  backwards  connects 
the  frontal,  occipital,  and  temporal  parts  of  the  cerebral  cortex. 

(d)  The  longitudinal  inferior  fasciculus  runs  along  the  whole  length 
of  the  occipital  and  temporal  lobes,  being  situated  behind  on  the  outer 
aspect  of  the  optic  radiation. 

(e)  The  occipito-frontal  fasciculus  lies  on  tho  inner  aspect  of  the 
corona  radiata  in  intimate  relation  to  the  caudate  nucleus,  and  pro- 
jects out  over  the  upper  and  outer  aspect  of  the  lateral  ventricle 
immediately  outside  the  ependyma. 

31 


482 


PHYSIOLOGY 


III.     THE  COMMISSURAL  FIBRES 

These  are  arranged  in  three  groups  : 

(a)  The  corpus  callosum  forms  a  great  mass  of  white  fibres  passing 
transversely  in  both  directions  between  the  two  hemispheres.  Its 
fibres  are  derived  from  every  part  of  the  cerebral  cortex  with  the 
exception  of  the  olfactory  bulb  and  the  hind  and  fore  parts  of  the 
temporal  lobe.  As  the  fibres  cross  the  middle  line  they  become 
gradually  scattered,  so  that  they  tend  to  connect  wholly  dissimilar 
parts  of  the  cortex  of  opposite  hemispheres.  Each  callosal  fibre 
arises  in  one  hemisphere  and  ends  by  fine  arborisations  in  the  opposite 
hemisphere.     It  may  represent  either  the  axon  of  one  of  the  cortical 


Fia.  217.      Schematic  section  through  cerebral  hemispheres,  to  show  chief 
classes  of  nerve  tracts.     (After  Ram(5n  y  Cajal.) 
A,  corpus  callosum  ;  B,  anterior  commissure  ;  c,  pyramidal  tract ;   a,  cell 
giving  off  projection  fibre  ;  b,  cell  giving  off  commissural  fibre  ;  c,  cell  with 
axon  forming  association  fibres. 

cells  or  a  collateral  from  a  fibre  of  association  or  a  collateral  from  a 
projection  fibre  (Fig.  217). 

(6)  The  anterior  commissure  is  situated  in  the  anterior  wall  of  the 
third  ventricle  between  the  two  pillars  of  the  fornix.  It  connects 
together  the  two  olfactory  lobes  and  portions  of  the  opposite  temporal 
lobes.  In  lower  vertebrates  it  is  almost  entirely  olfactory  in  function, 
but  in  man  the  olfactory  fibres  only  form  a  small  proportion  of  the 
total  number  making  up  the  bundle. 

(c)  The  psalterium  or  hippocampal  commissure  is  a  thin  lamina 
formed  of  transverse  fibres  fiUing  up  the  small  triangular  space  on  the 
under  surface  of  the  hinder  part  of  the  corpus  callosum  formed  by 
the  divergence  of  the  posterior  pillars  of  the  fornix.  Like  the  anterior 
commissure,  the  hippocampal  commissure  is  closely  associated  with 
the  sense  of  smell.     Its  fibres  arise  from  the  pyramidal  cells  in  the 


STRUCTUKAL  ARRANGEMENTS  OF  CEREBRUM      483 

cornu  amraonis  or  hippocampus  and  pass  for  the  greater  part  to  the 
cornu  ammonis  of  the  opposite  side. 

MINUTE  STRUCTURE  OF  THE  CEREBRAL  CORTEX 
The  cortex  of  the  cerebral  hemispheres  consists  of  a  layer  of  grey 
matter  covering  a  central  mass  of  white  fibres.  With  the  growth 
in  size  of  the  brain,  which  accompanies  the  development  of  increased 
intelligence  and  powers  of  adaptation,  the  necessary  increase  in 
cortex  is  rendered  possible  by  the  folding  of  the  surface  into  convolu- 
tions and  fissures.  The  chief  of  these  convolutions  have  already 
been  indicated  in  the  sketch  of  the  anatomy  of  the  brain  (Fig.  209). 

On  section  the  grey  matter  is  seen  to  consist  of  many  layers  of 
nerve-cells  embedded  in  neuroglia  and  nerve  fibres,  both  medullat«d 
and  non-medullated.  The  nerve-cells  vary  in  size  and  shape  ;  one 
kind  of  cell  is,  however,  typical  of  this  part  of  the  central  nervous 
system.  This  is  the  pyramidal  cell  (Fig.  218),  a  cone-shaped  or  pear- 
shaped  cell  with  one  large  apical  dendrite  which  runs  towards  the 
surface  and  breaks  up  in  the  most  superficial  layer  into  a  number  of 
branches.  Dendrites  are  also  given  ofE  from  the  sides  and  lower  angles 
of  the  cell.  The  axon,  which  arises  from  the  axon  hillock  in  the  middle 
of  the  base  of  the  cell,  passes  downwards  into  the  white  matter,  giving 
ofi  collaterals  in  its  course.  Some  of  these  axons  pass  by  the  corona 
radiata  into  the  internal  capsule  and  into  the  crura  cerebri,  including 
those  which  form  the  pyramidal  tracts  ;  others,  or  their  collaterals, 
may  pass  into  the  adjacent  regions  of  the  cortex,  or  across  by  the 
corpus  callosum  into  the  opposite  hemisphere. 

Although  varying  in  structure  at  different  parts,  it  is  generally 
possible  to  distinguish  four  or  five  layers  in  the  cortex. 

(1)  The  most  superficial  layer,  known  as  the  outer  fibre  lamina,  or 
molecular  layer,  contains  very  few  cells.  It  is  composed  generally 
of  the  dendrites  of  cells  from  the  deeper  layers.  It  contains  a  few  cells 
which  are  spindle-shaped  and  are  provided  with  several  processes 
running  parallel  to  the  surface.  These  are  sometimes  called  association 
cells.  It  is  probable  that  afferent  fibres,  entering  the  cortex,  pass 
up  towards  the  surface  and  end  for  a  large  part  in  this  molecular  layer. 

(2)  Below  this  is  a  layer  of  pyramidal  cells,  the  outer  cell  la^nina, 
which  is  divided  by  some  observers,  e.g.  Campbell,  into  three,  viz.  : 

(a)  The  small  pyramidal  cells. 

(b)  Medium-sized  p}T:amidal  cells. 

(c)  Internal  layer  of  large  pyramidal  cells. 

(3)  Below  the  pyramidal  layer  we  find  a  stratum  of  small  cells, 
most  of  which  are  stellate  in  form.  This  is  known  as  the  stellate  or 
granule  layer,  or  middle  cell  lamina. 

(4)  Internal  to  the  granule  layer  is  the  itiner  Jibre  lamina.    In  the 


484 


PHYSIOLOGY 


motor  cortex  and  in  certain  other  parts  of  the  brain  this  contains 
large  solitary  cells,  which  in  the  motor  area  receive  the  name  of  the 
cells  of  Betz. 

(5)  Most  internal  of  all,  lying  next  to  the  white  matter,  is  the 


Fig.  218.     Schematic  representation  of  the  neuro-fibrillar  apparatus  of  a 

cortical  pyramidal  cell.     (After  Cajal.) 

a,  axon  ;    dh,  dendrites. 

polymorphous  layer  or  inner  cell  lamina,  composed  of  many  types  of 
cells,  among  which  spindle-shaped  cells  predominate.  Other  cells  are 
also  found  resembling  pyramidal  cells  of  the  more  superficial  layer, 
but  directed  in  the  reverse  direction,  so  that  their  axons  take  a  course 
towards  the  surface.  These  are  the  cells  of  Martinotti.  We  also  find 
Golgi  cells  with  a  freely  branching  axon,  which  terminates  in  the 
adjacent  grey  matter. 


STRTJCTTTRAL  ARRAXaEMEN"TS!  OF  r'EREBRTTM       485 

If   sections  of   the  cortex  be  stained  by  some  method  such  as 
Weigert's,  which  displays  medullated  nerve'fibres,  sheaves  of  radial 


nz 


IT 


Flu.  219.     Diagrammatic  section  of  cerebral  cortex.     (From  Babker  after 
Starr,  Strong,  and  Leamixg.) 
I,  molecular  layer  with  a,  bi-polar  cell ;  II,  layer  of  small  pyramidal  cells; 
III,  layer  of  large  pyramidal  cells  ;  1V^  polymorphous  layer ;  V,  whit<'  matter. 

fibres  may  be  seen  running  from  the  white  centre  towards  the  surface 
and  giving  o£E  a  rich  meshwork  of  fibres  to  the  intervening  portions  of 


486  PHYSIOLOGY 

the  grey  matter.     In  addition  bands  of  tangential  fibres  are  seen 
running  parallel  to  the  surface  in  certain  situations,  viz.  : 

(a)  A  layer  of  very  fine  fibres  just  under  the  surface  of  the  cortex. 
This  layer  is  especially  marked  in  the  hippocampal  convolution  and 
is  but  slightly  developed  in  other  regions  of  the  cortex. 


(1)  Molecular    or  outer 
fibre  lamina. 
0.34  mm. 


(2)  Pyramidal  or   outer 
cell  lamina. 
0.90  mm. 


(3)  Granular     layer    or 
middle  cell  lamina. 
0.22  mm. 


(4)  Inner  fibre  lamina. 
0.22  mm. 


(5)  Polymorphic  or  inner 
cell  lamina. 
0.31  mm. 


a.  Tangential  layer. 


6.  Outer  line    of    Bail- 
larger. 


c.  Inner   line    of    Bail- 
larger. 


Fig.  220.     Motor  leg  area. 

(6)  A  layer  between  the  molecular  layer  and  the  layer  of  pyramidal 
cells,  known  as  the  outer  line  of  Baillarger. 

(c)  Internal  to  the  granule  layer  is  another  zone  of  fibres,  the 
inner  line  of  Baillarger,  giving  its  name  to  the  inner  fibre  lamina. 

(d)  In  the  part  of  the  occipital  cortex,  distinguished  as  the  visuo- 
sensory  area,  which  receives  fibres  of  the  optic  radiations,  a  special 
layer  of  tangential  fibres  is  observed  running  through  the  middle  of  the 
granular  layer  and  dividing  it  into  two  parts.  This  is  known  as  the 
line  of  Gennari  (Fig.  221a). 


STRUCTURAL  ARRANGEMENTS  OF  TERERRUM      487 

A  careful  study  of  the  histology  of  the  different  parts  of  the  cortex 
in  man  enables  us  to  distinguish  certain  types  of  structure  characteristic 
of  various  regions  of  the  grey  matter.  In  attempting  by  such  means 
an  histological  localisation  of  functions  we  have  to  take  into  account  : 

(a)  The  thickness  of  the  cortex. 


(1) 

0-25 


(2) 
0-52 


ro-2\ 


(3). 


0-21(1 


,0-28 


(4) 
0-14 

(5) 
0-28 


Fio.  221a.     Visuo-sensory. 


Fig.  221b. 


Visuo-psychic. 


(1) 
0-27 


(2) 
0-86 


(3) 
0-20 


(4) 
0-22 


(5) 

0-29 


(6)  The  relative  thickness  of  the  various  layers. 

(c)  The  character  of  the  cells  found  in  the  various  layers. 

{d)  The  arrangement  and  degree  of  development  of  the  systems  of 
meduUated  fibres,  both  radial  and  transverse. 

The  possibilities  in  such  a  method  are  at  once  apparent  if,  as  in 
Figs.  220  and  221,  we  compare  the  structure  of  the  cortex  from,  e.g., 
the  pre -central  motor  convolution,  the  visuo -sensory  area  of  the 
occipital  convolution,  and  the  '  visuo-psychic  '  area.  The  finer  differ- 
ences are  not  so  readily  perceptible  without  careful  study  and  measure- 


488  PHYSIOLOGY 

ment  of  the  various  layers  and  the  elements  constituting  them.  By 
this  method  we  can  mark  out  the  cortex  into  areas,  which  agree  closely 
with  the  localisation  of  functions  as  arrived  at  by  experimental  methods 
or  by  a  study  of  the  systems  of  fibres  in  the  brain  or  of  the  functional 
defects  observed  under  pathological  conditions. 

The  localisation  arrived  at  in  this  way  is  represented  in  the  diagrams 
taken  from  Campbell  (Fig.  222).  Thus  in  the  motor  area,  the  precentral 
or  ascending  frontal  convolution,  we  find  below  the  granular  layer  the 
well-marked  pyramidal  cells  or  Betz  cells,  which  are  larger  than  any 
other  element  in  the  cerebrum.  The  layer  of  pyramidal  cells  is  also 
very  thick,  while  the  granular  layer  is  but  slightly  developed.  In  this 
area  the  actual  average  thickness  of  the  different  layers  is  as  follows  : 


Molecular  or  outer  fibre  lamina 


0-34  mm. 


Pyramidal  or  outer  cell  lamina        ....  0-90  mm. 

Granular  or  middle  cell  lamina        ....  0*22  mm. 

Betz  or  inner  fibre  lamina 0-22  mm. 

Polymorphous  layer  or  inner  cell  lamina        .        ,  0-31  mm. 

In  the  visuo-sensory  area  the  granular  layer  is  the  thickest,  and  is 
divided  into  two  layers  by  the  band  of  tangential  fibres  forming  the  line 
of  Gennari.  In  the  association  areas,  both  those,  such  as  the  inter- 
mediate precentral  and  visuo-psychical,  which  are  normally  associated 
with  motor  or  sensory  processes,  as  well  as  the  higher  association 
centres  of  Flechsig,  i.e.  the  frontal  and  parietal  temporal  lobes,  the 
most  niarked  feature  in  the  section  is  the  great  development  of  and 
the  large  number  of  cells  observed  in  the  outer  cell  lamina  or  pyramidal 
cell  layer.  It  will  be  noticed,  too,  that  the  audito-sensory  area  is  but 
small  in  extent  and  lies  almost  entirely  within  the  lijjs  of  the  fissure 
of  Sylvius,  while  the  greater  part  of  the  superior  temporal  convolution, 
which  on  the  left  side  is  associated  with  the  auditory  images  and 
associations  necessary  for  the  comprehension  of  speech,  partakes  of 
the  character  of  an  intermediate  or  psychic  sensory  area. 

The  same  method  may  be  applied  to  a  coniparison  of  the  relative 
development  of  the  cerebral  functions  in  different  types  of  animals. 
A  comparison  of  the  brain  of  the  dog.  ape,  and  man  shows  that  while 
the  absolute  amount  of  brain  substance  devoted  to  the  elementary 
functions  of  movement  and  sensation  remains  practically  the  same 
throughout,  in  man  these  areas  are,  relatively  to  the  whole  brain, 
very  much  diminished  in  size,  the  greater  part  of  the  brain  surface 
being  taken  up  with  the  nervous  material  of  the  type  which  is  con- 
nected with  the  functions  of  association  involved  in  the  higher  pro- 
cesses of  reflection,  intelligence,  and  volition. 

If  we  draw  still  lower  animals  into  the  sphere  of  our  observations 
we  are  enabled  to  form  some  idea  as  to  the  relative  significance  of 


STRUCTURAL  ARRANGEMENTS  OF  rEREBRLTM      489 

^    r.f  f>,P  rortex      Thus  in  an  animal,  such  as  the 
the  various  elements  of  the  cortex      i  ^.^^^^^^^  ^^^  ^^^ 

rabbit,  the  polymorphous  layer  is    ^r^^  ^^^^^^  ,er  range  of 

pyramidal  layer ;  whereas  in  man,  xMth  an  intinitei>  g 

A 


B 


F.„.  m.     H,„„.u  >,n,i„  »ho„i„g  outer  (A)  ™;  .-■■;^^^^^^^^^^^^^^ 
the  cortex.     (Campbell.) 

.action,  .t  is  only  one-third  of  the  thi.k-e.  of  this  laX-    « -;-^ 

roughly  assign  a  function  to  -'''.  f ,  ^,'',  .^  Pfj;  ;,:'    iLssociative 
cortex,  «-e  may  say  that  the  pyram.dal  ce    la>  er ..   u,e.. 
i„  functions.     The  large  pyranndal  cells  of    Bet.  are 


490  PHYSIOLOGY 

granular  layer  is  sensory,  while  the  polymorphous  layer  presides  over 
the  lowest  cortical  functions,  such  as  those  concerned  in  the  getting  of 
food,  the  sexual  instincts,  and  so  on. 

The  description  given  above  applies  to  the  whole  of  the  neopalUum. 
In  the  more  primitive  part  of  the  brain,  the  archipallium,  represented 
by  the  hippocampus,  we  find  only  two  cell  laminae  which  are  homolo- 
gous with  the  middle  (granule)  and  the  inner  polymorphous  cell  layers 
of  the  neopallium. 


SECTION  XVII 

THE  FUNCTIONS  OF  THE  CEREBRAL 
HEMISPHERES 

In  an  animal  possessing  cerebral  hemispheres  it  is  impossible  to 
foretell  with  certainty  what  particular  reaction  may  be  evoked  by 
any  stimulus.  The  animal  which  has  been  deprived  of  its  hemi- 
spheres can,  as  we  have  seen,  be  played  on  at  will,  whereas  the  intact 
animal  is  an  individual  whose  actions — to  judge  by  our  own  experience 
— are  guided  by  intelligence,  and  influenced  by  motives  or  by  feelings 
of  fear,  hunger,  pain,  and  the  like.  In  short,  its  behaviour  is  analogous 
to  that  which  in  man  we  associate  with  conscious  feeling  and  volition. 
This  association  of  the  volitional  manifestations  with  the  cerebral 
hemispheres  has  long  been  assumed,  and  is  borne  out  by  the  exact 
parallelism  existing  between  the  degree  of  intelligence  with  which  an 
animal  is  endowed  and  the  extent  of  development  of  its  cerebral 
hemispheres.  Moreover  in  man  himself  there  is  a  proportionality 
between  the  average  size  of  the  brain,  i.e.  of  the  cerebral  hemispheres, 
and  the  average  intelligence  of  the  race. 

Earlier  attempts  to  analyse  the  factors  entering  into  the  sphere  of 
consciousness  and  to  associate  with  these  factors  localised  parts  of  the 
brain  failed,  largely  on  account  of  a  faulty  psychological  analysis  and 
the  absence  of  any  proper  experimental  groundwork  for  the  conclusions 
put  forward.  Gall,  the  founder  of  phrenology,  recognised  more 
clearly  than  previous  authors  that  the  cerebral  hemispheres  must  be 
regarded  ds  the  material  basis  of  consciousness.  Impressed,  however, 
by  the  fact  that  there  was  no  proportionality  between  the  acuteness 
of  the  senses  and  the  degree  of  development  of  the  cerebral  hemispheres, 
he  considered  that  any  division  of  functions  among  different  parts 
of  the  hemispheres  must  relate  to  highly  complex  psychical  conditions, 
and  therefore  on  very  slender  gi-ounds  allotted  to  parts  of  the  brain 
functions  such  as  those  of  intelligence,  memory,  judgment,  amativeness, 
and  so  on.  These  conclusions  of  Gall  were  overthrown  by  Flourens 
on  both  theoretical  and  experimental  grounds.  In  the  first  place, 
Flourens  pointed  out  that  the  mental  faculty  of  man  cannot  be  divided 
up  into  a  number  of  different  independent  qualities  or  faculties,  such 
as  those  proposed  by  Gall.  In  the  second  place,  he  showed  that  in 
the  pigeon,  although  loss  of  the  whole  cerebral  hemispheres  destroyed 

491 


492 


PHYSIOLOGY 


COR 


intelligence  and  associative  memory  with  the  actions  founded  on  such 
endowments,  removal  of  portions  of  the  brain  caused  simply  a  lowering 
of  these  functions,  and  it  was  a  matter  of  indifference  whether  the 
brain  substance  was  taken  from  the  anterior  or  from  the  posterior 
portions  of  the  hemispheres.  Flourens  therefore  concluded  that  the 
cerebral  hemispheres  acted  as  a  whole  as  the  seat  of  the  will  and  intelli- 
gence. There  is  no  doubt  that  Flourens  was  so  far  perfectly  correct, 
since  all  parts  of  the  brain  must  co-operate  in  determining  the  psychical 

condition  of  any  individual 
A5G  in  any  given  moment.     He 

Scr  was,  however,  as  later  re- 

searches showed,  in  error  in 
thinking  that  no  difference 
could  be  distinguished 
between  the  parts  contri- 
buted by  the  various  con- 
volutions of  the  brain  to 
the  organic  whole  which  is 
called  consciousness. 

As  we  have  seen,  histo- 
logical evidence,   which   in 
the  case  of  the  cerebellum 
displays    a     marked     uni- 
formity   throughout     the 
whole  cortex,  in  the  case  of 
the  cerebrum  reveals  strik- 
ing differences  between  its 
various  areas.    The  demar- 
cation of  the  cerebral  cortex 
into  areas  according  to  the 
histological     structure     of 
their  grey  matter  agrees  with,   and  in  many  cases   supplements,  the 
results  procured  by  an  experimental  inquiry  into  the    functions  of 
the  different  parts. 

That  there  is  a  localisation  of  function  in  the  cortex  so  far  as  con- 
cerns the  movements  of  the  two  sides  of  the  body  was  known  to 
Galen,  who  mentions  the  occurrence  of  paralysis  on  one  side  of  the  body 
as  a  result  of  lesions  in  the  brain  of  the  opposite  side.  In  1861  a 
French  physician,  Broca,  confirming  older  statements  by  Dax  and 
Bouillaud,  pointed  out  that  aphasia,  i.e.  loss  of  power  of  speech,  when 
it  occurred  in  right-handed  people  was  always  associated  with  a  lesion 
of  the  third  frontal  convolution  of  the  left  hemisphere,  which  has  ever 
since  that  time  been  known  as  Broca's  convolution.  Hughlings 
Jackson  in  1864  drew  attention  to  the  connection  of  localised  spasms 


Fig.  223.  Upper  surface  of  dog's  brain,  showing 
results  of  excitation.  (Fritsch  and  Hitzig.) 
A,  neck  muscles ;  +,  movements  of  fore 
limb  ;  **,  movements  of  hind  limb  ;  O,  move- 
ments of  face  ;  ASG,  anterior  sigmoid  gyrus  ; 
PSO,  posterior  sigmoid  gyrus  ;  COR,  coronary 
fissures  ;   Scr,  crucial  sulcus. 


FUNCTION'S  OF  THE  CEREBRAL  HEMISPHERES      493 

(Jacksonian  epilepsy)  with  lesions  of  certain  parts  of  the  central 
convolutions.  On  anatomical  t^ounds  Meynert  considered  that  the 
posterior  portions  of  the  hemispheres  were  probably  more  nearly 
connected  with  sensation,  and  the  anterior  with  the  power  of  move- 
ment ;  but  direct  evidence  of  motor  localisation  was  first  brought  by 
Fritsch  and  Hitzig  in  1870.  These  observers  pointed  out,  in  contradic- 
tion of  the  then  received  idea,  that  the  grey  matter  of  the  cortex  was 
excitable,  and  that  it  was  possible  to  evoke  co-ordinated  movements  of 
the  limbs  on  stimulating  the  front  part  of  the  hemispheres  in  dogs  with 
weak  currents.  The  results  of  their  experiments  are  shown  in  Fig.  223. 


Fig.  224.     Tracings  to  show  latent  periods  of  movements  obtained 
by  stimulating : 

A,  grey  matter  ;  B,  underlying  white  matter  of  cortex.     Time- 
marking  =  fJtTjsec.    (F.  Franck.) 

These  experiments  were  soon  after  repeated  and  confirmed  by  Ferrier, 
who  extended  his  observations  to  the  monkey,  and  more  lately  by 
Horsley,  Schafer,  Beevor,  Sherrington,  and  others  in  the  higher 
apes  and  man.  It  was  formerly  a  subject  of  dispute  whether  the 
movements  resulting  from  stimulation  of  the  cortex  were  due  to  the 
excitation  of  the  grey  matter  or  of  the  underlying  white  matter.  The 
following  facts  show  that  the  seat  of  the  excitation  is  in  the  grey 
matter  : 

(1)  A  smaller  strength  of  current  is  required  to  excite  the  grey 
matter  than  the  underlying  white  matter,  after  removal  of  the  grey 
matter. 

(2)  In  animals  poisoned  by  chloral  the  grey  matter  is  inexcitable, 
though  movements  can  still  be  aroused  on  stimulating  the   white 


494  PHYSIOLOGY 

matter.     A  similar  inexcitability  of  the  grey  matter  can  be  produced 
by  painting  it  with  cocaine. 

(3)  The  latent  period  elapsing  between  the  beginning  of  the  stimu- 
lation and  the  occurrence  of  the  movement  in  the  corresponding 
limb  is  longer  when  the  grey  matter  is  excited  than  when  the  stimulus  is 
applied  to  the  white  matter.  The  results  obtained  by  Francois  Franck 
give  a  latent  period  of  -065  sec.  for  the  grey  matter  and  -045  sec. 
for  the  white  matter  (Fig.  224). 

Whether  the  stimulus  acts  directly  on  the  pyramidal  cells  of  the  cortex,  or 
whether,  as  seems  more  likely,  it  is  the  endings  of  the  afferent  nerves  to  the 
cortex  which  are  really  excited  by  the  stimulus,  we  cannot  at  present  determine. 

When  we  compare  different  animals,  such  as  the  dog,  monkey,  and 
man,  we  find  there  is  a  much  finer  differentiation  of  movements  evoked 
by  stimulation  of  the  cortex  in  the  higher  than  in  the  lower  type. 
Whereas  in  the  dog  the  excitable  areas  shade  into  one  another,  in  the 
higher  ape  and  man  the  areas  are  much  more  circumscribed  and  are 
often  separated  from  adjoining  areas  by  an  inexcitable  zone.  The  locali- 
sation of  motor  functions  in  the  cortex  of  the  chimpanzee  is  indicated 
in  the  accompanying  diagxams  by  Sherrington  (Figs.  225,  226).  It  will 
be  seen  that  the  motor  cortex  is  limited,  on  the  convex  side  of  the  brain, 
to  the  precentral  convolution,  or  ascending  frontal  convolution, 
situated  immediately  in  front  of  the  fissure  of  Rolando.  On  the  inner 
aspect  of  the  hemispheres  only  the  corresponding  part  of  this  convolu- 
tion gives  motor  responses  on  excitation.  We  may  say  broadly  that, 
from  above  downwards,  by  stimulation  of  the  precentral  convolution 
we  get  movements  of  the  leg,  arm,  and  face  ;  though,  as  is  shown  in  the 
diagram,  within  these  larger  areas  smaller  areas  can  be  distinguished 
for  definite  co-ordinated  movements  of  the  different  parts  of  the 
body. 

NATURE  OF  MOVEMENTS  EXCITED.  The  movements  obtained 
by  excitation  of  these  areas  resemble  in  every  respect  the  co-ordinated 
movements  observed  during  the  normal  willed  or  spontaneous  activity 
of  the  animal.  Like  the  movements  evoked  by  stimulation  of  a 
sensory  surface,  they  involve  therefore  the  reciprocal  innervation  of 
antagonistic  muscles.  Never  do  we  find  simultaneous  contractions  of 
antagonists,  even  where  two  opposing  centres  are  excited  simul- 
taneously ;  one  reaction  is  prepotent,  as  is  the  case  with  cutaneous 
excitation,  and  this  reaction  is  attended  and  brought  about  by  ordered 
contraction  of  certain  muscles  accompanied  by  an  ordered  relaxation 
of  their  antagonists.  Thus  the  movement  of  opening  the  jaw,  which 
can  be  excited  from  a  fairly  large  area  of  the  cortex,  involves  a  relaxa- 
tion of  the  normal  tone  of  the  masseter  muscle.  Flexion  of  the  leg 
demands  relaxation  of  the  extensor  muscles.  As  in  the  case  of  the 
spinal  reflexes,  this  relaxation,  or  inhibition,  can  be  abolished  under 


FUNCTIONS  OF  THE  CEREBRAL  HEMISPHERES      495 

the  action  of  strychnine,  or  the  toxin  of  tetanus.     After  administration 
of  either  of  these  it  is  impossible  to  evoke  inhibition  of  any  muscle. 

Fig.  225. 

Anus  &  l/a^/na 

Toes 
Ankle  '•., 


Abdomen 
^ Chest 


Shoulder 
Elbow 
Wrist  ^' 

Finders 
&  thumb 


Ear'   ■'       / 
Eyelid, ■•'Closure 

Nose  °^ j^^  Opening    \ 

of  jaw    Vocal 

cords    Mastication 


Sulcus  centralis 


SuLccaUoso 


Fig.  226. 
Sulc.  Central.      '^"us&  Vkglna. 

Sule.precenu:  mary. 


Fig.  225,  outer  surface  ;  Fig.  226,  inner  surface  of  bruin  of  chimpanzee, 
showing  movements  obtained  by  excitation  of  the  motor  areas. 
(Shekrixgton.) 

Excitation  of  the  cortical  centre  for  the  movements  of  the  jaw  causes 
contraction  of  both  closers  and  openers  of  the  jaw,  i.e.  a  strife  in 
which  the  stronger  masseter  muscles  predominate,  so  that  the  jaw  is 
firmly  closed. 


496  PHYSIOLOGY 

The  part  played  by  muscular  relaxation  in  the  response  to  cortical 
stimulation  is  also  well  seen  in  the  case  of  the  eye  muscles.  Stimula- 
tion of  the  centre  for  eye  movements  on  the  convex  surface  of  the 
frontal  lobes  on  the  right  side  causes  '  conjugate  deviation  '  of  both 
eyes  to  the  left.  This  movement  involves  contraction  of  the  right 
internal  rectus  and  left  external  rectus,  and  a  simultaneous  inhibition 
of  the  tone  of  the  right  external  rectus  and  left  internal  rectus.  If  all 
the  muscles  of  the  right  eye  be  divided  except  the  external  rectus,  this 
eye  looks  permanently  towards  the  right  side,  i.e.  a  right  external 
strabismus  or  squint  is  produced.  On  now  exciting  the  right  cortex 
both  eyes  move  to  the  left,  although  the  right  internal  rectus  is  divided. 
The  movement  of  the  right  eye  stops  at  the  middle  Hue,  and  is  brought 
about  simply  by  a  relaxation  of  the  tone  of  the  right  external  rectus 
muscle  (Sherrington). 

This  movement  of  both  eyes  on  stimulation  of  one  side  of  the  brain 
shows  that  the  function  of  each  hemisphere  is  not  entirely  unilateral 
with  regard  to  the  muscles  of  the  body.  As  a  rule  the  response  to 
excitation  of  the  motor  area  for  limbs  is  strictly  unilateral.  In  the 
case  of  those  movements,  however,  which  are  normally  carried  out  by 
co-operation  of  the  muscles  of  the  two  sides,  such  as  the  movements 
of  the  trunk,  neck,  and  eyes,  stimulation  of  the  motor  area  in  one 
hemisphere  evokes  a  movement  involving  the  muscles  of  both  sides 
of  the  body,  i.e.  the  cortical  representation  is  one  of  movement  rather 
than  one  of  muscles.  Where  an  action  is  carried  out  by  similar  con- 
tractions of  corresponding  muscles  on  the  two  sides,  the  movement 
itself  is  bilaterally  represented  in  the  cortex.  Types  of  such  reactions 
are  found  in  closure  of  the  mouth,  contraction  of  the  abdominal 
muscles,  erection  or  flexion  of  the  trunk.  It  seems  that  under  such 
circumstances  there  is  a  free  communication  between  the  lower  motor 
centres  of  the  two  sides,  since  the  bilaterality  of  the  response  is  not 
altered  by  extirpation  of  the  cortex  of  the  opposite  hemispheres  to 
that  which  is  being  stimulated. 

CORTICAL  EPILEPSY.  When  electrical  excitation,  of  any  strength 
over  the  minimum  effective  stimvdation,  is  applied  to  the  motor  area 
of  the  cortex,  the  movements  evoked  tend  to  persist  for  a  short  time 
beyond  the  duration  of  the  stimulus.  On  still  further  increasing  the 
strength  of  the  current,  the  contraction  spreads  to  adjoinmg  muscles, 
and  finally  may  affect  all  parts  of  the  body,  giving  rise  to  the  pheno- 
menon known  as  an  epileptic  convulsion.  The  same  effect  may  often 
be  caused  by  weak  stimuli,  if  the  irritability  of  the  cortex  be  raised  in 
consequence  of  repeated  previous  stimulation.  A  typical  fit  consists 
of  two  parts.  The  first  efEect  of  the  stimulation  is  a  strong  tonic 
contraction  ;  this  outlasts  the  stimulus  for  some  time,  and  then 
gives  way  to  a    series  of    clonic   contractions,  repeated  at  first  at 


FUNCTIONS  OF  THE  CEREBRAL  HEMISPHERES      497 

intervals  of  from  six  to  ten  per  second,  but  gradually  getting  slower 
as  the  fit  dies  away.  The  tracing  of  such  a  contraction  is  given  in 
Fig.  227. 

The  main  phenomena  of  a  fit,  due  to  irritation  of  any  portion  of  the 
motor  area,  were  described  by  Hughlings  Jackson  in  1864,  even 
before  the  experimental  proof  of  cortical  localisation  had  been  brought 
forward  by  Fritsch  and  Hitzig.  A  similar  condition  may  occur  in 
the  human  subject  as  a  result  of  irritative  lesions  of  this  part  of  the 
cortex,  such  as  that  due  to  the  presence  of  a  tumour  oi-  a  spicule  of 
bone  pressing  on  the  brain.  Jackson  showed  that  in  this  condition 
the  convulsive  movements  follow  a  certain  order  or  '  march.'  Thus 
if  the  thumb  area  be  the  seat  of  stimulation,  the  fit  begins  bv  a  contrac- 


FiG.  227.  Tracing  of  muscular  contractions  during  an  epileptic  convulsion 
aroused  by  strong  stimulation  of  the  motor  area.  (Horsley  and 
Sc'hafer). 

tion  of  the  thumb  muscles,  then  spreads  to  the  muscles  of  the  hand, 
fore-arm  and  shoulder  muscles  of  the  same  side,  and  then  to  the  face, 
trunk,  and  leg.  If  it  begins  in  the  toes  the  order  would  be  up  the  leg  and 
down  the  arm.  The  same  '  march  '  is  observed  in  artificial  stimulation  of 
the  motor  area.  If  the  convulsions  are  very  strong  they  spread  to  the 
leg  of  the  opposite  side  and  then  to  the  whole  body.  The  spread  to 
the  other  side  of  the  body  is  not  prevented  by  division  of  the  corpus 
callosum,  nor  by  isolating  the  centres  from  one  another,  so  that  the 
sequence  seems  to  be  maintained  through  the  mediation  of  the  sub- 
cortical centres.  Complete  excision  of  the  cortical  centre  for  any 
given  movement  excludes  this  movement  from  participation  in  the 
fit.  In  man  this  type  of  epilepsy  is,  in  the  milder  easels  at  any  rate, 
generally  unattended  with  loss  of  consciousness.  In  animals  epileptic 
convulsions  can  be  excited  by  stimulation  of  any  portion  of  the  cortex, 
though  it  is  obtained  by  a  weaker  stimulus  applied  to  the  motor  cortex 
than  from  any  other  part.  Jacksonian  epilepsy  is  often  preceded  bv  a 
sensation  of  numbness  or  tingling,  the  '  aura,'  in  the  part  in  which 
such  convulsions  begin.  In  ordinary  idiopathic  epilepsy  tactile  or 
visual  sensory  aursr  may  precede  the  attack  ;  but  in  this  case  lo.ss  of 
consciousness  is  alwavs  a  prominent  svmptom.  even  in  the  milder  form 
of   the   disease.     Universal   epileptic   convulsions   can    be   excited   in 

32 


498  PHYSIOLOGY 

animals  by  the  injection  of  absinthe  into  a  vein.  During  the  convul- 
sion there  is  a  rise  of  blood  pressuie  and  a  quickening  of  the  pulse  ;  the 
respiration  is  very  often  stopped  during  the  tonic  part  of  the  spasm,  so 
that  the  patient  becomes  livid.  The  universal  condition  of  excitation 
affects  also  the  centres  from  which  the  secretory  nerves  originate,  so 
that  there  is  an  excessive  flow  of  saliva,  which,  in  the  idiopathic  case, 
is  responsible  for  the  characteristic  frothing  at  the  mouth. 

EFFECTS  OF  ABLATION  OF  THE  MOTOR  CENTRES 
We  have  seen  that  a  dog  may  preserve  complete  power  of  move- 
ment after  a  total  ablation  of  both  cerebral  hemispheres.  We  should 
not  expect  therefore  to  find  any  lasting  paralysis  as  a  result  of  extirpa- 
tion of  portions  of  the  brain,  such  as  the  motor  centres.  Ablation  of 
the  motor  areas  in  these  animals,  during  the  first  few  weeks  after  the 
operation,  gives  rise  to  considerable  disorders  of  movement,  the 
muscles  on  the  side  of  the  body  opposite  to  the  lesion  being  markedly 
weaker  than  those  on  the  same  side.  These  symptoms,  however, 
gradually  pass  off,  so  that  after  a  time  not  only  are  both  limbs  em- 
ployed in  the  ordinary  automatic  movements  of  progression,  but  the 
animal  can  be  taught  new  movements  in  the  limb,  the  cortical  centre 
for  which  has  been  excised.  We  must  conclude  therefore  that  in  the 
dog  all  the  movements,  including  those  v/hich  are  voluntary  and 
conscious,  can  be  cariied  out  ii\  the  absence  of  the  motor  centres, 
although  destruction  of  these  centres  may  impair  the  accuracy  with 
which  some  of  the  finer  movements  are  regulated. 

In  the  monkey  (Macacus)  the  effect  of  ablation  is  more  marked, 
corresponding  to  the  greater  degree  of  localisation  in  these  animals.  If 
the  whole  of  the  motor  area  on  the  external  surface  of  the  brain  be 
excised,  e.g.  on  the  right  side,  there  will  be  almost  complete  paralysis 
of  the  left  arm  and  the  left  side  of  the  face,  and  weakness  of  the  muscles 
of  the  left  leg.  The  animal  will  continue  to  use  the  leg  in  walking  and 
in  climbing.  If  the  lesion  extends  to  the  medial  side  of  the  hemi- 
sphere paralysis  of  the  leg  is  more  marked,  and  the  muscles  of  the  left 
side  of  the  trunk  are  also  affected.  Many  of  these  symptoms  disap- 
pear in  the  course  of  time.  In  a  monkey  in  which  Goltz  had  destroyed 
the  greater  part  of  the  left  side  of  the  cerebral  hemispheres  it  was 
found  that  the  right  arm  and  hand  could  be  still  employed  alone  for 
such  purposes  as  taking  food,  although  the  movements  were  much 
more  awkward  than  those  of  the  left  hand. 

Still  less  complete  is  the  recovery  from  lesions  of  the  motor  area 
in  man.  We  possess  now  a  considerable  number  of  typical  histories 
of  cases  in  which  part  of  the  motor  cortex  has  been  destroyed  by 
disease  or  by  operation,  and  the  seat  of  the  lesion  verified  by  post- 
mortem examination.     In  all  these  cases  there  has  been  a  loss  of 


FUNCTIONS  OF  THE  CEREBRAL  HEMISPHERES      499 

voluntary  movement  corresponding  in  distribution  to  the  seat  of  the 
lesion  and  proportionate  in  its  severity  to  the  extent  of  the  lesion. 
On  the  other  hand,  equally  extensive  lesions  outside  the  ascending 
frontal  convolution  have  been  shown  to  have  no  effect  on  volun- 
tary movements.  The  loss  of  movement  is  chiefly  confined  to  those 
which  we  regard  as  volitional.  Although,  for  instance,  the  arm  may 
be  paralysed,  it  can  be  still  raised  in  association  with  a  movement 
involving  the  other  arm.  A  certain  degree  of  recovery  from  the 
immediate  effects  of  the  lesion  may  be  observed,  but  the  recovery  is 
never  complete. 

The  difference  in  the  reaction  of  various  animals  to  lesions  of  the 
motor  cortex  is  connected  with  the  gradual  shifting  of  functions 
from  the  sphere  of  fatal  necessary  reactions  to  the  sphere  of  educat- 
able  adaptations  {i.e.  from  the  lower  centres  to  the  cerebral  cortex), 
which  is  a  characteristic  of  the  evolution  of  the  higher  type  of  nervous 
system,  and  is  a  concomitant  of  the  increased  adaptability  which 
distinguishes  man  from  all  the  lower  animals.  In  the  animal  without 
hemispheres  the  motor  mechanisms  for  all  the  movements  of  the 
body  are  present  and  can  be  set  into  action  from  any  point  on  the 
sensory  surface  of  the  body.  The  first  effect  of  adding  the  cerebral 
hemispheres  to  this  mechanism  is  to  increase  the  range  of  reactions, 
to  modify  them  or  to  inhibit  them,  by  diverting  the  stream  of  nervous 
impulses  into  channels  which  have  to  a  large  extent  been  laid  down 
in  the  cortex  by  the  past  experience  of  the  individual.  In  the  frog 
and  bird  we  notice  an  automaticity  and  a  '  conscious  '  adaptation  of 
movements  to  purpose,  although  the  hemispheres  have  no  direct  con- 
nection with  the  motor  centres  of  tlie  cord,  and  present  no  areas 
which  we  can  designate  as  motor.  In  the  dog.  although  a  portion  of 
the  brain  is  in  direct  connection  with  the  spinal  motor  centres,  and 
can  therefore  initiate  movements  without  making  use  of  the  mid- 
brain motor  machinery,  these  movements  play  only  a  small  part 
in  the  motor  life  of  the  animal,  and  the  removal  of  the  corresponding 
centres  takes  away  but  little  of  the  conscious  functions  of  the  animal. 
In  man  the  enormous  power  of  acquisition  of  new  movements  is 
rendered  possible  by  the  shifting  of  one  motor  function  after  another 
to  the  sphere  of  influence  of  the  cerebral  hemispheres.  Almost  every 
act  of  life  in  man  has  become  one  involving  co-operation  of  the  cerebral 
cortex.  For  many  years  after  birth  man  is  helpless  and  far  inferior, 
as  a  reactive  organism,  to  animals  much  lower  in  the  scale.  Even 
the  lower  motor  functions,  such  as  those  of  locomotion  or  defence, 
have  to  be  painfully  learnt,  and  this  learning  implies  the  laving 
down  of  paths  (Bahnung)  in  the  cortex.  On  this  account  the  sub- 
cerebral  centres  in  man  are  no  longer  complete.  Acting  in  every 
instance  of  life  as  a  subordinate  or  adjunct  to  the  cerebral  hemispheres, 


500  PHYSIOLOGY 

they  are  unable  to  carry  out  even  the  simpler  motor  reactions  of  the 
body  after  removal  of  those  portions  of  the  hemispheres  especially 
engaged  in  the  control  of  voluntary  movement.  The  motor 
defect  therefore  which  is  brought  about  in  man,  as  a  result  of 
destruction  of  one  or  more  of  the  motor  centres,  is  to  a  large  extent 
permanent. 

If  the  lesion  in  man  be  strictly  limited  to  the  motor  areas  in  the 
ascending  frontal  convolution,  it  is  impossible  to  detect  any  loss  of 
sensation  in  the  affected  parts  of  the  body.  On  the  other  hand,  some 
loss  of  sensation  is  often  found  where  the  paralysis  is  widespread  and 
occasioned  by  extensive  lesion  in  the  neighbourhood  of  the  Rolandic 
area.  Moreover,  even  in  localised  lesions  in  man,  an  epileptic  fit  may 
be  preceded  by  a  sensory  aura  in  the  part  which  is  the  starting-point 
of  the  convulsive  movements.  Much  discussion  has  taken  place  as 
to  the  exact  significance  to  be  assigned  to  these  slight  sensory  pheno- 
mena. By  some  observers,  e.g.  Munk,  it  has  been  thought  that  the 
motor  centres  were  the  end-stations  of  the  fibres  subserving  nuiscular 
sensations,  and  that  the  movements  resulting  from  their  stimulation 
w^ere  due  to  the  revival  of  such  sensations.  Bastian  insisted  on  the 
important  part  played  in  voluntary  actions  by  afferent  impressions,  and 
these  centres  have  sometimes  been  spoken  of  as  '  kinfesthetic  '  or  sensori- 
motor. The  discussion  has,  however,  now  resolved  itself  practically 
into  one  of  terms.  There  is  no  doubt  that,  when  the  lesion  is  strictly 
localised  in  the  motor  area,  paralysis  may  be  present  without  any 
loss  of  sensation  whatsoever.  The  paralysis  therefore  cannot  be 
classed  with  the  sensori-motor  paralysis  distinguished  earlier  as  the 
result  of  division  of  sensory  roots.  On  the  other  hand,  when  we  say 
that  this  part  of  the  brain  represents  a  '  centre  for  voluntary  move- 
ments,' we  do  not  mean  that  the  volitional  motor  im])ulses  arise  de 
710V0  from  the  pyramidal  cells  in  its  gTey  matter.  Every  neuron  in  the 
nervous  system  is  part  of  an  arc,  and  it  is  generally  difficult  to  label  any 
given  neuron  as  definitely  sensory  or  motor.  In  a  reaction  involving 
a,  chain  of  neurons  we  can  assign  the  name  of  motor  to  that 
neuron  which  sends  its  axon  to  the  muscle,  and  of  setisorij  or  afferent 
to  that  neuron  which  receives  the  impulses  at  the  periphery  of  the 
body.  Where  in  the  chain  we  are  to  draw  the  dividing  line  and  to 
say  these  neurons  are  sensory  and  those  motor,  it  is  difficult  to  decide. 
The  motor  areas  in  the  cortex  give  origin  to  the  long  fibres  of  the  pyra- 
midal tract,  which  passes  right  through  the  central  nervous  system 
to  the  segmental  centres  of  the  cord.  We  know  that  the  integxity  of 
these  tracts  is  essential  for  the  carrying  out  of  voluntary  movement. 
It  is  therefore  convenient  to  speak  of  them  as  motor  or  efferent  tracts, 
and  their  origin  as  motor  centres  ;  although  these  tracts  have  the 
8  une  relation  to  the  motor-cells  of  the  spinal  segment  as  have  the 


FUNCTIONS  OF  THE  CEREBRAL  HEMISPHERES     501 

uliereiit-fibies  from  tlic  postorior  roots  1  a- which  similar  movements 
may  be  evoked. 

On  the  other  hand,  the  activity  ol;  the  pyramidal  cells  ot  the  cortex, 
like  those  of  the  motor-cells  of  the  spinal  coid,  is  determined  by  the 
arrival  at  them  of  afferent  impressions.  In  the  absence  of  these 
afferent  impressions  no  spontaneous  discharge  of  motor  impulses 
takes  place.  Thus  in  the  spinal  frog  we  have  seen  that  complete 
inactivity  is  brought  about  by  section  of  all  the  posterior  roots.  In 
the  same  way  paralysis  of  the  arm  is  induced  by  section  of  all  its 
posterior  roots,  although  it  can  be  shown  that  the  motor  cortex  is  still 
excitable,  and  that  the  application  of  an  induced  current  to  the 
motor  centres  of  the  arm  evokes  a  movement  as  easily  as  in  the  normal 
animal.  The  motor-cells  in  the  cortical  motor  centres  are  normally 
played  upon  and  aroused  by  impressions  arriving  at  them  from  all 
other  parts  of  the  brain  and  nervous  system,  and  determined  originally 
by  impressions  falling  on  the  surface  of  the  body. 

THE  LOCALISATION  OF  SENSORY  FUNCTIONS  IN  THE  CORTEX 

It  was  pointed  out  by  Ferrier  that  movements  might  be  obtained 
on  electrical  excitation  of  regions  of  the  cortex  cerebri  other  than 
those  we  have  described  as  motor.  Thus  excitation  of  the  superior 
temporal  convolution  on  the  right  side  causes  the  animal  to 
turn  its  head  and  eyes  to  the  left  and  to  prick  up  its  ears.  In  the 
same  way  stimulation  of  tlie  right  occipital  lobe  causes  movement 
of  both  eyes  and  head  to  the  left  side.  These  portions  of  the  brain 
cannot  be  regarded  as  having  a  direct  relationship  to  the  motor 
mechanisms  involved  in  the  above  movements,  since  their  ablation 
leads  to  no  defect  of  movement,  but  does,  in  many  cases,  lead  to 
defect  of  sensation.  Thus  excision  of  the  whole  of  the  occipital  lobe 
in  the  monkey,  though  leaving  the  eye  movements  intact,  causes  a 
loss  ot  power  to  discern  objects  lying  to  the  left  of  the  middle  line. 
The  obvious  explanation  therefore  of  the  movements,  obtained  on 
excitation  of  this  portion  of  the  cortex,  is  that  they  are  due  to  the 
revival  or  arousing  of  sensory  impressions,  that  these  portions  of  the 
cortex  represent  the  cortical  receiving  stations  for  the  impulses  from 
definite  sense-organs,  and  that  the  movements  obtained  are  simply 
those  which  are  normally  associated  with  a  corresponding  sensory 
excitation. 

This  conclusion  is  borne  out  by  the  fact  that  it  requires  a  greater 
strength  of  stimulus  to  excite  movement  on  stimulation  of  the  sensory 
areas  than  is  necessary  if  the  stimulus  be  applied  to  the  Rolandic 
area.  Moreover  Schiifer  has  shown  that  the  latent  period  which 
intervenes  between  the  stimulus  and  the  resulting  movement  is 
considerably  longer  when  the  stimulus  is  applied  to  the  sensory  centre 


502 


PHYSIOLOGY 


than  when  it  is  applied  to  the  motor  centre,  suggestuig  that  more 
neurons  are  interpolated  between  the  point  of  stimulus  and  the 
discharging  motor  neuron  in  the  first  case  than  in  the  latter.  Thus 
in  one  experiment  the  latent  period  between  the  stimulus  and  the 
resulting  movement  of  the  eyes  amounted  to  0-2  sec.  when  the 
frontal  lobes  were  stimulated  and  04  sec.  when  the  occipital 
lobes  were  stimulated.  Finally  the  anatomical  investigation  of  the 
course  of  the  fibres  in  the  white  matter  of  the  cerebral  hemispheres 
points  to  a  concentration  of  sensory  fibres  from  different  sense-organs 


'  Tactile '  area 


Visual 
urea 


Auditory  area 


Fig.  228.  Outer  side  of  right  cerebral  hemisphere,  according  to  Flechsig. 
Tile  dotted  surface  indicates  the  regions  where  the  majority  of  the 
afferent  (sensory)  fibres  end. 


\ 


towards  certain  regions  of  the  cortex.  The  diagrams  (Figs.  228 
and  229)  show  those  portions  of  the  brain  to  which  the  endings  of  the 
sensory  tracts  of  the  central  nervous  system  are  directed. 

From  the  purely  anatomical  standpoint  we  may  designate  as 
'  sensory  areas  '  of  the  cortex  : 

(1)  An  area  including  both  central  convolutions,  i.e.  the  ascending 
frontal  and  the  ascending  parietal,  and  spreading  forward  into  the 
frontal  lobes. 

(2)  An  area  occupying  the  hinder  portion  of  the  occipital  lobe 
and  the  greater  part  of  its  inner  surface. 

(3)  An  area  occup3nng  the  superior  temporal  convolution  and 
extending  well  into  the  fissure  of  Sylvius. 

(4)  An  area  on  the  inner  side  of  the  hemisphere,  occupying  the 
hippocampal  Kyrus  and  the  margin  of  the  gyrus  fornicatus  close  to 
the  corpus  callosum. 


FUNCTIONS  OF  THE  CEREBRAL  HEMLSPHERE8     503 

Let  us  see  how  far  experimental  evidence  bears  out  this  localisa- 
tion. 

(a)  TACTILE  AND  MOTOR  SENSIBILITY.  A  lesion  hnuted  to 
the  ascending  frontal  convolution  may  produce  paralysis  of 
definite  movements  or  groups  of  muscles  without  any  detectable 
interference  with  sensation.  When,  however,  in  man  a  wide- 
spread injury,  involving  both  the  Rolandic  area  and  the  adjacent 
portions  of  the  brain,  occurs  as  the  result  of  some  morbid  condition, 
such  as  blockage  of  the  middle  cerebral  artery,  the  resulting  heyni- 
■pleyia  is  almost  always  associated  with  a  gi-eater  or  lesser  degree  of 
hemiancBsihesia.     We  are  therefore  justified  in   locating  tactile  and 


'  Tactile '  area 


Olfactory  area  • 

Fio.  229.     Inner  surface  of  the  same  hemisphere.     (Flechsig.) 

muscular  sensibility  somewhere  in  the  region  of  the  central  convolu- 
tions, and  it  is  probable  that  while  it  may  include  the  motor  area 
its  chief  representation  is  to  be  found  in  the  post-central  gyrus,  i.e. 
the  ascending  parietal  convolution. 

The  sensory  au£a_which  precedes  an  attack  of  Jacksonian  epilepsy 
points  to  the  motor  area  itself  having  some  degree  of  sensory  functions, 
and  it  has  been  observed  that  faradisation  of  the  central  convolution 
in  man  may  produce  tingling  sensations  in  the  part  of  the  body  which 
is  the  seat  of  the  muscular  contractions  induced  by  stimulation. 
No  pain  is,  however,  felt  as  a  result  of  the  stimulation.  The  impulses 
which  subserve  cutaneous  and  muscular  sensibility  travel  up  to  the 
brain  in  the  mesial  fillet.  This  tract  comes  to  an  end  in  the  ventro- 
lateral portion  of  the  thalamus  and  the  subthalamic  region.  The 
new  relays  of  fibres,  which  carry  on  impulses  to  the  cortex,  arise  in 
the  thalamus  and  pass  through  the  hinder  limb  of  the  internal  capsule 


504 


PHYSIOLOGY 


LEFT     RETINA 


RIGHT    RETINA 


to  be  distributed  to  the  central  convokition.s.  Tlieir  area  of  distribution 
is,  however,  much  wider  than  the  area  of  origin  of  che  pyramidal  fibres. 
We  may  therefore  conclude  that  tactile  and  muscular  sensibility  are 
chiefly  subserved  by  the  central  convolutions,  including  the  motor 
area,  but  are  especially  dependent  on  the  integrity  of  the  post-central 
g\TUS.  Flechsig  has  shown  that  fibres  from  the  thalamus,  which  may 
probably  be  regarded  as  continuations  of  the  fillet  system,  are  also 

distributed  to  other  portions 
of  the  cortex,  i.e.  the  temporal, 
the  frontal,  and  the  occipital 
lobes.  It  is  therefore  not 
surprising  that  the  hemi- 
ansesthesia  produced  by  lesions 
in  the  central  convolutions  is 
rarely  or  never  complete. 

VISUAL  IMPRESSIONS 
Each  optic  tract,  carrying 
impulses  arising  as  a  result  of 
events  occurring  in  the  oppo- 
site field  of  vision,  ends  in  the 
pulvinar  of  the  optic  thalamus, 
the  external  geniculate  body, 
and  the  superior  corpora  quad- 
rigemina.     The  last  named  is 
apparently  not  concerned  in 
vision,  but  represents  a  centre 
for  the  co-ordination  of  visual 
impressions  with   those   from 
other  regions  of  the  body  in 
nifluencing  bodily  movements. 
From  the  pulvinar  and  external 
geniculate  body  arises  a  sheaf  of  fibres,  which  pass  through  the  extreme 
hinder  end  of  the  posterior  limb  of  the  internal  capsule  and  diverge 
in  the  centrum,  ovale  to  be  distributed  to  the  occipital  lobes,  being  here 
known  as  the  optic  radiations.  The  anatomical  connection  of  the  occipital 
lobes  with  vision  is  confirmed  by  evidence  derived  from  experiment. 
Movements  of  the  eyes  result  from  stimulation  of  almost  any  part  of  this 
lobe.   If  the  upper  surface  of  the  right  occipital  lobe  be  stimulated,  both 
eves  move  downwards  and  towards  the  left.    Excitation  of  the  posterior 
part  causes  movement  of  the  eyes  up  and  to  the  left ;   while  between 
these  two  parts  there  is  an  intermediate  zone,  most  marked  on  the 
mesial  surface,  stimulation  of  which  evokes  a  purely  lateral  deviation 
of  the  eves  to  the  left.     It  is  therefore  concluded  not  only  that  there 


Fig.  230.  Diagram  showing  tlie  probable 
relations  between  the  parts  of  the  retinaj 
and  the  visual  area  of  the  cortex.  (Schafer. 


FUNCTIONS  OF  THE  CEREBRAL  HEMISPHERES     505 

18  representation  of  visual  impressions  in  the;  occijiital  lobes,  but  that 
there  is  a  certain  amount  of  localisation  within  the  visual  area  itself, 
as  is  represented  in  the  diatrram  (F'ijz.  2."}0). 

These  conclusions  are  fully  boiiie  out 'by  the  results  of  ablation. 
While  extirpation  of  the  whole  occipital  lobe  on  one  side  in  animals 
causes  crossed  hemianopia,  i.e.  has  the  same  effect  as  division  of 
the  corresponding  optic  tract,  extirpation  of  these  lobes  on  both 
sides  causes  complete  blindness.  It  seems  that  the  fovea  centralis 
— the  region   of  distinct  vision — is   bilaterally  represented,   so  that 


Fio.  231.  Perimeter  charts  from  right  and  left  eye,  showing  the  limitation  of  the 
field  of  vision  (right  hemianopia)  produced  by  a  lesion  of  the  left  occipital  cortex. 
(Bechterew.) 

central  vision  is  usually  retained  in  both  eyes  after  destruction  of  one 
occipital  lobe  (Fig.  231). 

The  area  connected  with  vision  seems  to  be  smaller  in  man  than 
in  the  ape,  and  in  the  ape  than  in  the  dog.  Thus  in  man  complete 
blindness  has  been  observed  as  the  result  of  localised  bilateral  lesions 
of  the  internal  surfaces  of  the  occipital  lobes,  and  we  find  the  same 
relative  limitation  of  area  as  we  proceed  from  lower  to  higher  forms 
in  the  ease  of  the  other  sensory  areas  of  the  cortex. 

THE  AUDITORY  AREA 
Anatomical  study  indicates  a  connection  of  auditory  sensations 
with  the  superior  temporal  lobe.  The  impulses,  started  by  the  arrival 
of  sound  waves  at  the  ear,  travel  by  the  cochlear  nerve  to  the  medulla. 
From  the  two  auditory  nuclei  a  well-marked  set  of  fibres  passes 
across  to  the  opposite  side  in  the  corpus  trapezoides.  then  turns  up 
into  the  tegmentum  of  the  opposite  side  to  form  the  tract  known 


506  PHYSIOLOGY 

as  the  lateral  fillet.  The  fibres  of  this  tract  end  partly  in  the  inferior 
corpora  quadrigemina,  partly  'n  the  internal  geniculate  body.  From 
the  latter;  fibres  pass  into  the  internal  capsule,  and  thence  as  '  auditory- 
radiations  '  directly  to  the  superior  temporal  lobe. 

In  the  monkey  stimulation  of  the  upper  two-thirds  of  this  lobe 
of  the  brain  causes  pricking  of  the  opposite  ear,  dilatation  of  the 
pupils,  and  rotation  of  the  head  and  eyes  to  the  opposite  side.  It 
was  stated  by  Ferrier  that  ablation  of  the  superior  temporal  con- 
volution causes  deafness,  but  Schafer  found  that,  even  after  extir- 
pation of  the  superior  temporal  convolutions  of  both  sides,  monkeys 
showed  signs  of  hearing  quite  distinctly,  and  of  understanding  the 
nature  of  the  sounds  heard.  One  must  conclude  therefore  that  the 
function  of  auditory  perception  is  not  entirely  confined  to  the  temporal 
lobe,  though  its  focal  point  may  be  located  in  the  superior  temporal 
convolution,  especially  in  that  part  which  is  seated  within  the  fissure 
of  Sylvius.  This  conclusion  is  strengthened  by  the  results  of  clinical 
evidence  in  man,  in  whom  cerebral  lesions,  which  have  produced 
disturbances  of  auditory  perception,  are  found  almost  invariably 
to  be  closely  associated  with  the  superior  temporal  convolution. 

SMELL  AND  TASTE 
The  course  of  the  fibres  from  the  olfactory  lobe  may  be  used 
to  throw  light  upon  the  localisation  of  olfactory  sensation  in  the 
cerebral  cortex.  There  is  a  great  divergence  between  different 
animals  in  the  degree  to  which  the  olfactory  sense  is  developed, 
and  with  this  divergence  we  find  corresponding  variations  in  the 
development  of  certain  portions  of  the  brain.  In  those  species  with 
highly  developed  olfactory  sense  the  following  parts  of  the  brain 
show  special  growth  : 

(1)  The  olfactory  lobe,  including  the  olfactory  bulb,  and  the 
olfactory  tract. 

(2)  The  posterior  part  and  the  inferior  surface  of  the  frontal  lobe. 

(3)  The  hippocampal  gyrus  and  the  dentate  convolution. 

(4)  A  convolution  termed  the  bordering  gyrus  and  forming  that 
part  of  the  gyrus  fornicatus  closely  encircling  the  corpus  callosum. 

(5)  The  anterior  commissure. 

The  olfactory  lobe  is  connected  almost  exclusively  with  the  cerebral 
hemispheres  of  the  same  side.  Ferrier  found  that  electrical  excitation 
of  the  hippocampal  region  causes  contortion  of  the  lip  and  nostril  on 
the  same  side,  i.e.  a  reaction  such  as  that  actually  induced  in  these 
animals  by  application  of  an  irritative  or  pungent  odour  direct  to  the 
nostril.  Ablation  experiments  have  not  yielded  very  definite  evidence 
on  the  question  of  localisation  of  the  olfactory  sense.  So  widespread 
are  the  connections  of  the  olfactory  tract  throughout  the  brain  that 


FUNCTIONS  OF  THE  CEREBRiNX  HEMISPHERES     r>o7 

it  would  be  extremely  difficult,  if  ii<»t  impossible,  to  extirpate  all  those 
parts  which  receive  fibres  from  this  tract.  It  is  usual  to  regard  the 
sense  of  taste  as  associated  with  that  of  smell,  but  here  again  experi- 
ment and  clinical  evidence  have  yielded  very  little  that  is  definite. 

GENERAL  CHARACTERISTICS  OF  CORTICAL  MOTOR  FUNCTIONS 
The  motor  phenomena,  which  may  be  observed  as  the  result  of 
artificial  excitation  of  tiie  motor  and  sensory  areas  in  the  cortex, 
constitute  a  very  small  fraction  of  the  activities  which  must  be 
associated  with  the  cerebral  hemispheres.  An  animal  with  its  cerebral 
hemispheres  intact  differs  markedly  from  a  decerebrate  animal  in 
the  variety  of  combined  movements  which  it  may  exhibit,  either 
spontaneously  or  in  response  to  external  stimuli.  When,  however, 
we  excite  the  motor  areas  directly,  we  obtain  movements  which  are 
practically  identical  with  those  which  we  may  elicit  from  a  bulbo- 
spinal animal  by  appropriate  peripheral  stimulation.  The  movements 
thus  excited  from  the  skin  may  be  looked  upon  as  variations  in  the 
tonic  postural  activity  of  the  musculature  of  the  body.  We  have 
seen  that  from  the  end-organs  subserving  deep  and  muscular  sensibility 
(the  proprioceptive  system),  as  well  as  from  the  labyrinth,  impulses 
are  continually  arising  which  travel  up  to  the  spinal  cord,  bulb,  cere- 
bellum, and  mid-brain,  and  excite  a  tonic  activity  of  these  centres. 
The  normal  attitude  of  the  animal  depends  on  the  tonus  thereby  pro- 
duced in  certain  muscles.  Muscular  tone  is  indeed  a  quality  specially 
found  in  certain  groups  of  muscles.  If  the  cerebral  hemispheres  be 
removed,  as  by  a  section  through  the  crura  cerebri  or  in  front  of  the 
mid-brain,  this  postural  tonus  is  increased  and  the  animal  enters  into 
the  condition  of  '  decerebrate  rigidity.'  Destruction  of  one  lab}Tinih 
diminishes  the  tone  on  the  same  side  of  the  body  ;  section  of  all  the 
afferent  nerves  from  a  limb  abolishes  the  tone  in  that  limb,  so  that  its 
posture  thereafter  depends  entirely  on  gravity. 

The  movements  which  are  excited  in  such  animals  by  cutaneous 
stimulation  involve  as  a  necessary  factor  inhibition  of  the  postural 
tone  as  well  as  co-operative  inhibition  of  the  antagonistic  muscles.  In 
the  same  way  excitation  of  the  motor  area  of  the  cortex  has  as  its  most 
essential  feature  an  inhibitory  action  on  the  postural  tonus  in  addition 
to  its  excitatory  action  on  the  muscles  concerned  in  the  movement. 
A  certain  antagonism  is  evident  between  the  total  action  of  the 
cerebral  hemispheres  and  that  of  the  proprioceptive  part  of  the 
central  nervous  system.  Whereas  in  the  decerebrate  animal  there 
is  increased  tonus  in  the  masseters,  in  the  neck  muscles,  the  muscles 
of  the  trunk,  and  the  extensor  muscles  of  the  limbs,  stimulation 
of  the  cortex  produces  opening  of  the  mouth,  flexion  of  the  fore  limb 
or  of  the  hind  limb,  more  easilv  than  anv  other  movements.     That 


508 


PHYSIOLOGY 


an  essential  part  of  this  action  is  inhibitory  is  shown  by  the  effects 
of  exciting  the  motor  area  of  the  cortex  after  exhibition  of  strychnine 
or  during  the  local  action  of  tetanus  toxin.  Whereas  in  the  normal 
animal  closure  of  the  jaw  and  extension  of  the  fore  limb  are  only 
obtainable  from  one  or  two  points  on  the  surface  of  the  brain,  after 

the  injection  has  taken  place, 
every  part  of  the  jaw  area  gives 
closing  of  the  jaw,  every  part  of 
the  arm  area  gives  extension  of 
the  limb  {cp.  Fig.  174). 

Since  the  predominant  in- 
fluence of  the  motor  cortex  is 
therefore  inhibitory  of  the 
stronger  muscles  of  the  body,  as 
well  as  of  the  tonus,  w^hich  is  con- 
tinually and  refiexly  maintained, 
it  is  not  surprising  that  excision 
of  both  hemispheres  should  give 
rise  to  decerebrate  rigidity,  or  that 
destruction  or  division  of 'the  chief 
direct  tracts  from  the  cortex  to 
the  motor  spinal  mechanisms,  viz. 
the  pyramidal  tracts,  should 
determine  increased  tonus  and 
rigidity  of  the  limbs — the  so-called 
'  spastic  '  condition  observed  in 
cerebral  paralyses. 

Two  separable  systems  of  motor 
Fig.  232.    Diagram  (from  Mott  after  Mon-  innervation  appear  thus  to  control 

AKOW)  to    show  the    interaction    of    the  <•  i  r\ 

different    levels   in   the    central    nervous  two  sets  ot  nmSCUlature.   Une  SVS- 

systcm  in  the  production  of  co-ordinated  ^^^^^  exhibits  the  transient  phases 

volitional     movements.  .  .  .  * 

s,  .sensory  neuron;   B,  bulb;    TH,  thala-  of  heightened  reaction  whlch  COn- 

mus ;     MA,    motor    area ;     P,    pyramidal  gtitute    leflex    movements  ;      the 
fibre  ;       c,     cerebello  -   pontine     nuclei  ;      , ,  ■    ^    •       ^^     .     .       ^     i.      • 

vs,  vestibular  neuron  (Deiters'  nucleus),     other  maintains  that  steady  tonic 

response  which  supplies  the 
muscular  tension  necessary  to  attitude.  Hughlings  Jackson  long 
ago  called  attention  to  this  contrast  between  the  two  systems.  He 
pointed  out  that  while  the  cerebrum  innervates  the  muscles  in  the 
order  of  their  action  from  the  most  voluntary  movements  (the  limbs) 
to  the  most  automatic  (trunk),  the  cerebellum,  or,  as  we  should  say 
now,  the  whole  proprioceptive  system,  innervates  them  in  the  opposite 
order.  The  cerebelliun  therefore  he  regarded  as  the  centre  for  con- 
tinuous movements  and  the  cerebrum  for  changing  movements. 
The  increased  tone  of  the  paralysed  muscles,  observable  after  hemi- 


FUNCTION'S  OF  THE  CEREBRAL  HEMISPHERES      -IDO 

ple^ia,  he  ascribed  to  unbalanced  cerebellar  influence.  While  there 
is  no  doubt  that  the  cerebellum  must  play,  and  does  play,  a 
considerable  part  in  the  production  of  decerebrate  rigidity  and 
of  the  spastic  condition  of  hemiplegia,  it  is  not  the  only  element 
involved ;  nor  is  it  essential,"  since  decerebrate  rigidity  may 
continue  after  extirpation  of  the  cerebellum  and  an  exaggerated 
knee-jerk  may  result  from  section  of  the  spinal  cord  in  the  lower 
cervical  region. 

HIGHER  ASSOCIATIVE  FUNCTIONS  OF  THE  CORTEX 
The  smiple  and  uncomplicated  nature  of  the  movements  elicited 
on  cortical  stimulation  shows  that  we  cannot  regard  these  motor 
centres  as  responsible  for  the  whole,  or  even  the  greater  part,  of  the 
motor  functions  of  the  cortex.  They  are  in  fact  simply  the  starting- 
point  for  the  motor  impulses  which  run  down  the  long  pyramidal 
tracts,  but  which  result  from  the  acti\nties  of  the  cerebral  hemi- 
spheres as  a  whole.  In  the  lower  mammals  they  do  not  even  repre- 
sent the  only  starting-point,  as  is  shown  by  the  almost  perfect  recovery 
of  volitional  motor  power  in  a  dog  deprived  of  its  motor  cortex. 
The  distinguishmg  feature  of  the  response  of  an  animal  possessing 
cerebral  hemispheres  is  that  it  is  not  determined  solely  and  exclu- 
sively by  the  nature  and  position  of  the  peripheral  stimulation,  but 
involves  elements  connected  with  the  past  experiences  of  the  animal, 
and  including  therefore  the  results  of  previous  stimulation  of  many 
of  the  sense-organs,  either  directly,  or  indirectly  as  a  result  of  reflex 
movements.  The  animal's  reactivity  is  determined  by  the  past 
history  of  the  animal,  and  this  modifying  influence  on  the  brain 
must  involve  parts  connected  with  all  its  sense-organs.  In  any 
conscious  motor  act  we  may  say  therefore  that  the  brain  acts  as  a 
whole,  or  nearly  as  a  whole. 

In  endeavouring  to  arrive  at  some  idea  of  the  neural  processes 
concerned  in  volitional  movements,  i.e.  movements  of  the  intact 
animal,  we  are  dealing  with  events  which  in  ourselves  come  within 
the  sphere  of  consciousness,  so  that  some  assistance  is  derived  by 
appealing  to  our  own  mental  experiences.  Especially  is  this  necessary 
in  the  case  of  the  ft-en.sations.  It  might  be  imagined  that  a  simple 
sensation  would  ensue  as  the  result  of  local  stimulation,  say  of  the 
visual  centre  on  one  side.  Our  knowledge  of  the  properties  of  the 
systems  of  neurons  composing  the  central  nervous  system  would 
teach  us  that  no  excitatory  process  could  remain  confined  to  one 
portion  of  the  brain,  but  must  diverge  in  many  direction-^.  It  is 
true  that  excision  of  the  occipital  lobes  on  one  side  causes  blindness 
to  objects  in  the  opposite  half  of  the  field  of  vision.  This  is,  however, 
merelv  a  result  of  localisation  of  the  end  of  visual  fibres,  and  the 


510  PHYSIOLOGY 

same  effect  can  be  broiitiht  about  by  division  of  the  right  optic  tract, 
or  damage  to  the  right  half  of  both  retinae. 

On  the  other  hand,  an  appeal  to  our  own  experience  shows  that 
no  sensation  can  be  regarded  as  simple,  i.e.  as  following  merely 
stimulation  of  visual  fibres  or  visual  centres.  Thus  the  sensation 
of  a  luminous  point  has  connected  with  it  not  only  luminosity  but 
also  colour  and  intensity.  Moreover  the  apparent  position  of  the 
luminous  point  comes  into  consciousness  at  the  same  time  as  the 
consciousness  of  the  luminosity  itself,  and  this  location  of  the  stimu- 
lation involves  muscular  impressions  from  the  eyeballs  and  an 
association  between  certain  points  on  the  retina  and  certain  corre- 
sponding muscular  movements  of  the  eye  muscles,  of  the  head  and 
neck,  and  even  of  the  body  and  arm — movements  which  would  be 
necessary  to  bring  the  image  of  the  spot  on  to  the  fovea  centralis 
and  to  approach  the  whole  body  to  the  site  of  the  stimulating  object. 

As  the  visual  sensation  becomes  more  complex  the  associated 
sensations  and  experiences  which  it  evokes  become  more  numerous. 
Thus  the  image  of  a  chair  falling  on  the  retina  excites  a  long  train 
of  nervous  processes.  At  once  we  become  aware  not  only  of  a  visual 
impulse  but  of  an  object  which  possesses  colour,  extension,  or  size 
in  three  dimensions,  solidity,  hardness,  distance  or  position  in 
space,  &c.  These  qualities  are  founded  on  past  experiences— visual, 
muscular,  and  tactile.  Moreover  we  are  at  once  aware  of  the  uses 
of  the  chair,  and  of  its  name  both  spoken  and  written,  a  mental  activity 
connoting  revival  of  higher  visual  and  auditory  sensations.  The  higher 
in  the  scale  of  intelligence,  the  greater  is  the  development  of  the 
cerebral  hemispheres  and  the  more  extensive  are  the  associations 
arising  in  connection  with  any  single  sense  impression. 

Besides  the  portions  of  the  brain  which  send  out  the  motor  paths 
and  which  receive  the  endings  of  the  sensory  paths,  there  may  be 
whole  regions  taken  up  by  the  interconnecting  neurons  which 
subserve  the  association  of  the  activities  of  all  parts  of  the  cerebral 
hemispheres,  and  the  higher  the  animal  is  in  the  scale  of  intelligence 
the  larger  must  be  the  relative  amount  of  brain  substance  set  apart 
for  these  functions  of  association.  This  is  very  evident  if  we  compare 
the  brain  of  three  animals,  such  as  the  dog,  the  ape,  and  man. 
Although  as  we  ascend  to  man  there  is  an  absolute  increase  in  the 
amount  of  brain  substance  involved — say  in  the  motor  areas  or  in 
the  sensory  areas — the  increase  is  very  small  as  compared  with  that 
in  those  portions  of  the  brain  which  give  no  response  on  stimulation, 
and  in  man  these  '  silent '  parts  of  the  brain  form  the  greater  part 
of  the  cerebral  cortex.  Although  every  phase  of  cerebral  activity, 
every  conscious  event,  involves  co-operation  of  a  large  number  of 
distant  portions  of  the  brain  substance,  in  most  of  them  there  will  be 


FUNCTIONS  OF  THE  CEREBRAL  HEMISPHERES      511 

some  seat  of  sense  impressions  which  will  be  predominant,  and  a  train 
of  ideas  may  be  specially  visual,  or  auditory,  or  tactile.  It  is  therefore 
not  surprisinf^  that  in  the  immediate  neighbourhood  of  the  cortical 
areas  which  receive  the  endings  of  the  sensory  tracts  association 
areas  are  developed  which  may  be  labelled  according  to  the  sense- 
organ  with  which  they  are  most  nearly  in  relation.  Thus  we  may 
speak  of  the  visual-sensory  and  the  visual  association,  or  psychical 
area,  the  auditory-sensory  and  the  auditory-psychical,  and  so  on. 
The  limits  of  these  areas  are  indicated  in  Fig.  222,  p.  489. 

THE  FUNCTION  OF  SPEECH 
The  acts  of  a  conscious  individual,  i.e.  one  possessing  cerebral 
hemispheres,  are  determined  by  his  experience.  The  wider  the 
range  of  past  sense  impressions  which  can  be  called  up  and  taken 
into  the  chain  of  processes  involved  in  any  reaction — the  more,  that 
is  to  say,  the  individual  weighs  his  acts  in  the  light  of  past  expe- 
rience— the  more  fitted  will  these  acts  be  to  his  maintenance  amid 
the  ever-changing  stresses  of  the  environment.  In  this  guiding  of 
behaviour  by  experience  man,  as  well  as  the  higher  mammals,  may 
profit  also  from  accumulated  racial  experience.  The  increased  com-* 
plexity  of  the  neural  processes  concerned  in  every  reaction  of  the  body, 
and  the  excessive  lost  time  brought  about  by  the  intercalation  of  one 
neuron  after  another  in  the  chain  of  the  excitatory  process,  would 
finally  counteract  the  advantages  derived  from  the  growth  in  com- 
plexity of  the  brain,  were  it  not  that,  as  a  result  of  education  or  training, 
slwrt  cuts  are  laid  down,  by  means  of  which  reactions  adapted  to  the 
maintenance  of  the  individual  can  be  carried  out  immediately,  without 
thought  and  without  correlated  calling  up  of  numberless  sense  impres- 
sions. Education  in  fact  consists  in  laying  down  these  '  short  cuts  ' 
which,  as  habits,  are  the  basis  of  the  behaviour  of  the  animal.  The 
more  complex  the  central  mechanism  and  the  wider  the  range  of 
environmental  change  to  which  adaptation  is  necessary,  the  longer 
must  be  the  time  involved  in  this  process  of  road-making  within  the 
cerebral  hemispheres.  The  behaviour  of  man  is  therefore  a  product 
of  many  years'  training,  during  which  time  he  is  in  a  state  of  subjection 
and  unfit,  from  the  absence  of  habit,  to  maintain  himself  as  a  unit 
in  the  human  community.  The  neural  short  cuts  of  habit  are, 
however,  only  of  advantage  to  the  individual  in  dealing  with  those 
events  which  are  of  every-day  occurrence.  Every  novel  circumstance 
must  involve  a  revival  of  past  sense  impressions  and  a  calling  up 
of  activities  of  the  most  diverse  portions  of  the  brain  in  order 
to  arrive  at  the  safest  or  most  advantageous  mode  of  action 
adapted  to  the  circumstances.  Here  again  the  com})loxity  of  the 
process  would,  by  the  very  delay  involved,  put  a  stop  to  a  further 


512  PHYSIOLOGY 

rise  in  intellectual,  i.e.  associative,  capacities,  were  it  not  for  the 
invention  of  Speech. 

In  speech  we  have  a  symbolism  which  acts  as  an  economy  of 
thought  or  of  cerebral  activities.  An  object,  such  as  a  table,  with 
its  associated  properties  of  colour,  consistence,  spatial  extension, 
and  resistance,  with  the  connoted  acts  associated  with  its  use,  can 
now  be  evoked  as  a  word,  involving  comparatively  simple  auditory 
and  motor  processes,  which  itself  may  be  employed  as  a  unit  of 
thought  and  brought  into  connection  with  other  words,  each  of  which 
in  the  same  way  is  the  symbol  for  a  whole  scries  of  sensory  and  motor 
processes.  The  training  of  the  cultivated  man  consists  in  a  constant 
extension  of  the  range  of  this  symbolism,  and  the  acquisition  of  words 
including  wider  and  wider  groups  of  neural  processes,  so  that  finally 
we  arrive  at  those  short  verbal  collections  which,  as  the  so-called 
natural  laws,  summarise  the  experience  not  only  of  the  individual 
but  such  as  is  common  to  the  whole  race  of  mankind.  All  science 
may  in  fact  be  regarded  as  an  extension  of  the  process  of  representa- 
tion of  neural  experience  in  symbolic  shorthand,  which  in  the  child 
begins  with  the  utterance  of  such  a  simple  word  as  '  mamma,'  and  from 
tv^hich  speech  has  arisen.  A  study  of  the  nervous  mechanisms  involved 
in  speech  is  therefore  of  interest  in  its  relations  to  the  development 
of  the  intelligence,  and  helps  us  to  realise  more  completely  the 
conditions  which  determine  the  activity  and  functioning  of  the 
cerebral  hemispheres.  Much  light  is  thrown  upon  this  mechanism 
by  the  study  of  disorders  in  man  grouped  together  under  the  name 
Aphasia. 

It  has  been  usual  to  divide  the  disorders  of  speech  known  as  aphasia 
into  various  groups,  as  follows  : 

(1)  Motor  aphasia,  or  aphasia  of  Broca.  In  this  condition,  which 
was  described  fully  by  Broca  and  referred  by  him  to  a  lesion  of 
the  third  left  frontal  convolution,  the  patient  is  unable  to  speak, 
although  he  understands  what  is  said  to  him  and  has  been  stated 
to  suffer  from  no  impairment  of  his  intelligence. 

(2)  Sensory  aphasia,  or  aphasia  of  Wernicke.  This  condition  was 
connected  by  Wernicke  with  the  existence  of  lesions  in  a  fairly  wide 
area,  known  as  the  area  of  Wernicke,  which  involves  the  supra- 
marginal  and  angular  gyri  and  the  hinder  portions  of  the  first 
and  second  temporo-sphenoidal  convolutions.  In  these  cases  there 
may  be  limited  power  of  speech,  but  there  is  serious  impairment  of 
the  intelligence  and  especially  of  the  power  of  a])preciation  of  spoken 
words,  so  that  the  patient  does  not  understand  what  is  said  to  him. 
This  condition  may  or  may  not  be  attended  with  alexia,  loss  of  power 
CO  read.  Any  impairment  of  the  motor  processes  of  speech  which 
is  present  is  due  rather  to  the  inability  of  the  patient  to  appreciate 


FUNCTIONS  OF  THE  CEREBRAL  HEMISPHERES      5 Li 

what  he  himself  is  saying,  so  that  there  is  here  a  species  of  sensory 
paralysis  in  the  higher  sphere  of  neural  processes. 

(3)  Anarthria.  This  is  a  condition  in  which  there  is  marked 
impairment  of  the  motor  powers  of  expression,  although  intelligence 
and  appreciation  of  speech,  both  spoken  and  written,  may  be  un- 
altered. This  condition  is  generally  associated  with  lesion  of  the 
white  matter  of  the  external  capsule  as  it  passes  round  the  lenticular 
nucleus. 

There  are,  however,  considerable  difficulties  in  the  acceptation  of 
this  traditional  classification.  Microscopic  examination  of  Broca's 
convolution  shows  a  type  of  cortex  entirely  different  from  that  part, 
viz.  the  psycho-motor  area  of  the  ascending  frontal  convolution, 
which  is  concerned  with  the  higher  cerebral  processes  resulting  in 
movement.  Its  structure  is  in  fact  identical  with  that  described 
by  Campbell  as  the  '  intermediate  precentral  area  '  and  regarded 
as  characteristic  of  the  association  areas.  Moreover  it  is  difl&cult 
to  comprehend  how  a  function  such  as  speech,  with  its  enormously 
complex  mechanism,  could  be  limited  to  so  small  a  portion  of  the 
brain  as  Brocas  convolution.  The  neural  basis  of  language  must  in 
fact  be  co-extensive  with  the  sensory  centres  (the  projection  spheres) 
and  with  the  whole  region  of  lower  association.  We  might  indeed 
speak  of  auditory  and  \asual  word-centres  as  located  in  the  visuo- 
psychical  and  auditory  psychical  centres.  There  is  probably, 
however,  no  word,  still  less  a  collection  of  words,  expressing  an  idea, 
which  does  not  involve  the  activity  of  practically  all  parts  of  the 
cerebral  cortex.  As  Bolton  *  points  out,  '"  a  word,  such  as  '  mouse,' 
at  once  sets  in  effect  processes  of  association  which  pass  to  every 
projection  sphere  with  the  solitary  exception  of  the  gustatory,  and 
even  this  may  be  aroused  in  a  person  who  has  eaten  a  fried  mouse  in 
the  hope  of  thereby  recovering  from  an  attack  of  whooping-cough." 

A  careful  examination  of  an  extensive  series  of  cases  by  Marie 
has  shown,  in  fact,  that  Broca's  aphasia  does  not  exist  as  a  result 
of  lesions  of  Broca's  convolution.  This  part  of  the  brain  may  be 
destroyed  without  any  disorder  of  speech;  The  cases  described  by 
Broca  of  motor  aphasia  are  really  cases  of  sensory  aphasia  from 
lesion  of  Wernicke's  area,  combined  with  anarthria  due  to  subcortical 
injury  of  the  fibres  of  the  internal  capsule.  The  statement  that  there 
is  no  loss  of  intelligence  in  these  cases  of  so-called  motor  aphasia 
does  not  bear  investigation.  Although  as  patients  they  niay  comport 
themselves  reasonably,  as  soon  as  they  have  to  perform  any  duties 
which  have  been  learnt  by  them  in  connection  with  their  ordinary 
avocations  they  show  their  deficiency.  They  are  incapable  of 
transacting  ordinary  business,  at  any  rate  to  the  extent  to  which 

*  In  his  admirable  article  in  Hill's  "  Further  Advances  in  Physiology." 

33 


514  PHYSIOLOGY 

they  were  before  the  lesion.  The  amount  of  impairment  of  intelligence 
will  vary  in  different  cases  according  to  the  extent  of  the  lesion. 
Thus  softening  generally  affecting  the  occipital  lobe  may,  with 
hemianopia,     cause     '  word- blindness,'    or   alexia,    a    loss    of    power 

Amentia  Dementia 


Fig.  233.  Types  of  lesions  giving  rise  to  deficient  intellectual  power. 
In  amentia,  the  deficiency  is  due  to  failure  of  development ;  in 
dementia,  to  atrophy  of  the  cells  (especially  small  pyramidal) 
previously  present  in  the  cortex.     (Mott.) 

of  appreciating  the  meaning  of  pronounced  or  written  words.  In 
most  individuals,  and  certainly  in  the  uneducated,  this  power  may 
be  cut  out  altogether  without  interfering  considerably  with  the 
mental  powers.  On  the  other  hand,  from  babyhood  upwards  we 
have  learnt  the  meaning  of  words  and  their  grouping  by  auditory 
impressions.  If  the  whole  of  the  auditory  associations  be  destroyed 
by  an  extensive  lesion  in  the  first  and  second  temporal  convolutions 


FUNCTIONS  OF  THE  CEREBRAL  HEMISPHERES     515 

the  resulting  loss  of  word  appreciation,  sensory  aphasia,  will  be 
attended  with  great  diminution  of  mental  powers.  It  must  be  remem- 
bered that  the  area  of  Wernicke  is  not  a  sensory  centre,  but  a  centre 
of  association  between  the  various  sense -impressions,  especially  those 
of  hearing  and  sight.  It  may  therefore  be  spoken  of  as  an  intellectual 
centre.  Pure  motor  apha^  of  course  exists,  but  is  always  anarthria 
and  is  due  to  a  lesion  in  the  lenticular  zone,  i.e.  in  the  lenticular  nucleus 
and  its  neighbourhood,  in  the  anterior  part  and  the  genu  of  the  internal 
capsule,  and  possibly  in  the  external  capsule.  H 

It  is  important  to  make  a  distinction  between  loss  of  sanity  and 
loss  of  intellectual  powers.  ,''|'he  essential  factor  of  sensory  apjiasia  is 
the  existence  of  intellectual  impairment,  though  in  his  behaviour 
the  patient  may  appear  perfectly  normal.  On  the  other  hand,  in 
insanity  there  may  be  perfect  retention  of  the  intellectual  processes, 
which  depend  on  the  proper  working  of  the  lower  association,  centres. 
The  personality  of  the  individual,  and  therefore  finally  his  behaviour, 
involves  a  further  association  on  a  higher  plane  of  these  intellectual 
processes  and  therefore  control  in  accordance  with  the  relation,  past, 
present,  or  future,  of  the  individual  to  his  environment.  The  pre- 
frontal region  is  in  all  probability  the  seat  of  this  highest  plane  of 
association.  Insanity  always  involves  alteration  of  personality  and 
depends  on  failure  of  development  or  on  disintegration  processes 
(subevolution  or  dissolution  of  this  region)  (Fig.  233).  In  monkeys 
and  cats  Franz  has  found  that  destruction  of  the  frontal  lobes  causes 
a  loss  of  recently  formed  habits.  He  concludes  from  his  experiments 
that  the  frontal  lobes  are  the  means  by  which  we  are  able  to  learn  and 
to  form  habits,  i.e.  to  regulate  our  behaviour  in  accordance  with  the 
needs  of  our  position  in  society. 

THE  TIME  RELATIONS  OF  CENTRAL  NEURAL  REACTIONS 
In  the  spinal  animal  a  stinmlus  of  any  particular  quahty  and  locah  ■ 
sation  always  evokes  an  appropriate  reaction.  A  certain  period  of 
time  necessarily  elapses  between  the  moment  at  which  the  stimulus 
is  applied  and  the  moment  at  which  the  resulting  reaction  takes  place. 
This  interval  is  spoken  of  as  the  simple  reaction  time,  and  in  the  spinal 
animal  is  entirely  independent  of  consciousness.  Many  reactions, 
even  in  the  intact  animal,  are  also,  as  we  may  say,  involuntary  and  are 
not  modified  perceptibly  by  our  consciousness  of  their  occurrence  : 
such  reflexes  as  the  withdrawal  of  the  hand  when  it  comes  in  contact 
with  a  hot  surface,  the  shutting  of  the  eyelid  when  the  conjunctiva 
is  touched,  the  drawing  up  of  the  leg  when  the  sole  of  the  foot  is  tickled. 
Not  only  are  these  carried  out  in  the  absence  of  voluntary  impulses, 
but  in  many  cases  it  is  almost,  if  not  quite,  impossible  to  check  the 
reaction  by  any  effort  of  the  will. 


516  PHYSIOLOGY 

When  the  leg  is  drawn  up  in  response  to  a  painful  or  nocuous 
stimulus  applied  to  the  foot,  a  certain  amount  of  time  is  involved 
in  each  of  the  following  links  in  the  chain  of  processes  which  determine 
the  reaction : 

(1)  The  conversion  in  the  peripheral  sense-organ  of  the  mechanical 
stimulus  into  a  nerve  process. 

(2)  The  passage  of  a  nerve  impulse  up  the  nerve  from  the  end 
organ  to  the  spinal  cord. 

(3)  The  passage  of  the  impulse  across  two  or  more  synapses  in  the 
grey  matter  of  the  cord. 

(4)  The  passage  of  the  impulse  down  the  motor  nerve  fibres  from 
the  spinal  cord  to  the  muscles. 

(5)  The  processes  occurring  in  the  end-organs  of  the  muscle. 

(6)  The  latent  period  in  the  muscle  fibre  itself. 

With  a  weak  stimulus  No.  1  is  impossible  to  measure.  With 
a  strong  stimulus  it  may  be  so  short  as  to  be  practically  negligible. 
(2),  (4).  (5),  and  (6)  represent  quantities  for  the  measurement  of  which 
we  have  all  the  necessary  data. 

In  any  given  reflex  therefore  we  may  add  these  periods  together 
and  subtract  them  from  the  total  reaction  time  ;  we  thus  get  a 
'  reduced  reaction  time,'  which  represents  the  time  involved  in  the 
passage  of  the  impulse  through  the  central  nervous  system,  and 
in  the  conversion  of  an  afferent  impulse  into  an  aggregate  of  co- 
ordinated motor  impulses,  l^/is  found  that  the  reduced  reaction 
time  accounts  for  the  greater  part  of  the  total  reaction  time. 
Since  we  have  no  reason  to  assume  that  the  rate  of  passage  of 
an  impulse  through  the  intra-spinal  course  of  a  nerve  fibre  differs 
appreciably  from  the  rate  at  which  it  is  conducted  by  the  same  nerve 
fibre  outside  the  cord,  the  extra  delay  which  occm-s  in  the  passage 
of  the  impulse  through  the  cord  must  take  place  either  in  the  nerve- 
cells  themselves,  or  in  the  synapses,  through  which  the  impulse 
passes  from  one  neuron  to  the  next  in  the  chain  of  reflex  elements. 

The  rate  of  passage  of  an  impulse  through  the  nerve- cell  can 
only  be  determined  in  one  part  of  the  body,  viz.  in  the  posterior 
spinal  root  ganglia,  since  only  in  these  is  it  possible  to  detect  the 
moment  of  passage  of  an  impulse  across  a  given  section  of  a  nerve 
fibre  on  both  sides  of  the  ganglion-cell  in  which  the  nerve  fibres  arise. 
Experiments  on  this  point  have  been  made  by  Steinach  and.  by 
Moore.  In  each  case  the  time  occupied  in  the  passage  of  the  impulse 
through  the  ganglion  was  not  appreciably  longer  than  if  the  impulse 
had  passed  through  a  corresponding  stretch  of  uninterrupted  nerve 
fibre.  We  are  therefore  justified  in  concluding  that  the  relatively  great 
delay  in  the  passage  of  an  impulse  through  the  central  nervous  system 
has  its  seat  in  the  synapses  across  which  the  impulse  has  to  pass. 


FUNCTIONS  OF  THE  CEREBRAL  HEMISPHERES      517 

This  conclusion  is  in  accordance  with  our  experience  on  the  latent 
period  of  muscle,  the  greater  part  of  which  is  due  to  changes  occurring 
in  the  nerve-endings,  i.e.  in  the  synapses  between  motor  nerve  and 
muscle.  The  greater  the  number  of  s}Tiapses  involved  in  any  given 
reaction,  i.e.  the  greater  the  complexity  of  the  reaction^^fclonger  will 
be  the  period  which  elapses  between  the  moment  of  ap^Mition  of  the 
stimulus  and  the  moment  at  which  the  response  takes  place .  Espe- 
cially is  this  the  case  when  the  complex  meshwork  of  neurons  of  the 
cerebral  hemispheres  is  involved,  or  when  the  occurrence  of  the  reaction 


Fig.  234.     Arrangement  of  apparatus  for  cktermination  of   reaction   time. 
(Alcock  and  Ellison.) 

R,  coil ;  E,  exciting  electrodes ;  f,  tuning-fork;  a,  b,  kej-s  ;  s,  t,  electro- 
magnetic signals  ;  D,  drum. 


is  associated  with  the  conscious  processes  of  sensation  and  volition. 
In  the  latter  case  the  determination  of  the  reaction  time  has  the  added 
interest  that  it  gives  information  as  to  the  time-relations  of  the  psychical 
processes  which  are  the  representation  in  consciousness  of  the  physio- 
logical changes  occurring  in  the  neurons  of  the  central  nervous  system. 

Many  methods  are  employed  for  the  measuring  of  the  reaction 
time  of  conscious  processes.  In  most  methods  the  application  of 
the  stimulus  is  arranged  so  as  to  close  the  circuit  of  a  current  which 
flows  through  an  electro-magnet  activating  a  lever  which  writes 
on  a  rapidly  moving  blackened  surface.  The  reaction  of  the  individual 
who  is  the  subject  of  experiment  is  arranged  so  that  the  resulting 
movement  activates  a  key  by  which  the  same  current  is  opened.  We 
thus  obtain  a  tracing  on  the  blackened  surface  showing  the  moment 


518  PHYSIOLOGY 

of  application  of  the  stimulus  and  the  moment  at  which  the  reaction 
takes  place.  Thus,  if  the  reaction  time  for  an  auditory  stimulus  is  to 
be  determined,  the  electric  current  is  arranged  so  as  to  pass  through  : 

(1)  A  spring  contact  key  which  can  be  pressed  so  as  to  make  a 
noise.        ^"^ 

(2)  An  eleCTric  signal  writing  on  a  rapidly  moving  surface. 

(3)  A  second  key,  which  the  subject  will  release  as  soon  as  he 
hears  the  noise  of  the  first  key  and  so  break  the  current. 

The  recording  surface  may  be  a  drum,  a  pendulum  myograph, 
or  a  spring  myograph,  such  as  the  '  shooter  '  of  du  Bois-RajTuond. 
If  the  sensory  impression  is  to  be  from  the  skin  the  current  may 
be  made  to  pass  through  the  primary  coil  of  an  inductorium,  and 
wires  be  taken  from  the  second  coil  to  some  part  of  the  surface  of 
the  skin.  In  this  case  the  signal  may  be  started  by  opening  the 
circuit,  and  the  subject  of  the  experiment  will  respond  by  closing  the 
circuit  by  means  of  a  spring  key  directly  he  feels  the  shock  caused  by 
the  break  of  the  primary  circuit.  If  the  reaction  period  is  to  be 
determined  for  sight  a  white  piece  of  paper  may  be  placed  on  an 
electro-magnet  in  the  primary  circuit  and  the  person  vnW  respond 
directly  he  sees  this  move.  Many  other  instruments  have  been  devised 
for  the  same  purpose.  The  average  reaction  times  obtained  with  the 
different  senses  are  as  follows  : 

Electrical 
Sight  Hearing  stimulation  of  skin 

0-186  to  0-222  sec.        0-115  to  0-182  sec.        0-117  to  0-201  sec. 

The  two  figures  given  for  each  case  are  the  extremes  obtained 
in  different  series  of  observations. 

The  times  vary  according  to  the  condition  of  the  person  that  is  the 
subject  of  the  experiment.  They  are  lengthened  by  fatigue  ;  they 
are  shortened  up  to  a  certain  point  by  continued  practice.  Within 
limits  also  they  are  shortened  by  increase  of  the  strength  of  the  stimulus. 

DILEMMA.  When  the  subject  has  to  make  a  deliberate  choice 
between  the  parts  of  the  body  stimulated  the  reaction  time  is  con- 
siderably longer.  To  show  this,  the  wires  from  the  secondary  coil  are 
connected  by  a  switch  to  two  pairs  of  electrodes  which  are  applied, 
one  to  the  right  and  one  to  the  left  half  of  the  body.  It  is  agreed 
beforehand  that  the  subject  shall  react  only  to  stimulation,  say, 
of  the  right  side.  The  switch  is  removed  from  the  observation  of 
the  subject  and  the  stimulus  is  apphed  irregularly  to  one  side  or  to 
the  other.  It  is  found  that  the  additional  neural  processes  invoh  ed 
in  determining  whether  the  stimulus  is  on  the  right  side,  and  therefore 
should  be  followed  up  as  agreed,  adds  considerably  to  the  length 
of  the  reaction  time   (on  an  average  '066  sec).     It  is  possible  to 


FUNCTIONS  OF  THE  CEREBRAL  HEMISPHERES     519 

complicate  tlie  dilemma  to  almost  any  extent.  Thus  the  experiment 
may  be  so  arranged  that  either  a  red  or  a  white  disc  appears  and  the 
subject  has  to  react  with  the  right  hand  to  the  red  disc  and  with  the 
left  hand  to  the  white  disc.  In  such  an  experiment  the  reaction  time 
was  found  to  be  0-154  sec.  longer  than  the  simple  reaction  time.  A 
still  more  complex  process  would  be  involved  in  the  experiment  in 
which  a  word  was  spoken,  and  the  subject  had  to  speak  some  other 
word  which  had  some  association  with  the  word  which  formed  the 
stimulus,  e.g.  horse — mammal ;  paper — pen,  &c.  In  such  an  experi- 
ment the  reaction  time  was  found  to  be  as  long  as  0'7  to  0-8  sec. 

We  see  that  the  recording  of  the  time  of  occurrence  of  any  physical 
event  can  only  occur  after  a  certain  lost  time,  which  represents  the 
observer's  reaction  time  for  the  stimulus  in  question.  This  only 
applies,  however,  to  movements  carried  out  in  response  to  single 
stimuli;  01  to  stimuli  repeated  at  irregular  intervals.  When  the 
stimuli  are  rhythmic  the  lost  time  only  applies  to  the  first  one  or 
two  of  the  stimuli.  The  observer  or  subject  is  conscious  of  the 
interval  elapsing  between  the  physical  event  and  his  reaction,  and 
anticipates  the  later  stimuli  so  that  his  reaction  becomes  synchronous 
with  the  stimulus.  This  synchronism  of  stimulus  and  reaction 
characterises  all  rh}'thmic  movements,  such  as  dancing  or  the  playing 
of  an  orchestra  in  time  with  the  beat  of  the  conductor's  baton. 


SFXTION  XVIII 

THE  VISCERAL  OR  AUTONOMIC  NERVOUS 
SYSTEM 

In    the    medulla    oblongata    it    is  easy  to  differentiate  the  central 

grey  matter  connected  with  the  peripheral  nerves  into  two  categories, 

viz.    splanchnic    and    somatic.     Each   of   these   two  sets   of   nerves 

possesses   both   afferent  and  efferent  fibres.     Gaskell  has  suggested 

that  the  same  arrangement  would  hold  for  any  typical  segmental 

nerve,  which  would   therefore  have   four  roots,  viz.  two  somatic— 

the   motor   and  sensory  roots   distributed   to   the   skin   and   skeletal 

muscles — and   two   splanchnic   roots,  also   motor   and   sensory,  and 

composed    of    small   fibres  distributed  to  the  viscera   or  structures 

which  are  visceral  in  origin  [e.g.  developed  from  the  branchial  arches). 

In  the  medulla  the   somatic  efferent  fibres,  such  as  the    sixth  and 

twelfth  nerves,  arise  from  the  column  of  large  cells  lying  in  the  floor 

of   the   fourth   ventricle   close   to   the   middle   line.     The   splanchnic 

fibres,   e.g.   those   of    the  facial    and    vago-glossopharyngeal    nerves, 

arise  from  a  column  of  cells — the  nucleus  ambigTius  and  facial  nucleus. 

lying  more  laterally  and  deeper,  below  the  surface  of  the  ventricle. 

The  motor  root  of  the  fifth  would  also  belong  to  the  same  system. 

In  the  spinal  cord  the  visceral  fibres  arise  in  the  cells  of  the  lateral 

horn,  i.e.  from  a  situation   corresponding  to  the  splanchnic    motor 

nuclei  of  the  pons  and  medulla.     Whereas,  however,  the  splanchnic 

afferent    nerves,    such    as    the    glossopharyngeal;    and    perhaps   the 

sensory  nucleus  of  the  fifth,  form  a  well-marked  splanchnic  system 

of  nuclei  in  the  medulla,  in  the  cord  the  afferent  fibres  from  the  viscera 

pass  in  with  the  other  afferent  somatic  fibres,  and  their  immediate 

connections  in  the  cord  are  as  yet  unknown. 

The  autonomic  system  of  nerves  includes  the  s}Tnpathetic  system 

(properly  so   called)  and    some   of  'the    cranial    and   sacral    nerves. 

The    sympathetic    system    (Fig.  235)  is    composed  of    a    chain   of 

ganglia  lying  each  side  of  the  vertebral  column,  there  being  as  a 

rule  one  ganglion  to  each  spinal  nerve-root.     In  the  cervical  region 

these  ganglia  are  condensed  into  two,  the  superior  and  inferior  cervical 

ganglia,  united  by  the  cervical  sympathetic  trunk  ;    and  the  upper 

three  or  four  thoracic  ganglia  on  each  side  are  condensed  to  form  the 

520 


Sup.cerv.g 


Inf  cerv.g.^ 


^72:=0     /^rm 


C.i 
2 
3 


3  \  Head  &  Neck 
'4 


>Arm 


Abdominal 
Viscera 


(L., 


J   ^-L-eg 


S.I 


Hypogastric  n     pgjy  vjsc.n. 


Vrn  2-^5      Di  v-rammatic  representation  of  tho  di.tribut.ou  of  the  sympathetic  syst.ui. 

'  ''•  '^The^r  Lea  repre'sent  the  r^^^^^ Sr^t^^:^^^^^^^ 
making  up  the  white  rami  ^^"^'^".'"jff  °J*^;  ;^^te  is  ind^^^^^^ 
printed  in  red.  ,Pn  the  extreme  right  o    the  b^^^^^  ^J^^  ^^^  double 

bution  of  the  white  rami  a"«^"g/^°^^^'"/'^^'?ho  limb  plexuses.      H.    heart  ; 
brackets  point  to   the   nerve-roots   making    "jJ^er 
s.  stomach  ;   i,  small  intestme  ;    c,  colon  ;    B.  bladder. 


522 


PHYSIOLOGY 


stellate '  ganglion.  At  the  bottom  of  the  chain  there  is  only  one 
coccygeal  ganglion  for  the  coccygeal  vertebrae. 

In  the  abdomen  is  a  second  system  of  ganglia,  in  special  connection 
with  the  abdominal  viscera,  lying  in  front  of  the  aorta  and  surromiding 
the  origins  of  the  large  arteries  to  the  alimentary  canal.  These  are 
the  semilunar  or  solar  ganglia,  the  superior  mesenteric  and  the  inferior 
mesenteric  ganglia. 

In  the  organs  themselves  we  find  a  third  system  of  ganglion-cells, 
either  scattered  or  collected  to  form  small  ganglia.  These  isolated 
ganglion  cells  as  a  rule  have  no  connection  with  the  fibres  of  the 


Fig.  236.  Diagram  of  spinal  segment  with  its  nerve- 
roots,  somatic  and  visceral.  (G.  D.  Thane.) 
(The  visceral  roots  are  represented  in  red.) 

sympathetic  system,  but,  as  we  shall  see  later,  lie  on  the  course  of 
the  impulses  descending  by  other  nerves  of  the  autonomic  system, 
e.g.  the  vagus  or  the  pelvic  visceral  nerves.  The  three  systems  of 
ganglia  have  been  distinguished  as  the  lateral,  collateral,  and  terminal 
ganglia. 

The  ganglia  of  the  sympathetic  chain  are  connected  with  all  the 
spinal  nerves,  just  after  they  have  given  off  their  posterior  divisions, 
by  means  of  the  rami  communicantes.  These  rami  communicantes 
are  of  two  kinds  :  white  rami  consisting  of  small  medullated  fibres, 
and  grey  rami  composed  almost  exclusively  of  non-medullated  nerves. 
It  has  been  shown  by  Gaskell  that  the  white  rami  are  formed  by 
fibres  which  have  their  origin  in  the  spinal  cord  and  perhaps  in  the 
posterior  root  ganglia  ;  whereas  the  grey  rami  represent  fibres  which, 
arising  in  the  sympathetic  ganglia,  run  back  to  join  the  spinal  nerves. 
The  visceral  outflow  represented  by  the  white  rami  is  limited  to  a 
distinct  region  of  the  cord,  viz.  from  the  first  thoracic  to  the  third 
or  fourth  lumbar  nerve- roots  ;  whereas  the  grey  rami  pass  from  the 
sympathetic  to  all  the  spinal  nerve-roots.  It  is  found  by  experiment 
that  stimulation  of  a  limited  number  of  white  rami  produces  all  the 


THE  AUTONOMIC  NERVOUS  SYSTEM  523 

effects  that  can  be  evoked  by  stimulation  of  the  grey  rami,  showing 
that  the  impulses  ]ea\'ing  the  cord  pass  upwards  and  downwards 
in  the  sympathetic  system  and  are  broken  somewhere  in  their  course, 
being  transferred  to  a  fresh  relay  which,  by  means  of  non-nividullated 
nerves,  carries  them  on  to  their  destination. 

Finally,  in  certain  organs  of  the  body  are  to  be  found  sheets 
of  nerve  structures,  including  both  ganglion  cells  and  fibres,  which 
must  be  regarded  as  local  nerve-centres,  capable  of  carrying  out 
co-ordinated  acts  in  response  to  stimuli,  independently  of  the  central 
nervous  system.  It  seems  probable  that  these  systems  are  to  be 
regarded  as  analogous  rather  to  the  diffuse  neuro-fibrillar  system  of 
an  animal,  such  as  the  medusa,  than  to  the  synaptic  nervous  structures 
characteristic  of  the  central  nervous  system  of  vertebrates.  In  the 
latter  the  direction  and  effect  of  any  impulses  are  determined  by 
the  synapses  intervening  between  various  systems  of  neurons  and 
allowing  the  passage  of  the  impulse  only  in  one  direction.  This 
law  of  forward  direction  has  not  been  proved  to  hold  good  for  the 
primitive  nerve  systems ;  an  impulse  apparently  spreads  equally 
well  in  either  direction.  As  a  type  of  this  peripheral  diffuse  nerve 
system  may  be  cited  the  Auerbach's  and  Meissner's  plexuses  in  the 
wall  of  alimentary  canal.  How  far  we  are  to  regard  the  nerve-nets 
in  the  other  viscera,  such  as  the  heart  and  the  bladder,  as  conforming 
to  this  type  is  still  a  moot  point,  and  will  be  discussed  in  dealing  with 
the  origin  of  the  heart-beat. 

The  relationships  of  the  white  and  grey  rami  are  strikingly  illus- 
trated in  the  case  of  the  pilomotor  systems  of  nerves.  These  in  the 
cat  arise  from  the  cord  by  the  anterior  roots  from  the  fourth  thoracic 
to  the  third  lumbar  inclusive.  Passing  by  the  white  rami  to  the 
sympathetic  system,  they  travel  upwards  and  downwards  and  end 
by  arborisations  in  the  various  ganglia  of  the  main  chain.  From 
the  cells  of  each  ganglion  a  fresh  relay  of  fibres  starts,  which  runs 
as  a  bundle  of  non-raedullated  nerves  (the  grey  ramus)  to  the  corre- 
sponding spinal  nerve,  with  which  it  is  distributed  to  its  peripheral 
destination.  Each  grey  ramus  causes  erection  of  the  hairs  above 
one  vertebra,  whereas  stimulation  of  one  white  ramus  causes  erection 
over  three  or  four  vertebroe.  showing  a  distribution  of  the  fibres  of 
the  white  ramus  to  the  cells  in  several  successive  ganglia. 

These  pilomotor  fibres  in  the  cat  have  the  following  distribution  : 

(1)  For  the  head  and  upper  part  of-  the  neck  the  fibres  arise  by 
the  fourth  to  the  seventh  thoracic  anterior  roots,  and  have  their 
cell  stations  in  the  superior  cervical  ganglion.  They  travel  as  small 
meduUated  nerve  fibres  from  the  white  rami  up  the  sympathetic 
chain,  through  the  stellate  ganglion  and  ansa  Vieussenii  and  up  the 
cervical  sympathetic. 


524 


PHYSIOLOGY 


(2)  The  next  set  of  nerve  fibres  have  their  cell  station  in  the 
stellate  ganglion.  The  white  rami  arise  from  the  fifth  to  the  eighth 
thoracic  nerves,  while  the  grey  rami  pass  to  the  nerve-roots  from  the 
third  cervical  nerve  to  the  fourth  thoracic  nerve. 

(3)  The  remaining  nerves,  supplying  all  the  rest  of  the  body 
and  tail,  arise  by  the  white  rami  from  the  seventh  thoracic  to  the 


Posc'root 
AnL'  root 


Pre-ganglionic  fibre 


-  -Symp.  gangl. 


Made-up"  spinal  nerve  ' 


Post-ganglionic  fibre 


Fig.  237.  Diagram  (after  Langley)  to  show  the  manner  in  which  a  spinal  nerve  is 
completed  by  the  entry  of  a  grey  ramus,  containing  fibres  derived  from  cells  in 
the  sympathetic  chain. 

p.pr.d,  posterior  primaiy  division.       (The    post-ganglionic  fibres   are    repre- 
sented red.) 

third  or  fourth  lumbar  nerve,  and  are  distributed  as  grey  rami  to 
all  the  spinal  nerves  below  the  fourth  thoracic. 

We  thus  see  that,  in  speaking  of  the  functions  of  a  spinal  nerve- 
root,  we  must  clearly  distinguish  whether  we  mean  the  root  as  it 
arises  from  the  spinal  cord,  in  which  case  its  visceral  fvmctions  will 
include  those  of  its  white  ramus,  or  whether  we  mean  the  made-up 
or  complete  spinal  nerve  after  it  has  received  its  grey  ramus  (Fig.  237). 
In  the  latter  case  the  visceral  functions  of  the  root  will  be  more 
restricted  than  in  the  former  case,  and  will  have  a  different  distribu- 
tion. In  stimulating  the  nerve-roots  in  the  spinal  canal  it  is  sometimes 
possible,  by  weak  stimuli,  to  display  the  functions  of  the  corresponding 
white  ramus,  and  then  by  increasing  the  stimulus  to  get  superadded 
the  effects  due  to  the  excitation  of  the  grey  ramus  in  the  made-up 
nerve,  in  consequence  of  the  spread  of  current. 

"  When,  for  example,  the  eleventh  thoracic  anterior  roots  are  stimulated 
in  the  spinal  canal  with  weak  shocks,  a  fairly  long  strip  of  hairs  in  the  lumbar 


THE  AUTONOMIC  NERVOUS  SYSTEM  525 

region  will  be  erected,  the  maximum  movement  of  the  hairs  being  near  the 
middle  of  the  strip.  This  marks  the  area  of  distribution  of  the  pilomotor  nerves 
given  by  the  eleventh  thoracic  nerve  to  the  sympathetic.  If  then  the  strength 
of  the  shock  be  increased  to  a  certain  point,  the  hairs  in  the  long  strip  will  of 
course  be  erected  as  before,  but  in  addition  there  will  be  energetic  erection 
of  hairs  in  a  short  strip  a  little  distance  above  the  long  strip,  and  separated 
from  it  by  a  quiescent  region.  This  short  strip  is  the  same  as  that  affected 
by  stimvdating  the  grey  ramus  or  the  dorsal  cutaneous  branch  of  the  eleventh 
thoracic  nerve.  It  marks  the  area  of  distribution  of  the  pilomotor  fibres  received 
by  the  spinal  nerve  from  the  sympathetic  "  (Langley). 

We  may  now  indicate  briefly  the  main  course  and  functions  of 
the  fibres  of  the  sympathetic  system. 

(1)  The  head  and  neck  are  supplied  by  fibres  leaving  the  spinal 
cord  by  the  first  five  dorsal  nerves  (chiefly  by  the  second  and  third). 
They  all  have  their  cell  station  in  the  superior  cervical  ganglion. 
They  convey  : 

Vaso-constrictor  impulses  to  the  blood-vessels. 

Dilator  fibres  to  the  pupil. 

Secretory    (trophic  ?)    fibres    to    the    salivary    glands    and   sweat 

glands. 
Vaso-dilator  fibres  to  the  lower  lip  and  pharynx  (?). 

(2)  The  thoracic  viscera  (heart  and  lungs)  are  supplied  by  the 
same  five  nerve-roots.  The  cell  station  of  these  fibres  is,  however, 
situated  in  the  stellate  ganglion.     They  convey  : 

Accelerator  or  augmentor  impulses  to  the  heart. 

(3)  The  abdominal  viscera  receive  fibres  from  the  lower  six  dorsal 
nerves  and  the  upper  three  or  four  lumbar.  Most  of  these  fibres 
run  through  the  sympathetic  chain  without  making  any  connection 
with  tlie  ganglia,  and  have  their  cell  stations  in  the  collateral  ganglia 
of  the  solar  plexus,  the  semilunar  and  superior  mesenteric  ganglia. 
On  their  way  to  these  ganglia  they  form  the  gxeater  and  lesser 
splanchnic  nerves.     Their  functions  are  : 

Vaso-constrictor  for   stomach   and  small    intestine,    kidney,    and 

spleen. 
Probably  vaso-dilator  for  the  same  viscera. 

Inhibitory  for  both  muscular  coats  of  stomach  and  small  intestine. 
Motor  for  ileocolic  sphincter. 

(4)  The  pelvic  viscera  are  supplied  by  the  lower  dorsal  and  upper 
three  or  four  lumbar  nerve- roots.  These  fibres  also  pass  by  the 
main  chain  to  make  connections  with  tlie  cells  chiefly  in  the  inferior 
mesenteric  ganglia.     They  convey  : 

Vaso-constrictor  impulses  to  pelvic  viscera. 
Inhibitory  fibres  to  colon  (both  coafs). 
Motor  and  also  inhibitory  fibres  to  bladder. 
Motor  fibres  to  retractor  penis. 


526 


PHYSIOLOGY 


Motor  and  inhibitory  fibres  to  uterus  and  vagina. 

(5)  The  fore  limb  receives  nerves  from  the  white  rami  of  the 
fourth  to  the  tenth  thoracic  nerves.  All  these  fibres  are  connected 
with  cells  in  the  stellate  ganglion.     They  convey  : 

Vaso- constrictor  impulses  to  the  blood-vessels 
Secretory  nerves  to  the  sweat  glands. 

(6)  The  hind  limb  is  supplied  by  the  ner>*e-roots  from  the  eleventh 
thoracic  to  the  third  lumbar  inclusive.     The  cell  stations  of  these 


Spinal  cord 


) Sppathetic  chain 


t-^-n 


--  Solar  ganglion 


Fig.  238.     Figure  (after  Langley)  to  show  the  probable  mode  of  con- 
nection of  the  fibres  of  the  splanchnic  nerve  with  nerve-cells. 

A,  usual  type,  all  the  fibres  passing  through  the  lateral  chain 
to  end  in  the  collateral  ganglia  of  the  solar  plexus  ;  B,  alternative 
condition,  in  which  a  small  minority  of  the  fibres  have  their  cell- 
stations  in  the  sympathetic  chain.  The  pre -ganglionic  fibres  are 
black,  the  post-ganglionic  red. 


fibres  are  situated  in  the  sixth  and  seventh  lumbar  and  first  sacra) 
ganglia.     They  convey  : 

Vaso- constrictor  impulses. 

Secretory  nerves  to  the  sweat  glands. 

Every  fibre  of  the  sympathetic  system  is  thus  in  some  point  of 
its  course  interrupted  by  a  nerve-cell,  and  Langley  has  shown  that 
this  is  the  only  cell-break  in  the  fibre,  i.e.  every  fibre  is  connected 
with  one  cell  and  one  cell  only.  This  law  applies  not  only  to  the 
sympathetic  fibres  but  also  to  the  fibres  of  the  other  visceral  nerves. 
Each  fibre  therefore  can  be  regarded  as  made  up  of  two  sections — 
a  pre- ganglionic  fibre  arising  in  the  central  nervous  system  and  passing 
down  to  a  ganglion  as  a  fine  medullated  nerve  fibre,  and  a  post- 


THE  AUTONOMIC  NERVOUS  SYSTEM  527 

ganglionic   fibre   arising   in    this   ganglion    and   continued   generally 
as  a  non-medullated  fibre  to  its  peripheral  distribution. 

This  transference  from  one  system  to  another  involves  the  passage 
across  a  synapse  and  a  nerve-cell.  The  situation  of  this  nerve-cell 
may  be  easily  revealed  by  utilising  the  action  of  nicotine,  first  studied 
by  Langlev.  If  nicotine  be  apphed  to  a  sympathetic  gangUon,  it 
first  stimulates  and  then  paralyses  any  junction  between  axon  ter- 
mination and  nerve-cell  which  may  lie  in  the  ganglion.  Intravenous 
injection  of  nicotine  therefore  causes  a  primary  general  excitation 
of  all  visceral  gangUon-cells.  There  is  an  enormous  rise  of  blood 
pressure,  which  may  be  accompanied  by  other  sympathetic  effects, 
such  as  dilatation  of  the  pupil,  secretion  of  saliva,  erection  of  the 
hairs,  and  so  on.  This  rise  rapidly  passes  off,  and  it  is  then  found 
impossible  to  evoke  an}''  reflex  visceral  effects  or  any  contraction, 
e.g.  of  the  blood-vessels,  by  stimulatioii  of  the  spinal  cord ;  the  passage 
of  the  impulses  is  blocked  in  every  one  of  the  \asceral  ganglia.  By 
observing  the  effects  of  stimulation  of  a  nerve  before  it  enters  a 
ganglion  and  then  painting  the  ganglion  with  nicotine  and  again 
trying  the  effects  of  excitation,  it  is  easy  to  determine  whether  the 
nerve  fibres  which  were  excited  in  the  first  case  form  any  connections 
with  the  nerve-cells  of  the  ganglion.  In  the  strength  in  which  it  is 
usually  applied  nicotine  is  without  effect  on  nerve  fibres. 

THE  CRANIAL   AUTONOMIC  FIBRES 

In  the  course  of  development  the  greater  part  of  the  fibres  of 
the  facial  nerve  have  lost  their  special  visceral  functions  and  have 
the  aspect  and  functions  of  ordinary  somatic  fibres.  Visceral  fibres 
are  contained  in  the  following  cranial  nerves — the  third,  seventh, 
ninth,  tenth,  and  eleventh. 

Third  nerve.  The  visceral  fibres  of  this  nerve  pass  to  the  ciliary 
ganglion  in  the  orbit  where  they  end  ;  the  post- ganglionic  fibres 
from  this  gangUon  form  the  short  ciliary  nerves  which  innervate  the 
sphincter  pupillse  and  the  ciliary  muscles. 

Seventh  nerve.  The  autonomic  fibres  of  the  facial  arise  from  the 
medulla  in  the  intermediate  nerve  of  Wrisberg,  which  is  practical!}- 
the  anterior  continuation  of  the  ninth,  tenth,  and  eleventh  nerves. 
From  the  seventh  nerve  is  derived  the  chorda  tympani  nerve,  which 
supplies  vaso-dilator  nerves  to  the  tongue,  the  submaxillary  and 
sublingual  glands,  and  secretory  fibres  to  these  glands. 

The  cell  stations  of  these  nerves  lie  peripherally,  those  of  the 
sublingual  gland  in  the  so-called  submaxillary  ganglion  ;  those  of 
the  submaxillary  gland  in  the  hilus  of  this  organ.  It  is  probable 
that  the  seventh  sends  also  pre- ganglionic  visceral  fibres  to  the  spheno- 
palatine ganglion,  whence  a  fresh  relay  of  fibres — post-ganglionic — 


528  PHYSIOLOGY 

run  with  the  branches  of  the  fifth  nerve,  to  supply  secretory  fibres 
and  possibly  vaso- dilator  fibres  to  the  mucous  membrane  of  the  nose, 
soft  palate,  and  upper  part  of  the  pharynx.  The  glossopharyngeal 
or  ninth  nerve  sends  fibres,  which  evoke  secretion  as  well  as  vaso- 
dilatation in  the  parotid  gland,  via  the  otic  ganglion.  Probably  also 
dilator  fibres  leave  this  nerve  to  supply  vessels  at  the  back  of  the 
tong-ue. 

THE  VAGUS 
The  efferent  visceral  fibres  of  the  tenth  and  eleventh  nerves  arise 
in  the  same  column  of  cells  as  the  two  nerves  just  considered.  Most 
of  the  fibres  run  in  the  vagus.  They  include  motor  fibres  to  the 
oesophag-us,  stomach,  and  small  intestines  as  far  as  the  ileocolic 
sphincter  ;  inhibitory  fibres  to  the  heart,  motor  fibres  to  the  un- 
striated  muscles  of  the  bronchi,  and  secretory  fibres  to  the  gastric 
glands.  The  cell  stations  of  these  fibres  are  apparently  situated 
peripherallv,  the  jugular  ganglion,  and  the  ganglion  of  the  trunk 
of  the  vagus  being  in  all  likelihood  responsible  only  for  the  afferent 
fibres  in  this  nerve.  Nicotine  therefore  abohshes  any  effect  of  stimu- 
lating the  vagus  in  the  neck,  though  inhibition  of  the  heart  can  still 
be  produced  on  excitation  of  the  post- ganglionic  fibres  arising  from 
the  cells  in  the  sinus  venosus. 

SACRAL   AUTONOMIC  FIBRES 

These  all  run  in  the  peh-ic  visceral  nerve,  also  called  nervus 
ericjens.  This  nerve  is  connected  with  a  collection  bi  ganglia  lying, 
in  the  hypogastric  plexus  at  the  base  of  the  bladder.  It  has  the 
follo-sving  functions  : 

Dilator  to  vessels  of  the  penis  (hence  its  name  of  nervus  erigens). 

Motor  to  bladder,  colon,  and  rectum. 

Inhibitory  to  sphincter  muscle  of  bladder. 

Inhibitory  to  retractor  penis. 

It  will  be  observed  that  in  many  cases  the  viscera  get  their  nerve 
supply  from  both  sets  of  visceral  nerves,  and  that  in  such  cases  the 
two  sets  of  nerves  are  antagonistic  in  function.  It  is  impossible, 
however,  to  draw  a  sharp  line  between  the  functions  of  the  two  sets, 
since  the  same  nerve  may  be  motor  for  one  set  of  muscular  fibres 
and  inhibitory  for  another  set  in  the  same  viscus.  Thus  the  colonic 
branches  of  the  inferior  mesenteric  ganglion  are  motor  (constrictor) 
for  the  blood-vessels  and  inhibitory  for  the  muscular  walls  of  the 
colon.  While  the  sympathetic  nerve-supply  is  inhibitory  for  nearly  the 
whole  intestinal  muscles,  it  produces  strong  contraction  of  the  band 
of  muscle  forming  the  ileocolic  sphincter.  In  the  bladder  there  is 
no  doubt  that  the  sympathetic  supply  includes  both  inhibitory  and 


THE  AUTONOMIC  NERVOUS  SYSTEM  520 

motor  fibres,  tlic  predominating  efEect  on  excitation  of  the  nerve  vary- 
ing from  one  species  of  animal  to  another. 

FUNCTIONS  OF  THE  SYMPATHETIC   AND  PERIPHERAL 
GANGLIA 

These  ganglia  consist  of  a  mass  of  nerve-cells  embedded  in  con- 
nective tissue,  each  cell  being  surrounded  by  a  special  capsule  of 
endothelial  cells.  The  nerve-cells,  though  in  section  resembling  those 
in  a  posterior  root  ganglion,  differ  from  these  in  being  multipolar,  each 
cell  probably  possessing  one  axon  and  several  dendrites.  The  den- 
drites end  in  little  arborisations  round  adjacent  cells. 

Since  the  main  nervous  system  is  characterised  by  the  possession 
of  nerve-cells,  it  was  formerly  thought  that  any  collection  of  nerve- 
cells  must  partake  of  the  co-ordinating  and  reflex  functions  of  the 
central  nervous  system,  i.e.  must  act  as  local  nervous  centres.  All 
efEeorts  have  failed,  however,  to  prove  the  existence  of  such  a  function, 
and  we  must  conclude  that  the  sole  use  of  these  ganglia  is_tq_serve 
as  distributing-centres.  We  may  assume  that  "one  pre -ganglionic  fibre 
divides,  and  the  branches  arborise  round  several  cells  (Fig.  238), 
whence  new  fibres  arise  to  carry  the  impulse  to  the  periphery — an 
impulse  in  the  case  of  which  there  is  no  need  for  any  minute  localisation. 
Indeed  the  essential  part  of  a  nerve-centre  is  not  the  nerve-cells  at  all, 
but  the  presence  of  a  complex  tangle  of  fibres,  rendering  possible 
the  passage  of  impulses  in  all  directions,  the  passage  of  an  indi\ndual 
impulse  being  limited  by  reason  of  the  varying  strength  of  the  impulse 
and  the  varying  resistance  of  the  many  possible  tracts.  In  many 
invertebrata  the  nervous  system  consists  of  a  punctated  material 
composed  of  a  dense  interlacement  of  fibrils,  while  tlie  cells  lie  outside 
the  centres  and  have  one  thick  process  dipping  into  the  nervous  mass, 
from  which  process  both  axon  and  dendrites  arise.  In  this  case,  as 
we  have  seen,  extirpation  of  the  cell  bodies  does  not  destroy  the 
capacity  of  the  remaining  fibrillar  substance  to  act  as  a  reflex  centre. 
Such  a  complex  of  fibres  is  found  in  mammals  in  the  plexuses  of  Auer- 
bach  and  Meissner,  which  act  as  local  nerve-centres  for  the  intestine. 
But  all  such  mechanism  is  wanting  in  the  sympathetic  ganglia,  which 
contain  neither  association  fibres  between  different  cells  of  a  ganglion 
nor  commissural  fibres  between  the  cells  of  adjacent  ganglia.  All  the 
fibres  in  a  sympathetic  ganglion  have  either  entered  it  from  the  white 
rami  or  are  destined  to  leave  it  as  fibres  of  grey  rami. 

Several  reflexes  formerly  described  in  jieripheral  ganglia,  as,  r../. 
the  'submaxillary'  ganglion,  have  been  proved  to  bo  fallacious. 
There  is,  however,  a  certain  group  of  phenomena  which  can  bo  elicited 
in  sympathetic  ganglia,  and  which  have  been  termed  by  Langley  and 
Anderson  pseudo-reflexes,  or,  better,  axon  reflexes.     If,  for  instance,  we 

34 


530  PHYSIOLOGY 

divide  all  the  nerves  going  to  the  inferior  mesenteric  ganglion,  leaving 
the  bladder  connected  with  the  inferior  mesenteric  ganglion  only 
by  the  hypogastric  nerves,  and  then  after  dividing  the  left  nerve 
.stimulate  its  central  end,  we  obtain  a  contraction  of  the  right  half 
of  the  bladder.  This  efEect  is  abolished  by  painting  the  inferior 
mesenteric  ganglion  with  nicotine,  showing  that  the  activity  of  the  cells 
of  this  ganglion  is  involved  in  the  process.  It  has  been  shown,  however, 
by  Langley  and  Anderson  that  this  is  not  a  true  reflex,  but  is  rather 

Sp.cord 


Inf.  mes.  g  --f 
Post -ganglionic  fibre 


Pre -ganglionic  fibre 
Hypogastric  nerves 


Fia.  239.     Diagram  to  illustrate  Langley  and  Anderson's  explanation  of  the  hypo- 
gastric reflex  as  an  axon  reflex. 
The  division  of  the  axon  where  the  propagation  or  '  reflexion  '  takes  place  is  at  X, 

analogous  to  Kiihne's  gracilis  experiment  {cf.  p.  285).  A  pre-ganglionic 
fibre  arriving  at  the  inferior  mesenteric  ganglion  branches,  one  branch 
ending  round  the  cells  of  the  ganglion,  while  the  other  branch  passes 
down  in  the  left  hypogastric  nerve  to  a  cell  situated  near  the  base  of 
the  bladder  (Fig.  239).  When  therefore  we  stimulate  this  nerve  we 
are  stimulating  a  pre-ganglionic  fibre,  and  the  excitation  spreads  up 
to  the  point  of  junction  of  the  two  branches  and  then  down  the  other 
branch  to  excite  the  cell  in  the  inferior  mesenteric  ganglion.  We  thus 
obtain  an  apparent  motor  reflex  by  stimulation  of  a  nerve  which  is 
itself 'motor.  Similar  pseudo-reflexes  can  be  obtained  along  the  abdo- 
minal chain  on  the  pilomotor  nerves,  but  furnish  no  grounds  for 
ascribing  the  property  of  reflex  centres  to  peripheral  ganglia.  On  the 
other  hand,  these  axon  reflexes  are  very  similar  to  the  spread  of  the 
excitatory  process  which  occurs  in  the  diffuse  nerve  network  of  an 
animal  such  as  the  medusa.  Irreciprocity  of  conduction  would  seem 
therefore  to  be  the  most  useful  criterion  of  a  true  reflex. 


THE  AUTONOMIC  NEK  VOL'S  SYSTEM  53i 

INHIBITION  IN  PERIPHERAL  GANGLIA 
The  existence  of  ganglion-cells  in  tlie  course  of  the  nerves  to 
visceral  muscles  has  often  been  supposed  to  account  for  certain 
peculiarities  in  the  innervation  of  visceral,  as  compared  with  skeletal, 
muscle.  Chief  among  the  differences  between  these  two  kinds  of 
muscle  is  the  frequency  with  which  inhibition  may  be  brought  about 
in  the  latter  by  stimulation  of  peripheral  efferent  nerves.  In  skeletal 
muscle  inhibition  is  only  known  as  the  result  of  alteration  of  the 
activity  of  the  motor  centres  from  which  it  is  supplied.  It  has 
therefore  been  thought  that  the  peripheral  ganglia  of  visceral  muscle 
play  the  part  of  the  motor  spinal  centres  of  skeletal  muscle,  and 
that  when  we  excite  an  inhibitory  nerve,  say  to  the  intestine, 
we  are  interfering  with  and  diminishing  a  tonic  state  of  activity 
which  has  its  seat  in  a  peripheral  ganglion-cell  connected  with  the 
visceral  muscle. 

This  view,  which  was  first  put  forward  by  Claude  Bernard,  has 
been  specially  defended  by  Dastre  and  Morat.  These  observers  point 
out  that  vaso-dilator  action  diminishes  or  disappears  as  nerve-strands 
are  stimulated  more  and  more  peripherally,  and  conclude  that  the 
vaso-dilator  fibres  run  to  the  sympathetic  ganglion  and  inhibit  their 
tonic  action.  The  untenability  of  this  view  has  been  demonstrated 
by  Langley.  Thus  the  chorda  tympani  fibres  run  to  a  local  nerve- 
'  centre  '  in  the  hilum  of  the  submaxillary  gland.  On  Bernard's 
theory  stimulation  of  the  fibres  peripherally  to  the  centre  should  cause 
contraction  of  the  arteries  ;  but  it  is  found  that,  after  paralysis  of  the 
ganglion  by  nicotine,  stimulation  of  the  post-ganglionic  fibres  causes 
dilatation,  so  that  the  nerve  fibres  given  off  from  the  local  centre  are 
not  vaso-constrictor  but  vaso-dilator.  Moreover  it  can  be  shown  that 
the  sympathetic  fibres  which  do  cause  constriction  make  no  connec- 
tion with  the  cells  in  the  hilum  of  the  gland,  but  run  on  the  walls  of  the 
arteries  to  their  distribution.  These  fibres  are  connected,  not  with 
cells  of  the  submaxillary  ganglion  (the  local  nerve-centre),  but  with 
cells  in  the  superior  cervical  ganglion. 

We  must  conclude  that  the  inhibitory  nerves  in  these  visceral 
structures  exert  their  influence  directly  on  the  peripheral  tissue,  and 
not  by  a  diminution  of  activity  of  a  tonically  acting  peripheral  centre, 

AFFERENT  FIBRES  AND  THE  AUTONOMIC  SYSTEM 
(Referred  Pain) 
The  supply  of  afferent  fibres  to  the  viscera  is  very  small  in  propor- 
tion to  the  supply  to  the  outer  surfaces  of  the  body.     According  to 
Langley,  in  a  visceral  nerve,  such  as  the  hypogastric,  only  about  one- 
tenth  of  the  medullated  fibres  are  afferent,  and  the  proportion  of 


532  PHYSIOLOGY 

afEerent  fibres  in  the  splanchnic  nerves  is  probably  not  very  difEerent 
from  this.  At  the  two  ends  of  the  alimentary  canal,  i.e.  at  the  mouth 
and  anus,  the  afferent  visceral  fibres  become  of  more  importance,  since 
through  their  means  co-operative  somatic  reflexes  have  to  be  excited 
as  well  as  the  simple  visceral  rej&exes.  Thus  in  the  pelvic  visceral 
nerve  about  one-third  of  the  fibres  are  afferent,  and  the  vagi  contain 
a  large  number  of  afferent  fibres  from  the  lungs  as  well  as  from  the 
other  viscera  innervated  by  it. 

According  to  Dogiel,  afferent  visceral  fibres  arise  from  sensory  cells  of  the 
sympathetic  ganglia  and,  passing  in  to  the  posterior  spinal  gangha,  divide  and 
form  pericellular  endings  round  a  special  iy\)^  of  posterior  root-cells,  the  axon 
from  which  divides  again  into  a  number  of  branches  which  end  in  connection 
with  tjTiical  unipolar  cells.  Thus,  according  to  this  observer,  a  few  afferent 
sympathetic  fibres  can  stimulate  a  considerable  number  of  posterior  root-cells. 
Langley,  however,  has  not  been  able  to  obtain  any  experimental  confirmation 
of  the  origin  of  branching  afferent  fibres  from  cells  of  the  sjTnpathetic  system. 

It  is  probable  that  the  afferent  fibres  of  the  visceral  nerves  arise,  like 

those  of  the  somatic  systemj  from  ganglion-cells  of  the  posterior  spinal 

ganglia.     Every  white  ramus  contains  afferent  fibres,  stimulation  of 

which  may  evoke  a  rise  of  blood  pressure  as  well  as  movements  of  the 

skeletal  muscles.     In  spite  of  the  supply  of  afferent  fibres  to  the  viscera, 

most  of  these  organs  are  very  insensitive  to  ordinary  stimulation  such 

as  handling  or  cutting.     In  operations  on  man  for  resection  of  the  gut, 

if  the  abdominal  cavity  be  opened  under  local  or  general  anaesthesia, 

cutting  and  suturing  may  be  conducted  without  any  anaesthetic  and 

without  causing  any  pain  to  the  patient.   On  the  other  hand,  impulses 

may  arise  in  the  afferent  nerve-endings  of  the  viscera,  as  a  result  of 

disease  or  certain  forms  of  stimulation,  e.g.  stretching  or  compression, 

which  may  reach  consciousness  and  give  rise  to  the  sensation  of  pain. 

This  pain  is  not,  however,  localised  in  the  viscera,  but  is  referred  to 

certain  parts  of  the  surface  of  the  body.  "When  the  afferent  autonomic 

fibres  of  a  nerve  are  the  seat  of  pain,  the  primary  referred  pain  is  in 

the  area  of  the  cutaneous  somatic  fibres  of  the  n6rve.    It  has  been 

shown  by  Mackenzie  and  by  Head  that  visceral  disease  may  cause 

hyper-sensitivity  of  the  corresponding  areas  of  the  skin,  and  a  method 

has  been  elaborated  by  these  observers  for  utilising  this  referred  pain 

or  skin  tenderness  as  a  means  of  localising  the  site  of  the  disease. 


CHAPTER  VIII 
THE  PHYSIOLOGY  OF  SENSATION 

SECTION  I 

ON  THE  RELATION  OF  SENSATION  TO  STIMULUS 

Up  to  the  present  we  have  dealt  with  the  central  nervous  system 
as  a  machine  for  the  conversion  of  afferent  into  appropriate  efferent 
impulses,  and  have  regarded  the  sense-organs  simply  as  mechanisms 
by  means  of  which  stimuli  of  various  quality,  arising  from  events  in 
the  environment  of  the  animal,  could  give  rise  to  nerve  impulses.  We 
have  seen  reason  to  assign  these  afferent  impressions  to  various  classes, 
according  to  the  physical  character  of  the  stimulus  involved  and 
according  to  the  quality  of  the  response.  The  nature  of  the  physio- 
logical processes  evoked  in  the  organism  depends  on  the  physical 
nature  of  the  stimulus  and  the  locus  of  its  incidence  on  the  surface  of 
the  body.  Thus  a  nocuous  stimulus  applied  to  the  foot  causes  flexion 
of  the  leg,  whereas  steady  pressure  on  the  sole  evokes  a  '  stepping ' 
reflex  with  extension  of  the  leg.  A  beam  of  light  falling  on  the  eye 
calls  forth  movements  involving  contractions  of  the  intrinsic  and 
extrinsic  ocular  muscles.  The  same  beam  of  light  falling  on  the  skin 
is  devoid  of  effect  unless  it  is  so  strong  as  to  burn  the  skin,  when  a 
reflex  is  excited  similar  to  that  evoked  by  a  nocuous  stimuhis.  As 
our  study  of  the  adaptive  nerve  mechanisms  becomes  more  detailed, 
and  especially  when  we  take  into  account  the  activities  of  the  asso- 
ciation centres  in  the  cortex,  it  becomes  more  and  more  difficult  to 
follow  the  chain  of  processes  which  lead  to  any  given  reaction  ;  in 
order  to  advance  further  in  our  knowledge  of  the  activity  of  the 
receptor  organs,  we  have  frankly  to  abandon  the  objective  method 
which  has  served  us  in  the  study  of  all  the  other  functions  of  the 
body,  and  appeal  to  our  own  consciousness  for  information  as  to  the 
effects  of  their  excitation.  Each  one  of  us  is  aware  that  stinndation 
of  an  afferent  nerve  may  cause  a  change  in  consciousness  which  we 
denote  as  a  sensation,  and  we  attribute  to  other  living  organisms, 
presenting  similar  reactions  to  ourselves,  similar  changes  in  conscious- 
ness in  consequence  of  like  stinudi. 

Certain  sensations  differ  one  from  the  other  to  such  an  extent  ihat 

533 


534  PHYSIOLOGY 

comparison  among  them  becomes  impossible.  Thus  in  the  skin  and 
underlying  parts  we  have,  as  a  result  of  stimulation,  sensations  of 
touch  and  pressure,  sensatiqns  of  heat  and  of  cold,  and  sensations  of 
pain.  The  contact  of  certain  dissolved  substances  with  the  end-organs 
of  the  gustatory  nerves  excites  in  us  a  sensation  of  taste.  Other  sub- 
stances diffused  in  the  air  and  carried  by  it  to  the  olfactory  termina- 
tions give  us  sensations  of  smell.  Vibrations  of  a  certain  frequency, 
transmitted  by  the  air  and  by  the  auditory  ossicles  to  the  endings  of 
the  auditory  nerve,  produce  sensations  of  sound,  while  light  falling 
on  the  retina  evokes  visual  sensations. 

Besides  these  sensations  resulting  from  stimulation  of  the  extero- 
ceptive system  of  nerves,  we  are  aware  of  the  existence  of  a  number  of 
organic  sensations — some  derived  from  the  viscera  (enteroceptive), 
others  caused  by  stimulation  of  the  proprioceptive  system.  As 
examples  of  the  latter  we  may  mention  the  muscular  sense,  by  which 
we  judge  of  the  amount  of  tension  exerted  by  a  contracting  muscle  ; 
the  sense  of  position  of  the  limbs  ;  and  the  sense  of  position  of  the  head, 
resulting  from  stimulation  of  the  labyrinthine  organ. 

How  the  physiological  excitatory  process  in  nerve  fibres,  with 
its  concomitant  chemical  and  electrical  phenomena,  is  able  on  arrival 
at  the  brain  to  excite  a  conscious  sensation  we  are  unable  to  decide,  or 
even  to  discuss,  since  we  are  dealing  here  with  processes  of  two  different 
orders.  We  should  not  arrive  any  nearer  to  the  solution  of  this 
riddle  if  we  were  able  to  follow  out  the  whole  of  the  events  occurring 
in  the  body  as  the  result  of  the  appUcation  of  any  given  stimulus  to  its 
surface.  We  might  under  these  circumstances  be  able  to  predict  with 
certainty  the  behaviour  of  any  animal,  if  we  knew  its  past  history 
and  the  comparative  resistance  of  every  path  m  its  central  nervous 
system  which  might  possibly  be  traversed  by  any  given  nerve  impulse. 
Such  knowledge  would  be  purely  objective  and  could  not  he  used  to 
explain  the  '  epi-phenomenon  '  of  consciousness.  One  might  in 
fact  imagine  a  machine  which  would  react  like  a  living  animal,  but 
would  be  perfectly  devoid  of  self-consciousness,  and  we  should  be 
unable  in  such  a  case  to  decide  whether  consciousness  were  or  were 
not  present.  Each  one  of  us  only  knows  consciousness  as  it  exists  in 
himself. 

Before  therefore  we  can  employ  our  conscious  sensations  as  a 
means  of  throwing  light  on  the  conditions  of  action  of  the  receptor 
organs  of  the  body,  we  must  have  some  idea  as  to  how  far  our  sensa- 
tions correspond  to  the  stimuli,  i.e.  the  phy Laical  events  by  which 
they  have  been  evoked.  Appeal  to  our  own  experience  shows  the 
existence  of  two  kinds  of  difference  between  various  sensations. 
The  greatest  difference  is  found  between  those  sensations  which 
are  normally  evoked  by  different  sense-organs.      Thus  we  are  all 


RELATION  OF  SENSATION  TO  STIMULUS  535 

aware  of  the  meaning  attached  to  such  qualities  or  such  sensations 
as  sweet,  red,  hard,  high-pitched  (of  sound),  &c.  It  would  be  abso- 
lutely impossible  to  compare  these  sensations  among  themselves. 
We  cannot  say,  for  instance,  that  this  sound  is  louder  than  that 
colour  is  red.  Such  fundamental  differing  quahties  of  sense  are 
spoken  of  as  the  modality  of  the  sensation. 

On  the  other  hand,  within  the  sensation  evoked  by  any  one  sense- 
organ  we  find  differences  of  quality  which  are  more  comparable 
among  themselves.  Thus  we  can  compare  the  pitch  of  various 
soundS;  or  the  colour  of  various  objects  seen  with  the  eye.  We 
can  even  say  that  the  bitter  taste  of  any  substance  is  more  marked 
than  the  sweet  taste  of  another.  The  question  arises  how  far  these 
differences  in  sensation  correspond  to  and  are  a  measure  ot  differences 
in  the  physical  events  by  which  they  have  been  evoked.  A  very  little 
consideration  suffices  to  show  that  there  is  no  resemblance  between 
a  sensation  and  the  stimulus,  and  that  one  and  the  same  physical 
event  appUed  to  different  sense-organs  will  evoke  absolutely  distinct 
sensations ;  while  difierent  modes  of  stimuh  apphed  to  one  sense- 
organ  will  always  evoke  the  same  sensation.  Thus  if  hght  falls 
on  the  retina  it  causes  a  sensation  of  light.  If  the  same  radiant 
energy,  consisting  of  transverse  vibrations  in  the  ether,  be  allowed 
to  fall  on  the  skin,  it  either  produces  no  sensation  at  all,  or,  if  con- 
centrated by  means  of  a  burning-glass,  may  give  rise  to  a  sensation 
of  warmth,  heat,  or  pain.  If  we  take  a  tuning-fork  which  is  vibrating 
100  times  per  second  and  apply  it  to  the  surface  of  the  skin,  we  get 
simply  a  sensation  of  vibration,  i.e.  a  series  of  tactile  impressions 
repeated  at  rapid  intervals.  If  the  same  tuning-fork  be  apphed  to 
the  head,  its  vibrations  are  imparted  to  the  bones  of  the  sknill  and 
thence  to  the  auditory  nerve-endings  and  arouse  in  our  consciousness 
a  tone-sensation  of  a  certain  note.  The  same  thing  happens  if  the 
vibrations  of  the  tuning-fork  are  conducted  by  the  ear  to  the  auditory 
nerve-endings  in  the  ordinary  way  through  the  external  and  middle 
ear.  On  the  other  hand,  a  sensation  of  light  may  be  aroused  not  only 
by  the  incidence  of  radiant  energy  of  a  certain  wave  length  on  the 
retina,  but  also  by  electrical  or  mechanical  stimulation  of  the  retina. 
If  the  eye  be  turned  inwards  and  the  finger  be  pressed  on  the  eye 
through  the  outer  canthus  of  the  Uds,  a  sensation  of  light  is  aroused 
and  we  see  a  coloured  circle  which  we  refer  to  some  spot  lying  to  the 
nasal  side  of  the  eye  stimulated.  The  character  of  the  sensation  bears 
therefore  no  resemblance  to  the  physical  events  by  which  the  sensation 
is  evoked,  but  depends  entirely  on  the  nature  of  the  sense-organ  which 
is  stimulated.  A  sensation  of  light  may  be  produced  by  stimulation 
in  any  way  of  the  retina,  or  of  the  optic  nerve,  or  of  the  terminations  of 
the  optic  nerve  in  the  brain.     In  the  same  way  stimulation  of  an 


536  PHYSIOLOGY 

auditory  nerve  or  its  intracranial  endings  gives  rise  to  sensations 
of  sound. 

Where  the  question  has  been  investigated  it  has  not  been  found 
possible  to  evoke  different  qualities  of  sensation  by  different  modes 
of  stimulation  of  nerve  fibres,  and  it  has  therefore  been  concluded  that 
the  quahty  of  any  sensation  depends  simply  and  solely  on  the  termina- 
tion of  these  nerves  in  the  central  nervous  system,  and  that  where 
sensations  of  difierent  quality  are  produced  there  must  be  also  difference 
of  nerve  fibres.  This  idea  was  formulated  by  Miiller,  and  is  often 
alluded  to  as  Miiller's  '  law  of  specific  irritability.'  The  law  states 
that  every  sensory  nerve  reacts  to  one  form  of  stimulus  and  gives  rise 
to  one  form  of  sensation  only,  though  if  under  abnormal  conditions  it 
be  excited  by  other  forms  of  stimuh,  the  sensation  evoked  will  be  the 
same. 

Although  the  different  forms  of  sensation  must  be  regarded 
as  dependent  on  the  integrity  of  the  brain,  and  of  its  connections 
with  the  peripheral  sense-organs,  sensations  are  not  referred  to  the 
brain,  but  are  localised  as  proceeding  from  some  part  of  the  body 
or  from  some  region  outside  of  the  body.  Thus  the  sensation  of 
taste  is  always  localised  in  the  mouth  ;  sensation  of  touch  at  the 
skin  or  surface  of  the  body ;  while  the  sensations  of  hearing  and  of 
sight  are  '  projected,'  i.e.  are  interpreted  as  coming  from  the  environ- 
ment outside  ourselves.  Even  the  organic  sensations  of  posture  or 
fatigue  are  referred  to  the  peripheral  reacting  parts  of  the  body  and 
not  to  the  central  nervous  system.  A  sensation  therefore  cannot  be 
interpreted  as  a  reproduction  of  external  events,  but  as  a  symbol  of 
these  events  evoked  by  stimulation  of  the  sense-organs  of  the  body. 

It  is  indeed  impossible  by  a  pm-ely  mtuitive  study  of  sensations 
to  arrive  at  any  correct  idea  of  their  origin  or  of  the  factors  concerned 
in  their  production.  No  sensation  is  the  immediate  and  sole  product 
of  a  stimulus  applied  to  the  peripheral  end  of  a  nerve  fibre,  but  the 
simplest  sensation  involves  a  judgment,  i.e.  complex  neural  activities 
which  are  the  resultant  of  innumerable  past  and  present  streams  of 
nervous  impulses  aroused  by  peripheral  events  and  pomed  into  the 
central  nervous  system.  It  is  important  therefore  not  to  regard  a 
sensation  as  in  any  way  constituting  an  elementary  unit,  by  the 
aggregation  of  a  number  of  which  a  conscious  state  is  produced.  As 
we  have  seen,  the  primitive  function  of  the  whole  nervous  system  is 
reaction.  The  neural  Ufe  of  an  animal  is  composed  of  a  series  of  reac- 
tions, some  simple,  some  complex,  and  becoming  ever  more  compli- 
cated as  we  ascend  the  animal  scale.  The  first  reactions  of  a  baby, 
for  instance,  will  be  those  by  which  it  procures  nourishment  and  satisfies 
a  need.  The  earliest  event  in  its  dawnina;  consciousness  will  be, 
not  a  sensation  of  sweetness  or  of  colour,  but  that  of  a  thing  which  can 


RELATION  OF  SENSATION  TO  STIMULUS  537 

satisfy  its  needs.  It  will  have  had  to  try  many  gustatory  experiments 
before,  out  of  the  sum  of  its  material  experiences,  it  will  be  able  to 
choose  a  number  of  like  factors  which  can  be  grouped  together  as 
'  sweet.'  Judgment  of  quality  of  sensation  involves  a  power  of 
abstraction  and  of  classifying  similar  elements  in  different  nem-al  events 
or  reactions  and  the  referring  of  these  elements  to  the  external  world. 
It  is  very  difficult,  however,  to  divest  ourselves  of  the  mental  stand- 
point reached  as  the  result  of  many  years'  continual  trials,  successes 
and  failures,  and  constant  care  has  to  be  exercised  if  we  are  not  to 
fall  mto  the  common  conception  of  the  ego,  the  personality,  or  soul, 
as  a  sort  of  sentient  god  sitting  somewhere  in  the  brain,  or,  as  Descartes 
suggested,  in  the  pineal  gland,  and  receiving  by  means  of  one  part  or 
other  of  his  servile  material  brain  a  blue  sensation  from  the  eyes, 
or  an  auditory  impression,  or  a  tactile  impression,  and  then,  if  he  feels 
so  inclined,  pressing  the  stop  in  a  pyramidal  cell  to  let  out  a  voluntary 
motor  response.  An  elementary  unit  in  psychical  life,  as  in  neiural 
life,  must  be  a  complete  reaction.  It  is  from  the  reaction  and  not  from 
the  sensation  that  a  constructive  psychology  will  have  to  be  built  up. 

Although  an}^  given  sensation  may  be  produced  by  many  forms  of 
stimulation  of  the  sense-organ,  under  normal  circumstances  each 
sense-organ  is  so  arranged  and  protected  that  it  is  only  stimulated 
by  one  kind  of  physical  process,  i.e.  by  the  one  for  which  its  liminal 
or  threshold  excitability  is  at  a  minimum.  Thus  the  retina,  though 
it  may  be  stimulated  mechanically  or  electrically,  is  in  the  normal 
individual  very  thoroughly  protected  from  the  possibihty  of  such 
excitation,  so  that  all  impulses  arising  in  the  retina  may  be  almost 
certainly  referred  to  changes  in  the  light- waves  which  fall  on  the 
eye,  and  by  means  of  the  dioptric  mechanism  of  this  organ  are  thrown 
in  a  distinct  pattern  upon  the  retina.  Although  the  sensation  is  not 
a  reproduction  of  the  stimulus,  it  is  a  symbol  of  the  stimulus,  and 
can  be  used  to  inform  us  of  events  occurring  in  the  world  around. 
Like  stimuli,  falling  on  the  same  end-organ,  always  evoke  like  sensa- 
tions, other  conditions  being  equal.  An  orderly  sequence  of  sensa- 
tions may  therefore  be  interpreted  as  indicating  a  corresponding 
orderly  sequence  of  physical  occurrence  in  the  world  around  us. 

THE  QUANTITATIVE  RELATIONSHIPS  BETWEEN  STIMULUS 
AND  SENSATION 
Since  our  sensations  are  merely  symbols  of  the  physical  conditions 
which  give  rise  to  them,  it  is  important  to  inquire  how  far  they  corre- 
spond quantitatively  to  differences  in  the  energy  of  the  afferent  stimuli, 
i.e.  how  alterations  in  the  strength  of  stimulus  will  alfect  the  intensity 
of  the  resulting  sensation.  Whatever  form  of  stimulus  be  applied  and 
whatever    sense-organs  be  affected,  a  certain  minimum  intensity  of 


5:38  PHYSIOLOGY 

stimulus  is  necessary  for  it  to  be  effective,  i.e.  to  produce  a  minimum 
sensation.  This  strength,  which  varies  with  different  sense-organs,  is 
spoken  of  as  the  '  liminal  intensity,'  or  '  threshold  value  '  of  stimulus 
or  sensation  respectively.  As  the  strength  of  the  stimulus  is  increased 
above  this  minimal  amount  the  resulting  sensation  also  increases.  The 
change  in  intensity  of  sensation  is  not,  however,  indefinite.  When 
the  stimulus  is  increased  to  a  certain  amount  the  resultant  sensation 
becomes  maximal,  and  a  further  increase  in  the  stimulus  evokes  no 
further  increase  in  sensation.  In  fact  fatigue  of  the  sense-organs  or 
recipient  centres  of  the  brain  rapidly  sets  in,  so  that  the  sensation 
diminishes  even  with  increasing  strength  of  stimulus.  In  each  sense- 
organ  we  can  measure  the  amount  of  energy  which  must  be  applied 
to  it  in  order  to  evoke  a  minimum  sensation.  This  figure  varies  con- 
siderably with  the  physiological  condition  of  the  animal.  In  dealing 
with  reflexes  we  have  seen  that  the  motor  result  of  stimulation  of  a 
receptor  organ  varies  in  the  same  manner.  Thus  a  minimal  stimulus 
is  more  effective  if  repeated  a  few  times  at  definite  intervals  (summa- 
tion of  stimulus)  :  the  stimulus  which  is  submim'mal  may  become 
minimal  and  effective  as  a  result  of  repetition. 

Another  factor  which  intervenes  is  that  known  as  '  adaptation  ' — 
a  process  associated  to  a  certain  extent  with  the  phenomenon  of 
fatigue.  Adaptation  is  best  studied  in  the  case  of  the  eye.  Here 
the  dark-adapted  eye,  i.e.  one  that  has  been  kept  from  light  for  half 
an  hour,  will  react,  and  give  a  visual  sensation,  to  a  strength  of  stimulus 
which  is  only  one-fiftieth  of  the  minimal  stimulus  required  to  evoke 
sensation  in  the  eye  that  has  been  lately  exposed  to  light. 

Another  phenomenon  which  may  alter  the  strength  of  the  liminal 
intensity  of  stimulus  is  that  known  as  '  contrast.'  A  finger  plunged 
into  mercury  feels  a  ring  of  constriction  at  the  level  of  the  surface  of 
the  mercury,  i.e.  where  there  is  a  contrast  between  the  pressure  of  the 
mercury  and  the  absence  of  pressure  as  the  finger  emerges  into  the  air. 

The  strength  of  the  effective  stimulus  depends  also  on  the  number 
of  nerve-endings  simultaneously  excited.  Thus  when  deahng  with 
tactile  sensations,  or  sensations  of  pressure,  in  determining  the  minimal 
stimulus  we  must  take  into  account  the  area  stimulated,  and  we 
express  the  stimulus,  just  sufficient  to  produce  a  thresliold  sensation, 
as  '  weight  per  square  millimetre  of  surface.'  Moreover  the  rapid 
'  fatigability  '  or  adaptation  of  all  sense-organs  makes  the  rate  at  which 
the  stimulus  is  applied  of  considerable  importance.  Thus  when 
weight  was  applied  to  the  skin  of  the  ball  of  the  thumb  at  the  rate  of 
0"75  gramme  per  second  over  a  siuiace  of  21*2  sq.  mm.,  the  minimum 
load  necessary  to  evoke  a  distinct  sensation  was  2-5  grammes.  When, 
however,  the  rate  of  apphcation  of  the  weight  was  increased  to 
5  grammes  per  second,  distinct  sensation  was  produced  with  a  load  of 


RELATION  OF  SENSATION"  TO  STIMULUS 


539 


0*25  gramme.  It  is  evident  that  the  larger  the  area  of  the  skin 
stimulated  the  greater  will  be  the  minimal  weight  required,  since  this 
has  to  be  distributed  over  all  the  nerve-endings  contained  in  the 
area  of  skin  which  is  subjected  to  pressure,,  and  the  larger  the  area  the 
smaller  will  be  the  stimulus  applied  to  each  nerve-ending.  The  follow- 
ing figures  were  obtained  bv  von  Frev  on  different  regions  of  the  skin  : 


stimulated  surface  21-2  mm. 2 

Volar  side  of  ^^Tist  (Siibject  K) 
Ball  of  thumb  (Subject  K) 
Volar  side  of  A^Tist  (Subject  F) 

stimulated  surface  3  5  mm.  2 

Ball  of  thumb  (Subject  F) 
Tip  of  finger  (Subject  F)    . 
Volar  sid'  of  wrist  (Subject  F) 


Rate  of  loading  1-7  grm.  per  second. 
Threshold  value  of  stimulus  per  rnm.2 

0-024  -  0-038  grm. 
.     >0-189  -  0-039    „ 
.     >0-236  -  0-055    „ 

Kate  of  loading  3  grm.  per  second 
Threshold  value  of  stimulus. 

0-200  -  0045  grm. 

0-170  -  0-028    „ 

0-640  -  0-028    „ 


It  will  be  noticed  that  when  the  excited  surface  is  small  much 
greater  variations  are  found  from  spot  to  spot  in  the  size  of  the  minimum 
stimulus.  This  is  probably  connected  with  the  fact  that  the  sense- 
organs  for  pressmre  are  distributed  in  points  or  spots  over  the  surface 
of  the  skin,  so  that  when  the  stimulated  surface  is  small  the  threshold 
value  of  the  stimulus  will  be  determined  by  the  number  of  the  tactile 
spots  which  are  included  in  the  stimulated  area.  The  minimal  effective 
stimuli  in  the  case  of  the  other  senses  have  been  determined  as  follows  : 

(a)  HEARING.  A  musical  tone  can  be  heard  when  the  varia- 
tions of  pressure  in  the  air  amount  to  -OOOlXlOdQ  mm.  Hg.  with  an 
amplitude  of  vibrations  of  •0(X)000066  mm.  It  has  been  calculated 
that  the  intensity  of  the  work  performed  on  the  drum  of  the  ear  by 
such  a  minimal  tone  represents  an  average  of  5-1  X  10"-^°  ergs.  In 
the  case  of  noise  the  amount  of  energy  required  to  produce  a  minimum 
sensation  is  still  smaller.  A  distinct  sound  was  heard  when  a  weight 
G-7  milligrammes  was  allowed  to  fall  a  distance  of  1-2  mm.  on  to  an 
iron  plate  at  a  distance  of  500  mm. 

(6)  VISION.  The  minimum  intensity  of  light  necessary  to  arouse 
sensation  in  a  dark-adapted  eye  is,  according  to  Aubert,  equal  to  about 
one  three-hundredth  of  the  intensity  of  the  light  reflected  from  a 
piece  of  white  paper  which  is  being  lit  by  the  light  of  the  full  moon. 
The  amount  of  energy  involved  in  such  a  stimulus  is  much  smaller 
even  than  that  determining  a  sensation  of  touch  or  hearing. 

WEBER'S  LAW 

It  is  an  interesting  question  how  far  the  strength  of  sensation 

may  be  regarded  as  an  index  to  the  strength  of  stimulus.     Although 

it  is  easy  to  measure  in  absolute  terms  the  intensity  of  a  stimulus,  i.e. 

of  a  purely  physical   process,  there   is   no  means   by  which   we  can 


540  PHYSIOLOGY 

express  in  absolute  measure  the  strength  of  a  sensation.  We  cannot 
even  compare  the  strengths  of  two  sensations  differing  in  quahty  or 
modaHty ;  and  although  we  can  say  that  such  and  such  a  Hght  is 
stronger  than  another  light,  it  is  impossible  to  say  that  the  sensation 
resulting  from  the  stronger  is  two,  three,  or  more  times  that  of  the 
weaker.  In  measuring  the  efEect  on  sensation  of  increasing  the  stimulus 
we  are  therefore  reduced  to  using  the  smallest  wppreciable  increase  oj 
sensation  as  our  unit  of  sensation.  The  question  as  to  the  relation 
between  the  intensity  of  stimulus  and  the  intensity  of  sensation  resolves 
itself  into  an  inquiry  as  to  what  increase  in  a  given  stimulus  is  necessary 
in  order  that  it  may  evoke  an  appreciable  increase  in  sensation. 
Weber's  law  states  that  the  increase  of  stimulus  which  is  necessary  to 
produce  an  appreciable  increase  in  sensation  must  always  bear  the 
same  ratio  to  the  whole  stimulus.  Thus  if  we  fomid  that  we  could 
just  distinguish  the  difference  between  a  weight  of  10  oz.  and  a  weight 
of  9  oz.,  it  would  not  be  sufficient  to  add  one  ounce  to  a  weight  of 
10  lb.  in  order  to  produce  a  distinct  difference  in  sensation.  In  the 
latter  case  we  should  not  be  able  to  appreciate  any  difference  until 
we  had  added  a  pound,  i.e.  one-tenth  of  the  whole  stimulus  to  the 
weight.  We  can  distinguish  between  10  oz.  and  11  oz.,  or  between 
10  lb.  and  11  lb.,  but  not  between  10  lb.  and  10  lb.  1  oz. 

Several  methods  have  been  proposed  for  testing  the  limits  of  the 
applicability  of  this  law.     Of  these  the  most  important  are  : 

(1)  The  method  of  minimal  difference. 

(2)  The  method  of  average  error. 

In  the  first  method  we  find  by  trial  how  much  a  given  stimulus 
must  be  increased  in  order  to  evoke  an  appreciaole  increase  of 
sensation,  and  this  determination  is  made  for  a  number  of  stimuli  of 
different  intensity.  In  the  second  method  it  is  sought  to  find  a 
strength  of  stimulus  which  is  just  equal  to  another  stimulus  of  given 
mtensity.  It  will  be  found  that  errors  wnll  be  made  on  both  sides,  and 
the  average  error  is  taken  as  representing  the  minimum  difference, 
which  is  just  sufficient  to  cause  a  distinct  difference  of  sensation. 

In  all  sense-organs  Weber's  law  is  only  applicable  between  hmits, 
which  vary  with  each  sense-organ,  and  does  not  hold  either  for  very 
weak  or  for  very  strong  stimuli.  Within  these  limits  the  ratio  which 
an  increase  of  stimulus  must  bear  to  the  whole  stimulus  to  produce  an 
increase  of  sensation  may  be  given  approximately  as  follows  for  the 
different  sense-organs  : 

When  weights  are  placed  on  corresponding  points  of  two  sides  of 
the  body,  e.g.  on  the  two  hands,  we  can  appreciate  differences  of  about 
one-third  ;  if  the  contrast  be  successive,  i.e.  if  the  weights  be  placed  on 
the  same  spot  in  succession,  we  can  appreciate  differences  between 
one-fourteenth  and  one-thirtieth.     The  range  over  which  this  amount 


RELATION  OF  SENSATION  TO  STIMULUS  041 

of  accuracy  is  attained  extends  from  50  to  iOOO  grammes.  In  judging 
of  weights  with  the  help  of  movement  (the  method  one  ordinarily 
adopts)  the  limit  of  accmracy  is  about  one-twentieth  ;  for  sounds 
the  appreciation  of  difference  amounts  to  about  one-ninth.  The 
organ  which  is  most  susceptible  to  slight  changes  of  intensity  is  the 
eye  ;  by  this  organ  we  can  appreciate  differences  of  one  one-hundredth 
to  one  one-hundred-and- twentieth  in  the  total  illumination. 

FECHNER'S  LAW.  Fochner  has  endeavoured  to  give  a  mathematical 
expression  to  the  facts  described  imder  Weber's  law.  According  to  Weber 
the  proportion  between  the  increase  of  stimulus  necessary  to  cause  increase 
of  sensation  and  the  whole  stimulus  is  a  constant  for  all  intensities  of  excitation- 
Thus  if  C  is  a  constant 

R 

where  k  represents  the  smallest  appreciable  increase  of  sensation  evoked  by 
the  minimal  increase  of  stimulus,  R  is  the  stimulus,  and  AR  is  the  minimal 
increase  of  stimulus. 

If  the  same  relation  may  be  allowed  to  hold  for  infinitesimally  small  differ- 
ences of  sensation  and  infinitely  small  differences  of  stimulus,  this  formula 
maj^  be  expressed  by  the  equation  : 

dE  =  a^ 

R 

By  integration  we  ol)tain  the  expression  : 

E  =  C  log.  nat.  R 

i.e.  the  sensation  is  proportional  to  the  natural  logarithm  of  the  stimulus,  which 
is  Fcchner's  psycho-physical  law. 

In  view  of  the  fact,  however,  that  Weber's  law  only  holds  good  between 
certain  limits,  not  much  practical  value  can  be  attached  to  such  a  mathematical 
expression.  Moreover  Fechner's  calculation  is  based  on  the  unprovable  and 
unjustifiable  assumption  that,  within  the  limits  of  applicability  of  Weber's 
law,  the  smallest  appreciable  increase  in  sensation  is  always  the  same,  i.e.  that 
the  increased  sensation  which  is  evoked  by  the  addition  of  6  grammes  to  a 
weight  of  100  grammes  is  identical  with  the  inereai-ed  sensation  called  forth 
by  adding  60  grammes  to  an  initial  weight  of  1000  grammes.  Such  an  assump- 
tion does  not,  as  a  matter  of  fact,  agree  wth  our  own  experience  ;  and  it  is 
prol)ably  jiremature  here,  as  in  many  other  departments  of  biology,  to  attempt 
to  include  the  coniplex  of  variable  phenomena  presented  by  animal  functions 
within  tlie  Procrustean  bed  of  a  niatliematicMl  fonnnla. 


SECTION  II 

CUTANEOUS  SENSATIONS 

The  skin,  being  the  outermost  layer  of  the  bodV;  represents  the 
tissue  or  organ  by  which  the  organism  is  brought  into  relationship 
with  its  environment.  In  the  widest  sense  of  the  term  the  skin  is 
protective.  This  function  it  discharges  by  virtue  not  only  of  its 
physical  properties  but  also  of  its  rich  endowment  with  sense-organs, 
by  means  of  which  the  intracorporeal  events  can  be  correlated  with 
those  occurring  outside  and  immediately  affecting  the  organism. 

We  are  accustomed  to  distinguish  several  qualities  of  sensation 
among  those  having  their  origin  in  the  skin,  the  chief  of  which  are 
the  sense  of  touch,  including  that  of  discrimination,  the  sense  of  pain 
and  the  sense  of  temperature.  The  very  different  qualities  of  sensa- 
tion included  under  these  three  classes  suggest  that  there  may  be 
a  special  mechanism,  or  class  of  mechanism,  for  each  sense,  and  a 
careful  investigation  of  the  sensory  qualities  of  the  skin  surface  bears 
out  this  idea.  Isolated  stimulation  of  minute  areas  on  the  skin 
does  not  excite  all  the  sensations  together,  but  only  a  sense  of  touch  or 
of  pain,  or  a  sense  of  cold  or  warm.  We  are  therefore  justified  in 
dealing  with  each  of  these  sensations  separately. 

THE  TEMPERATURE  SENSE.  By  means  of  the  skin  we  can 
appreciate  that  a  body  ccming  in  contact  with  the  skin  is  either  cold 
or  warm.  If  the  body  is  at  the  same  temperature  as  the  skin,  as  a  rule 
no  sensation  of  temperature  is  excited.  It  was  formerly  thought 
that  the  sensations  both  of  heat  and  cold  were  determined  by  the 
excitation  of  one  and  the  same  end-organ.  Warming  of  this  end- 
organ  would  produce  a  sensation  of  warmth,  while  a  diminution  of 
its  temperature  would  produce  the  sensation  of  cold.  Careful 
investigations  by  Blix  and  Donaldson  of  the  distribution  of  the  tem- 
perature sense  has  shown  that  this  opinion  cannot  be  maintained.  If  a 
small  surface  warmed  to  a  few  degrees  above  the  temperature  of  the 
skin  be  moved  over  any  part  of  the  surface  of  the  body,  e.g.  the  back 
of  the  hand^  it  is  found  that  the  warmth  of  the  instrument  is  not 
appreciable  equally  at  all  parts  of  the  surface  of  the  skin.  At  some 
points  the  sensation  of  warmth  will  be  very  pronounced,  but  between 
these  points  the  sensation  of  warmth  may  be  entirely  wanting  and  the 

instrument  may  be  judged  to  be  of  the  same  temperature  as  the  hand 

542 


CUTANEOUS  SENSATIONS 


543 


itself.  In  this  way  a  series  of  '  warm  points  '  may  be  mapped  out. 
On  now  cooling  the  instrument  a  few  degiees  below  the  temperature 
of  the  surface  of  the  body  and  then  moving  it  over  the  surface  in  the 
same  way,  it  will  be  found  again  that  the  coolness  of  the  instrument  is 
only  appreciated  at  certain  points  which  can  be  regarded  as  '  cold 
points  '  and  as  containing  the  nerve-endings  by  the  excitation  of 
which  the  sensation  of  cold  is  produced.  If  the  warm  points  be 
pricked  out  in  red  ink  and  the  cold  points  in  blue-  ink  it  will  be  seen 
that  they  do  not  in  any  way  correspond. 

A  convenient  insti-ument  for  this  purpose  is  the  one  invented  by  Miescher, 
consisting  of  two  tubes  cemented  together  and  communicating  at  a  small 
flattened  extremity,  which  is  appUed  to  the  surface  of  the  skin  ;  through  the 
tubes  water  can  be  led  at  any  desired  temperature,  which  is  read  off  by  a  thermo- 
meter placed  within  the  tube.  Having  mapped  out  the  warm  spots  it  may  bo 
shown  that  they  are  excitable  by  means  of  mechanical  or  electrical  stimuli 
and  that  the  sensation  produced  is  the  same  as  if  they  had  been  excited  by 
their  adequate  stimulus,  viz.  rise  or  fall  of  tcmperatiire. 


Cold  spots.  Heat  spots. 

Fig.  240.     Heat  and  cold  spots  on  part  of  palm  of  right  hand. 
The  sensitive  points  are  shaded,  the  black  being  more  sen.sitive  than  the 
lined,  and  those  than  the  dotted  parts.     The  imshaded  areas  correspond  to 
those  parts  where  no  special  sensation  was  evoked.    (Goldscheider.) 

The  mapping  out  of  the  spots  is  rendered  difficult  by  the  irradiation 
of  the  sensation  produced  so  that  it  is  difficult  to  refer  the  sensation 
of  warmth  or  cold  definifely  to  the  point  stimulated.  An  investigation 
of  the  topography  of  these  warm  and  cold  spots  shows  that  the  appa- 
ratus for  the  appreciation  of  cold  is  much  more  extensively  distributed 
over  the  body  than  that  for  the  appreciation  of  warmth,  as  is  evidenced 
from  the  diagram  (Fig.  237)  giving  the  topographic  distribution  of  the 
cold  and  warm  sense-organs  on  the  back  of  the  hand .  The  temperature 
sense  is  best  marked  in  the  following  regions  of  the  body  :  the  nipples, 
chest,  nose,  the  anterior  surface  of  the  upper  arm  and  the  anterior 
surface  of  the  fore-arm,  and  the  surface  of  the  abdomen.  It  is  much 
less  marked  on  the  exposed  parts  of  the  body,  such  as  the  face  and 
hands,  and  is  but  slight  in  the  mucous  membranes.  Thus  it  is  possible 


544  PHYSIOLOGY 

to  drink  hot  fluid,  such  as  tea,  at  a  temperature  which  would  be  painful 
to  the  hand,  and  still  more  to  any  other  part  of  the  body.    The  scalp 
is  also  very  insensitive  to  changes  of  temperature.    The  acuteness  of 
the  temperature  sense  varies  considerably  with  the  condition  of  the 
skin  and  with  the  previous  stimulation  of  the  sense-organs.    The  sense 
is  most  acute  at  about  ordinary  skin  temperature,  i.e.  between  27^ 
and  32°  C.  At  this  temperature  the  skin  can  appreciate  a  difference  of 
y^  C.   When  the  skin  is  very  cold  or  very  hot  the  temperature  sense  is 
not  nearly  so  dehcate.  This  sense  presents  the  phenomenon  of  adapta- 
tion in  a  marked  degree.    It  is  a  familiar  experience  that  on  coming 
from  the  external  air  on  a  cold  day  into  a  warm  room  a  sensation  of 
warmth  is  experienced  all  over  the  body.   In  a  few  minutes  this  sensa- 
tion wears  oS.     On  now  leaving  the  room  to  go  outside  again,  the 
sensation  of  cold  is  at  once  appreciated ,  to  disappear  in  its  turn  after 
a  few  minutes.     The  effect  of  adaptation  is  still  better  shown    by 
the  experiment  of  taking  three  basins  of  water  a,  b,  and  c :   a  con- 
tains cold  water,  h  tepid  water,  c  hot  water.     The  left  hand  is  im- 
mersed in  the  cold  water  and  the  right  hand  in  the  hot  water  for  a 
few  minutes.     On  now  placing  both  hands  into  the  basin  of  tepid 
water  it  feels  hot  to  the  left  hand  and  cold  to  the  right  hand.     Such 
experiences  as  this  led  Weber  to  the  conclusion  that  the  essential 
stimulus  for  the  temperature  sense  was  not  the  actual  temperature  to 
which  the  sense-organs  were  subjected,  but  the  fact  of  a  change  of 
temperature.     He  imagined  that  while  the  temperature  sense-organs 
were  being  warmed  a  sensation  of  warmth  was  produced,  and  when 
their  temperature  was  being  lowered,  a  sensation  of  cold.     Such  a 
theory  would  not,  however,  account  for  the  fact  that,  above  a  certain 
temperature,  water  may  feel  warm  and  the  feeUng  may  continue  so 
long  as  the  skin  continues  to  be  stimulated.     On  a  cold  day  the  air 
may  feel  cold  to  the  face  and  the  feeling  may  last  the  whole  time  that 
the  face  is  exposed.     Moreover  we  have  in  the  temperature  sense 
conditions  which  remind  one  of  the  after-images  which  occur  in  the 
eye  and  which  will  form  the  subject  of  a  later  section.      If  a  penny 
be  pressed  on  the  forehead  and  then  removed  the  sensation  of  cold 
lasts    some  little  time  after  the  penny  has  been  removed.      In  this 
case  a  sensation  of  cold  is  produced  although  the  end-organs   are 
being  gradually  warmed  up   after  the   removal   of   the   penny.     In 
order  to  account  for  these  facts  Hering,  at  a  time  when  the  differen- 
tiation of  hot  and  cold   spots  had  not  yet  been  effected,  suggested 
that   the  temperature  sense-organs  could  be  regarded  as  having   a 
zero-point  at  which  no  sensation  was  produced.      If  their  tempera- 
ture was  raised  above  this  point  a  sensation  of  warmth  was  produced 
and  vice  versa.     The  zero-point,  however,  was  not  a  fixed  one,  but  could 
move  upwards  to  a  certain  extent  on  prolonged  exposure  to  high 


CUTANEOUS  SENSATIONS  545 

temperature,  or  downwards  on  prolonged  exposure  to  a  low  tempera- 
ture. In  the  Light  of  the  researches  of  Blix  and  Goldscheider  we  should 
have  to  apply  Hering's  theory  of  a  zero-point  to  each  of  the  tempera- 
ture end-organs  separately. 

A  cold  pencil  passed  over  a  warm  spot  evokes  no  sensation  what- 
soever. If,  however,  a  pencil  considerably  warmer  than  the  skin 
be  passed  over  a  cold  spot  this  may  be  excited,  so  that  the  paradoxical 
result  is  produced  of  a  sensation  of  cold  as  the  result  of  stunulation 
with  a  warm  body.  It  is  a  familiar  fact  that  the  immediate  effect 
of  entering  a  hot  bath  is  very  much  the  same  as  that  of  entering  a 
cold  bath,  viz.  a  rise  of  blood  pressure  and  contraction  of  the  un- 
striated  muscles  of  the  skin  and  hair  folUcles  with  the  production  of 
'  goose  skin.'  It  has  been  suggested  that  the  distinctive  quality  of  a 
sensation  of  hot  as  compared  with  that  of  warm  is  due  to  the  simul- 
taneous stimulation  of  warm  spots  and  cold  spots.  When  testing  the 
distribution  of  the  temperature  sense  it  is  found  that  the  sense  of  cold 
is  evoked  more  promptly  than  that  of  warmth.  This  is  interpreted 
as  showing  that  the  end-organs  for  the  warm  sense  are  situated  more 
deeply  than  those  for  cold.  We  have  no  evidence  as  to  the  histological 
identity  of  these  organs. 

THE  SENSE  OF  TOUCH 

By  means  of  the  sense  of  touch  we  arrive  at  a  conclusion  as  to  the 
quaUties,  such  as  shape,  texture,  hardness,  &c.,  of  the  bodies  with 
which  the  skin  is  in  contact.  In  this  judgment,  however,  very  many 
other  sensations  are  involved  besides  those  which  can  be  regarded  as 
strictly  tactile.  Thus  the  hardness  of  an  object  signifies  its  resistance 
to  deformation,  besides  its  power  of  deforming  the  skin  surface  with 
which  it  is  in  contact ;  the  former  quality,  i.e.  of  resistance,  is  one 
which  involves  the  muscular  sense,  since  we  judge  of  it  by  the  extent 
to  which  we  can  move  our  muscles  without  causing  any  alteration  of 
the  surface  of  the  body. 

The  tactile  sensibility  of  the  skin  as  a  whole,  like  its  temperature 
sensibility,  is  due  to  the  presence  in  it  of  a  number  of  touch  spots, 
i.e.  small  areas  which  are  extremely  sensitive,  separated  by  areas 
almost  or  entirely  insensitive  to  pressure.  The  tactile  sensibility  of 
any  part  is  proportional  to  the  number  of  such  touch  spots  present. 
If  the  calf  of  the  leg  be  shaved  and  then  tested  by  pressing  on  it  with 
a  fine  bristle  or  hair  it  will  be  found  that  the  minimal  stimulation 
used  evokes  sensation  only  at  certain  definite  points,  the  *  touch  spots.' 
In  a  square  centimetre  of  such  skin  there  may  be  about  fifteen  touch 
spots.  On  thrusting  a  fine  needle  into  one  of  these  spots  a  sharply 
localised  sensation  of  pressure  is  produced  unaccompanied  by  any 
painful  quahty  and  often  described  as   having  a  '  shotty  '  character, 

3') 


546  PHYSIOLOGY 

as  of  a  little  hard  objgct  embedded  in  the  skin  and  there  pressed 
upon.  These  touch  spots  are  arranged  chiefly  around  the  hairs, 
lying  usually  on  the  side  from  which  the  hair  slopes.  They  vary 
in  number  according  to  the  part  of  the  body  which  is  the  subject  of 
investigation.  Thus  the  dorsal  surface  of  the  finger  contains  about 
seven  times  as  many  touch  spots  as  an  equal  area  between  the  shoulders. 
In  some  regions,  such  as  the  skin  over  subcutaneous  surfaces  of  bone, 
as  much  as  one  centimetre  may  intervene  between  two  neighbouring 
touch  spots.  They  have  no  relation  to  the  warm  and  cold  spots  ; 
they  are  entirely  absent  from  the  cornea,  the  glans  penis,  and  the 
conjunctiva  of  the  upper  lid. 

The  adequate  stimulus  for  these  tactile  nerve-endings  is  not  so 
much  pressure  as  deformation  of  surface.  It  appears  to  matter 
little  whether  the  surface  be  deformed  by  pulling  it  or  by  pushing  an 
instrument  into  it.  The  ineffectiveness  of  mere  pressure  is  shown 
by  dipping  the  finger  into  a  vessel  of  mercury.  The  sensation  of 
pressure  is  only  noted  at  the  point  where  the  finger  passes  through  the 
surface  of  the  mercury,  and  this  is  the  only  part  where  there  is  an 
actual  deformation  of  the  skin,  due  to  the  sudden  passage  from  the 
pressure  of  the  mercury  to  the  negligible  pressure  of  the  outside 
air.  The  tactile  apparatus  is  smarter  in  its  response  than  any  other 
of  the  sense-organs.  On  this  account  stimuli  are  still  perceived  as 
discrete,  when  they  are  repeated  at  a  rhythm  which  would  result  in 
complete  fusion  in  the  case  of  any  of  the  other  sense-organs.  Thus 
if  a  bristle  be  attached  to  a  tunmg-fork  and  allowed  to  press  on  the 
skin,  the  vibrations  of  the  fork  are  perceived  by  the  ear  as  a  con- 
tinuous sound  and  by  the  skin  as  a  series  of  discontinuous  taps. 
Faradic  currents  when  applied  to  the  skin  can  be  perceived  as  separate 
when  repeated  at  the  rate  of  130  per  second.  The  sensations  evoked 
by  placing  the  finger  against  the  edge  of  a  cog-wheel  do  not  become 
continuous  until  the  wheel  is  revolving  at  such  a  rate  that  the  stimula- 
tion on  the  skin  by  the  serrations  occurs  at  a  greater  rate  than 
500  or  600  per  second.  The  tactile  apparatus  resembles  all  the 
other  skin  sense-organs  in  showing  adaptation.  A  stimulus  after 
continuing  for  some  time  may  become  ineffective.  We  are  usually 
entirely  imaware  of  the  stimulation  of  our  skin  by  the  pressure  of  the 
clothes,  and  even  an  unwonted  stimulation,  such  as  that  of  the  mucous 
membrane  of  the  mouth  by  a  plate  carrying  artificial  teeth,  though 
almost  unbearable  during  the  first  day,  rapidly  becomes  less,  and  in  a 
few  days  it  is  not  perceived  at  all. 

In  order  to  test  the  sensitiveness  of  touch  we  may  use  the  method 
introduced  by  Hensen,  viz.  the  bending  of  a  glass-wool  fibre.  We 
could  determine  the  pressure  at  which  any  given  fibre  will  bend,  and  if 
we  find  by  trial  the  fibre  which  just  evokes  sensation  when  pressed  on 


CUTANEOUS  SENSATIONS 


547 


the  skin,  we  know  exactly  the  force  which  we  are  applying  to  the 
skin.  Von  Frey  employed  hairs  of  different  thickness  for  the  same 
purpose  (Fig.  241).  The  following  represents  the  minimal  excita- 
bility of  the  surface  of  different  parts  of  the  body  when  tested  in 
this  wav. 


Tongue  and  nose 
Lips     . 

Finger-tip  and  for 
Back  of  finger 

'head 

r 

rm.  per  sq.  inn 
2 

2-5 
3 
5 

Palm,  arm,  thigh 
Fore- arm 

7 
8 

Back  of  hand 

12 

Calf,  shoulder 

16 

Abdomen 

26 

Outside  of  thigh 
Shin  and  sole 

26 

28 

Back  of  fore- arm 

33 

Loins 

48 

a                                            1 

Fig.  241.     Hair  mounted  on  a  wooden  handle,  and  used 
by  von  Frey  for  testing  tactile  sensibility. 


The  sensitiveness  of  the  sense-organs  in  the  skin  is  probably  much 
greater  than  that  of  the  nerve-trunks  themselves.  Thus  Tigerstedt 
found  that  the  minimal  mechanical  stimulus  necessary  to  excite  the 
exposed  nerve  amounted  to  0-2  grm.  moving  at  140  mm.  per  second. 
For  the  touch  spots  von  Frey  found  that  0-2  grm.  moving  at  0-17  mm, 
a  second  is  an  adequate  stimulus. 

In  testing  the  sensibility  of  any  surface  it  is  important  to  remember 
that  the  hairs  themselves  form  very  effective  tactile  organs.  The 
touch  spots  are  distributed  in  greatest  profusion  aroimd  hair  follicles, 
and  there  is  a  rich  plexus  of  nerve  fibres  round  the  root  of  each  hair. 
A  slight  touch  applied  to  the  hair  acts  on  these  as  on  the  long  end 
of  a  lever,  the  hair  being  pivoted  at  the  surface  of  the  skin,  so  that 
pressure  on  the  hair  is  transmitted,  increased  five  or  more  times  in 
force,  to  the  hair  follicle  and  the  surrounding  nerve-endings.  The 
actual  sensibility  of  any  part  is  therefore  much  diminished  by  removal 
of  the  hairs.  On  9  sq.  mm.  of  the  skin,  from  which  the  hairs  had  been 
shaved,  the  minimal  stimulus  necessary  to  evoke  a  tactile  sensation 
was  found  to  be  36  mg.,  whereas  on  the  same  surface  before  it  was 
shaved  2  mg.  was  effective. 


548 


PHYSIOLOGY 


WEBER'S  LAW.  The  smallest  increment  or  decrement  of  stimu- 
lus which  determines  a  perceptible  difference  of  sensation  must, 
according  to  Weber's  law,  always  bear  the  same  ratio  to  the  whole 
stimulus.  In  measuring  such  differences  it  is  best  to  apply  the  stimulus 
successively  to  the  same  surface  of  the  skin  rather  than  simultaneously 
to  adjoining  areas.  The  time  interval  between  two  successive  stimuli 
should  not  be  more  than  five  seconds  and  the  duration  of  the  stimuli 
should  be  equal.  Weber  found  that  in  the  terminal  phalanx  of  the 
finger  the  minimal  perceptible  difference  was  about  one-thirtieth, 
but  the  ratio  was  not  the  same  for  all  regions  of  the  skin  nor 
for  all  individuals.  The  following  represents  the  liminal  difference 
in  various  skin  regions  : 

Forehead,  lips,  and  cheeks  .  .  .     l/30th  to  l/40th 

Back  of  fore-arm,  of  leg,  and  of  thigh  -A 

back  of  hand,  and  first  and  second    1/lOth  to  l/20th 

phalanx  of  finger,  &c.    .  .  .  -' 

All  parts  of  the  foot,  surface  of  leg,  and 

tliigh ......     more  than  1/lOth 

THE  SPATIAL  QUALITY  OF  TOUCH.  DISCRIMINATION.  If 
any  part  of  the  skin  be  stimulated  the  subject  of  the  experiment 
can  tell  at  once  the  exact  situation  of  the  excited  spot.  If  two  points 
be  stimulated  simultaneously  excitation  is  perceived  as  double,  i.e.  as 
proceeding  from  two  points,  provided  the  distance  between  the  points 
exceeds  a  certain  amount,  varying  in  different  parts  of  the  body.  The 
power  of  discrimination,  i.e.  of  judging  whether  a  stimulus  is  single  or 
double,  can  be  tested  by  arming  the  pomts  of  a  pair  of  compasses 
with  small  pieces  of  cork  and  then  seeing  how  far  apart  the  points 
must  be  when  pressed  on  the  skin  in  order  that  the  stimulus  may 
be  perceived  as  double.  The  following  Table  represents  this  distance 
for  various  reoiions  of  the  body  : 


Distance  in  mm. 

Skin  region 

mm. 

Tip  of  tongue       .           ... 

11 

Volar  surface  of  finger  lip 

2-3 

Dorsum  of  tliird  ])lial:iiix 

6-8 

]*alm  of  hand       ..... 

.      11-3 

Back  of  hand       ..... 

.      310 

Back  of  neck        ..... 

,      .'i4-0 

Middle  of  back,  upper  arm,  and  thigh     . 

.      (17-1 

When  touch  spots  are  sought  out  for  stimulation  with  the  points 
of  a  compass,  the  distance  at  which  the  excitation  is  perceived  as 
double  is  much  diminished,  as  is  shown  by  the  following  Table  of 
distances  for  the  touch  spots  in  millimetres  : 


CUTANEOUS  SENSATIONS  r,.49 


Distance 

Skin  region 

of  touch  spots 

Volar  side  of  fingc^r  ti[)s 

01 

Palm  of  hand 

01 

Fore-arm  (flexor  side)  . 

0-5 

Upper  arm  . 

OG 

Back  .... 

0-4 

ipass  ijoiuts  are  perceiv 

ed  to  lie  i 

ipart 

with  a  spec 

tinctness  when  they  are  applied  to  touch  spots  lying  on  different  lines 
which  radiate  from  the  hair  follicles.  The  figures  given  in  the  first 
table  have  no  relation  to  touch  spots,  but  show  the  average  distance 
over  which  an  excitation  can  be  perceived  as  double. 

The  delicacy  of  discrimination  of  any  part  is  largely  associated 
with  its  mobility.  Thus  in  the  arm  the  delicacy  increases  continuously 
from  the  shoulder  to  the  finger-tip.  If  the  localising  power  for 
touch  on  the  shoulder  be  taken  as  100,  that  of  the  finger-tips  will  ba 
represented  by  2582.  In  the  same  way  there  is  a  continuous  decrease 
of  the  distances  of  discrimination  as  we  pass  along  the  cheek  from  the 
ear  to  the  lip,  i.e.  from  the  non-mobile  to  the  mobile  part.  The  power 
of  discrimination  is  increased  to  a  certain  extent  by  practice  and 
largely  diminished  by  fatigue.  Any  factor  which  diminishes  the  tactile 
sensibility  of  the  part,  such  as  cold,  will  also  diminish  the  power  of 
discrimination. 

The  fact  that  we  can  localise  the  point  of  stimulation  shows  that 
every  tactile  sensation  derived  from  the  surface  of  the  body,  besides 
the  qualities  of  intensity  and  extensity,  has  also  associated  with  it  a 
characteristic  quality  dependent  on  its  position.  This  locahsed 
quality  of  a  tactile  sensation  was  called  by  Lotze  '  local  sign.' 
Among  psychologists  there  has  been  much  discussion  as  to  how  far 
this  '  local  sign  '  is  an  inborn  attribute  of  the  sensation  of  every 
point  on  the  body  surface,  or  how  far  it  is  acquired  by  experience 
and  based  on  memory  of  movements  and  muscular  impressions. 
In  the  retina  we  have  a  sense-organ  which,  like  the  skin,  possesses 
local  sign,  but  in  far  higher  degree,  the  power  of  discrimination 
of  the  retina  being  three  thousand  times  as  great  as  that  of  the  most 
sensitive  part  of  the  skin.  Cases  of  congenital  cataract  occur  in  which 
the  subjects  have  been  blind  from  birth.  By  extraction  of  the  cataract 
we  can  give  such  persons  the  power  of  sight.  It  is  found  that  at 
first  there  is  no  power  of  localising  visual  impressions.  The  '  local 
sign  '  is  only  developed  in  response  to  experience,  by  comparing  simul- 
taneous visual,  tactile,  and  motor  sensations.  By  analogy  we  nn'ght 
ascribe  the  local  sign  of  cutaneous  sensations  to  a  similar  causation. 
Our  study  of  the  spinal  animal  has  indeed  given  us  a  physical  or 
liistological  conception  of  local  sign.  We  know  that  stimulation  of 
any  part  of  the  body  evokes  an  appropriate  reaction,  the  nature  of 


550  PHYSIOLOGY 

which  is  determined  by  the  central  connections  of  the  entering  nerve 
fibres.  A  fibre  entering  at  one  segment  must  therefore  come  into 
relation  with  a  different  set  of  motor  cells  from  those  which  are  set  into 
action  by  a  fibre  entering  one  segment  lower  down.  Every  nerve 
fibre  from  the  skin  will  therefore  have  an  appropriate  complex  of 
motor  paths  in  functional  connection  with  its  central  endings,  and 
when  the  activity  of  these  reflex  paths  comes  to  be  represented  in 
consciousness  it  is  evident  that  the  sensation  derived  from  each  point 
must  differ  from  that  derived  from  any  other  point  of  the  skin  by 
virtue  of  the  differing  motor  events  actually  or  potentially  excited 
from  the  two  points.  In  ascribing  therefore  '  local  sign  '  to  coincident 
muscular  sensations,  and  to  the  memory  and  experience  of  past 
movements,  we  are  giving  but  an  imperfect  explanation  ;  since  the 
difference  between  the  sensations  from  different  parts,  which  are  at 
the  bottom  of  our  powers  of  localisation,  has  its  origin  in  the  structure 
of  the  central  nervous  system  itself  and  is  present  from  the  very 
beginning  of  the  evolution  of  a  reactive  nervous  system. 

PROJECTION  OF  TOUCH.  Since  the  alterations  in  the  surface 
of  the  skin  which  give  rise  to  tactile  sensations  are  habitually  caused 
by  contact  with  external  objects,  we  come  to  regard  the  sensations 
themselves,  not  as  changes  in  the  skin,  but  as  qualities  of  the  object 
which  touch  the  skm,  i.e.  we  project  the  sensation.  The  projection  is, 
however,  not  so  great  as  in  the  case  of  visual  sensations.  Cutaneous 
sensations  we  always  consider  as  qualities  of  an  object  immediately 
affecting  and  altering  the  condition  of  ourselves,  whereas  the  visual 
sensations  are  referred  at  once  to  objects  lying  right  away  from  our- 
selves, so  that  we  are  not  aware  that  any  change  has  taken  place  in 
our  bodies  as  a  result  of  the  entering  of  rays  of  hght  into  the  eye. 

It  is  remarkable  to  what  extent  projection  of  touch  sensation 
may  occur.  Thus  a  surgeon  actually  lengthens  his  fingers  by  using 
a  probe.  When  he  is  probing  for  dead  bone  he  feels  the  gxating  of  the 
bone,  not  at  his  finger-tips,  but  he  projects  the  sensation  to  the  end 
of  the  probe.  In  the  same  way  tactile  sensations  evoked  by  the  con- 
tact of  bodies  with  the  insentient  endings  of  hair  are  referred  to  the 
ends  of  the  hairs  rather  than  to  the  hair  follicles  where  the  nerve 
impulses  actually  come  into  being. 

The  dependence  of  local  sign  on  habitual  experience  is  well  shown 
by  the  various  tactile  illusions,  such  as  the  well-known  experiment  of 
Aristotle.  If  we  cross  the  first  and  middle  fingers  and  bring  them 
in  this  position  in  contact  with  a  pea,  if  the  eyes  are  shut,  we  should 
at  once  say  that  two  peas  lay  under  the  fingers.  This  is  especially 
marked  if  the  pea  be  rolled  between  the  fingers.  The  two  sides  of  the 
fingers  which  come  in  contact  with  the  pea  usually  touch  two  different 
objects,  and  these  parts  of  the  skin  would  have  to  be  re-educated,  i.e. 


CUTANEOUS  SENSATIONS  551 

their  local  sign  would  have  to  be  changed  in  accordance  with  the 
changed  conditions,  before  the  pea  would  be  perceived  in  ita  true 
state  aa  single. 

THE  PAIN  SENSE 

When  the  pressure  of  a  hard  object  on  the  skin  is  increased  beyond 
that  necessary  to  evoke  a  tactile  sensation,  at  a  certain  pressure  the 
quahty  of  sensation  changes  and  it  becomes  painful.  For  the  evolu- 
tion of  the  race  as  well  as  for  the  preservation  of  the  individual  this 
pain  sense  is  all-important ;  it  is  the  expression  in  consciousness  of  the 
reflexes  of  self-preservation  which  can  be  evoked  in  the  spinal  animal 
by  stimuli  which  are  nocuous,  i.e.  calculated  to  do  actual  damage  to  the 
tissues  of  the  body.  Thus  when  a  sharp  point  is  pressed  on  the  skin 
the  sensation  becomes  painful  just  before  the  pressure  is  sufficient  to 
cause  penetration.  The  so-called  trophic  lesions  which  occur  in  parts 
devoid  of  sensation  are  determined  for  the  most  part  by  the  lack  of 
the  pain  sense  and  the  consequent  failure  of  the  preservative  reflexes 
of  the  part.  It  is  remarkable  that  pain  may  result  from  changes  in 
organs  which  are  devoid  of  ordinary  sensibility.  Thus  the  intestine 
may  be  cut,  sewn,  or  handled  without  arousing  any  sensation  what- 
soever. A  strong  contraction  of  the  muscular  wall  or  increased  dis- 
tension of  the  gut  will,  however,  evoke  a  griping  pain.  In  the  same 
way  the  ureters,  which  are  devoid  of  sensation,  can  give  rise  to  excru- 
ciating agony  when  they  are  contracted  firmly  on  a  retained  calculus. 

We  are  accustomed  to  distinguish  many  different  qualities  of  pain, 
but  on  analysis  it  will  be  found  that  these  qualities  depend  on  the 
nature  of  the  sense-organ  which  is  simultaneously  stimulated.  Thus 
a  burning  pain  denotes  simultaneous  stimulation  of  the  pain  sense  as 
well  as  of  the  nerve-endings  to  the  warm  spots.  A  throbbing  pain 
results  when  the  vessels  of  the  part  are  dilated  and  the  part  is  tense 
with  effused  lymph,  so  that  each  pulse  of  the  vessels  causes  an  exacer- 
bation of  the  painful  stimulation  and  perhaps  also  stimulation  of  the 
tactile  end  organs. 

The  sense  of  pain  has  often  been  ascribed  to  over- maximal  stimula- 
tion of  any  form  of  sensory  nerve.  Although  it  is  true  that  over- 
stimulation of  the  auditory  or  optic  nerve  by  a  loud  sound  or  a  bright 
light  may  be  extremely  unpleasant,  the  sensations  evoked  do  not 
partake  of  the  characters  of  painful  sensations  such  as  would  be 
produced  by  pricking  or  burning  the  skin.  Moreover  a  careful  investi- 
gation of  the  sensory  points  on  the  skin  brings  out  the  fact  that  there 
are,  besides  the  tactile  and  temperature  spots,  other  spots  from  which 
only  painful  sensations  can  be  evoked.  We  have  seen  already  that 
over-stimulation  of  a  touch  spot  does  not,  as  a  matter  of  fact,  cause 
pain.     The  pain  spots  which  are  distributed   among  the  touch  and 


552  PHYSIOLOGY 

temperature  spots  are  insensitive  to  a  low  grade  of  stiniiihis.  As  the 
strength  of  the  stimulus  is  increased  a  point  is  suddenly  reached  at 
which  the  sensation  evoked  is  painful.  Moreover  in  parts  of  the  body- 
tactile  and  temperature  sense  are  entirely  wanting,  though  painful 
impressions  can  be  easily  evoked.  The  best  example  of  this  is  seen  in 
the  cornea,  minimal  stimulation  of  which  evokes  pain,  but  nothing 
which  can  be  regarded  as  a  tactile  sensation.  The  specific  quality  of 
pain  sensation  is  shown  moreover  by  the  fact  that  in  many  cases  of 
disease  the  sense  of  pain  may  be  aboHshed  without  the  sense  of  touch. 
Such  a  patient  is  said  to  suffer  from  analgesia,  but  not  anaesthesia. 
When  pricked  on  an  analgesic  part  the  patient  can  say  that  he  is 
pricked,  but  has  no  objection  to  any  amount  of  repetition  of  the 
stimulus,  since  the  sensation  is  entirely  devoid  of  painful  character. 

THE  WORK  OF  HEAD  ON  CUTANEOUS  SENSIBILITY 
In  a  long  series  of  researches  on  man  Head  has  shown  that  three 
different  classes  of  sensations  may  be  evoked  by  stimuli  applied  to  the 
surface  of  the  body.  In  order  to  study  the  functions  of  the  afferent 
nerves  Head  has  investigated  not  only  the  condition  of  patients,  the 
subjects  of  accidental  division  of  cutaneous  or  other  nerves,  but  also 
(in  conjunction  with  Rivers)  the  effects  of  nerve  section  on  himself. 
In  the  first  place,  it  is  necessary  to  differentiate  deep  sensibility  from 
cutaneous  sensibility  proper.  After  desensitisation  of  any  given  area  of 
the  skin  it  is  still  possible  in  this  area  to  appreciate  deep  pressure  and 
pain,  and  the  localisation  of  the  situation  of  the  pressure  is  fairly 
accurately  carried  out.  On  the  other  hand,  the  sensations  of  light 
touch,  as  well  as  of  temperature  and  the  pain  evoked  by  a  light 
pin  prick,  are  absent.  The  sensations  of  pressure,  as  well  as  of  deep 
pain  or  pressure  pain,  are  therefore  carried  by  the  nerve*  of  deep 
sensibility.  These  nerves  are  not  the  cutaneous  nerves,  but  are 
derived  from  the  sensory  elements  in  the  muscular  nerves.  To  the 
fingers,  for  instance,  they  run  in  the  tendons  of  the  muscles.  Simul- 
taneous division,  as  by  a  circular-saw_cut,  of  the  cutaneous  nerves  and 
tendons  to  the  fingers  will  abolish  deep  as  well  as  superficial  sensibility. 
Deep  sensibility  must  therefore  be  classified,  anatomically  at  any  rate, 
with  the  '  organic  sensations  '  of  muscular  effort  and  of  position,  which 
will  be  dealt  with  in  a  subsequent  section. 

Cutaneous  sensibility  proper  Head  divides  into  two  categories, 
namely,  frotopathic  and  epicritic  sensibility.  These  two  forms  of 
sensibility  may  be  studied  separately  on  an  area  of  skin,  which  has 
been  desensitised  by  section  of  its  cutaneous  nerves,  during  the  process 
of  regeneration  of  these  nerves. 

PROTOPATHIC  SENSIBILITY  leturns  to  the  skin  at  an  interval 
of  seven  to  twenty-six  weeks  after  the  nerve  section.    At  this  time 


CUTANEOUS  8EN.SATTON8 


553 


it  is  posyible  to  appreciate  in  the  area  under  investigation  the  sensation 
of  'pain,  and  to  recognise  roiujJmess  of  an  object  rubbed  on  the  skin. 
Localisation  is  still  somewhat  diffuse  and  inaccurate,  so  that  the 
sensation  evoked  by  a  stimulus  of  the  protopathic  area  may  be  referred 
to  some  adjoining  normal  part  of  the  skin.  The  temperature  sense  is 
also  present,  but  of  a  low  grade.  Thus  heat  over  38°  C.  and  cold 
under  24°  C.  can  be  appreciated  as  such,  but  the  intervening  tempera- 
tures produce  no  sensation.  Sensations  evoked  in  the  protopathic  area 
are  strongly  endowed  with  what  may  be  termed  '  affective  '  character. 
Thus  painful  stimulation  is  much  more  unpleasant  when  applied  to 
this  area  than  would  a  similar  stimulation  be  when  apphed  to  a 
normal  area  of  sldn. 

In  contradistinction  to  the  deep  sensibihty  which  is  diffuse, 
protopathic  sensibility  is  distributed  in  spots,  so  that  heat  and  cold 
spots,  for  instance,  may  be  distinguished  as  on  the  normal  skin.  It  is 
interesting  that  the  glans  penis  is  normally  provided  only  with  proto- 
pathic sensibility. 

EPICRITIC  SENSIBILITY  does  not  return  to  the  desensitised  area 
until  one  to  two  years  have  elapsed  since  the  division  of  the  nerves. 
With  its  return  the  affective  character  of  the  protopathic  sensations 
at  once  disappears  and  is  replaced  by  an  accurate  discrimination  of  the 
nature  and  extent  of  tbe^^Stimulus ;  the  tactile  sense  proper,  i.e.  the 
appreciation  of  the  lightest  touch  applied  to  the  skin  and  its  accurate 
localisation,  belonging  entirely  to  the  epicritic  sensations.  The  power 
of  discriminating  the  distance  between  two  points  applied  to  the  skin 
simultaneously  is  also  a  function  of  the  epicritic  sensibility. 

With  the  discriminating  tactile  sense  returns  also  the  power  of 
appreciating  fine  differences  of  temperature,  i.e.  differences  between 
26°  and  37°  C. 

This  classification  may  be  summed  as  follows  : 


Deep  sensibility 


.     ,    ,.        r Pressure  sense 
including     ^^ 

°   V  Pressure  pain 


Protopathic  sensibility 
(strongly  affective) 


rSkin  pain 

]  Heat  over  38°  C. 

lColdimdcr24°C. 


Epicritic  sensibility 
(accurately  locali.sed) 


Tactile  sense  proper 
Pain  localisation 
Discriminalion 
Heat  and  cold  between 
26°  and  .T"  C. 


Head  and  Thompson  have  shown  that  on  entering  the  cord  these 
various  sensations  undergo  a  new  gi-ouping.  Thus  the  pain  impulses, 
which  arise  in  and  are  carried  bv  the  umscular  nerves,  the  nerves  of 


554  PHYSIOLOGY 

deep  sensibility,  unite  with  those  which  run  in  the  protopathic  system, 
so  that  a  lesion  of  the  cord  which  abolishes  the  sense  of  pain  will 
abolish  all  forms  of  pain,  whether  arising  from  the  skin  or  from 
the  underlying  tissues.  In  the  same  way  all  temperature  sensations, 
whether  the  fine  ones  of  the  epicritic  system  or  the  coarser  ones  of 
the  protopathic  system,  run  together  in  the  cord.  If  the  heat  sense 
IS  affected  by  a  lesion  of  the  cord  all  forms  and  all  degrees  of  the  sensa- 
tion are  affected  in  like  measure,  and  the  same  applies  to  the  sensations 
of  cold. 

THE  HISTOLOGICAL  CHARACTER  OF  THE  ELEMENTS 
INVOLVED  IN  CUTANEOUS  SENSATIONS 

A  very  large  number  of  different  forms  of  sensory  nerve-endings 
have  been  described  in  relation  to  the  skin.  Their  exact  allocation 
among  the  different  cutaneous  senses  presents  considerable  di£6cu]ties. 

As  regards  touch,  two  kinds  of  elements  are  probably  involved. 
In  the  first  place,  the  most  sensitive  tactile  apparatus  are  the  follicles 
of  the  short  hairs.  Around  these  folUcles  we  find  a  sheaf  of  nerve  fibres, 
some  of  which  end  in  the  hair  papilla  and  others  form  a  ring  near  the 
level  of  the  openings  of  the  sebaceous  glands.  The  other  tactile  end 
organ  is  Meissner's  corpuscle.  The  distribution  of  these  in  the  skin 
is  not,  however,  dissimilar  to  that  of  the  power  of  discrimination,  with 
which  they  may  be  specially  connected.  Other  end-organs  which  are 
supposed  to  be  stimulated  by  changes  of  pressure,  and  therefore  to 
be  tactile,  are  the  organs  of  Ruffini  which  occur  in  the  papillae  of  the 
palm  and  fingers,  and,  lying  more  deeply,  the  elastic  tissue  spindles 
as  well  as  the  Golgi  corpuscles  and  the  Pacinian  corpuscles  in  the  sub- 
cutaneous tissue. 

As  regards  pain,  we  know  that  in  the  cornea,  which  possesses  only 
the  pain  sense,  the  sensory  nerve-endings  are  in  the  form  of  branches 
of  axis  cylinders  among  the  epithelial  cells.  Similar  free  nerve- 
endings  occur  in  the  epidermis  all  over  the  body,  and  it  is  therefore 
imagined  that  these  have  the  special  function  of  subserving  the  pain 
sense.  We  have  at  present  no  evidence  as  to  the  histological  character 
of  the  organs  by  which  the  sensations  of  heat  and  cold  are  aroused. 


SECTION  III 

SENSATIONS  OF  SMELL  AND  TASTE 

Every  living  organism  shows  a  susceptibility,  i.e.  a  power  of  reac- 
tion, to  chemical  stimuli.  Thus  the  plasmodium  of  myxomycetes, 
placed  on  a  strip  of  filter-paper  of  which  one  end  is  immersed  in  an 
infusion  of  dead  leaves  and  the  other  in  distilled  water,  will  crawl 
along  the  paper  towards  the  infusion  of  leaves.  If  the  infusion  of 
dead  leaves  be  replaced  by  a  weak  solution  of  quinine,  the  plasmodium 
will  be  repelled  and  will  travel  along  towards  the  vessel  of  water. 
These  movements  of  attraction  and  repulsion  are  spoken  of  as  positive 
and.  negative  chemiotaxis  respectively.  A  similar  chemical  sensi- 
bility accounts  for  the  clustering  of  aerobic  bacteria  towards  the  surface 
of  a  fluid,  i.e.  where  the  density  of  oxygen  is  greater,  or  around  chloro- 
phyll-containing algae  which  are  giving  off  oxygen  in  the  sunlight. 
The  aggregation  of  leucocytes  round  microbes  or  other  foreign  particles 
in  the  tissues  is  also  determined  by  their  chemiotactic  sensibility. 
Chemiotaxis  then  represents  the  faculty  by  means  of  which  these 
minute  organisms  are  able  to  adapt  themselves  to  chemical  changes 
in  their  environment  and  to  react  to  chemical  substances  at  a  con- 
siderable distance  from  themselves.  If  we  could  endow  these  ele- 
mentary organisms  with  consciousness  and  with  a  sense  of  their 
surroundings,  we  should  have  to  say  that  they  became  aware  of  the 
presence  of  some  harmful  or  attractive  material  at  some  distance  from 
themselves.  The  sensation  they  received  from  these  distant  objects 
would  be  therefore  a  projected  sensation. 

On  the  other  hand,  a  chemical  sensibility  of  the  body  surface  or 
part  of  it  furnishes  the  criterion  by  which  particles  are  accepted  and 
ingested  as  food  or  rejected  as  useless  or  harmful.  Consciousness  in 
this  case  would  be  of  something  affecting  and  in  contact  with  some 
part  of  the  organism  itself.  The  sensation  would  not  be  projected 
further  than  the  periphery  of  the  body. 

These  two  kinds  of  chemical  sense — the  projected  and  the  surface 
sense — are  found  throughout  almost  all  classes  of  the  animal  kingdom, 
and  in  the  higher  animals  at  least  are  known  as  the  senses  of  smell  and 
taste.  The  former  sense  in  many  animals  attains  a  high  degree  of 
complexity  and  is  prepotent  in  determining  the  beliaviour  of  an  animal 
in  response  to  the  changes  in  its  surroundings.     In  the  elasmobranch 

555 


556 


PHYSIOLOGY 


fishes  the  olfactory  lobes  form  the  greater  part  of  the  higher  brain,  and 
extirpation  of  them  produces  a  loss  of  spontaneity  and  of  delayed 
reactions  similar  to  that  which  can  be  brought  about  in  higher  types 
by  extirpation  of  the  whole  of  the  cerebral  hemispheres. 

The  sense  of  taste,  on  the  other  hand,  is  only  used  for  sampling 
the  nature  of  substances  taken  into  the  mouth  and  determining  their 
ingestion  or  rejection.  It  is  therefore  much  simpler  in  its  extent  and 
more  susceptible  of  analysis. 


THE  SENSE  OF  TASTE 
The  end-organs  which  subserve  the  function  of  taste  are  repre- 
sented by  the  taste-buds.     These  are  oval  bodies  (Fig.  242)  embedded 

in  the  stratified  epithelium,  which  occur 
scattered  over  the  tongue,  a  few  being  also 
found  on  the  hard  palate,  the  anterior 
pillars  of  the  fauces,  the  tonsils,  the  back 
of  the  pharynx,  the  larynx,  and  the  inner 
surface  of  the  cheek.  On  the  tongue  they 
are  found  chiefly  in  the  grooves  around  the 
circumvallate  papillae  of  man,  and  in  the 
grooves  of  the  papillae  foliatae  of  rabbits. 
A  few  are  also  present  on  many  of  the 
fungiform  papilla.  They  consist  of  medul- 
lary and  cortical  parts,  the  former  being 
composed  of  columnar  or  sustentacular 
cells,  the  latter  of  thin  fusiform  cells,  the 
taste-cells  proper.  The  endings  of  the 
nerve  fibres  concerned  with  taste  end  in 
arborisations  among  these  taste-cells.  The 
peripheral  end  of  the  fusiform  cell  projects 
as  a  delicate  process  through  the  orifice 
of  the  taste-bud,  so  that  it  can  come 
in  contact  with  the  fluids  contained  in  the  cavity  of  the  mouth. 
A  sapid  substance,  to  stimulate  these  organs,  must  be  in  solution  ; 
hence  quinine  in  powder  is  almost  tasteless,  owing  to  its  s  ight  solu- 
bility in  neutral  or  alkaline  fluids. 

The  number  of  different  tastes  is  very  limited.  We  distinguish 
four  primitive  taste  sensations,  viz.  sweet,  sour,  bitter,  and  salt, 
some  authors  adding  to  this  an  alkaline  taste  and  a  metallic  taste. 
Many  substances  owe  their  distinctive  character  when  taken  into  the 
mouth  to  the  fact  that  they  stimulate  not  only  the  taste-nerves  but 
also  the  nerve-endings  of  common  sensation.  Thus  acids,  when  in 
weak  solution,  have  an  astringent  character  besides  their  sour  taste, 
and   if  strong   produce   a   burning  sensation.     The   primitive  taste 


ii^' 


Fig.  242.  Two  tastc-bucLs 
from  the  tongue, 
e.  Stratified  epithelium  ; 
■p,  opening  or  pore  of  taste- 
bud  ;  s,  gustatory  cells ; 
si,  sustentacular  cells. 

(KOLLIKER.) 


SENSATIONS  OF  SMELL  AND  TA>STE  557 

sensations  can  afEect  one  another  if  excited  simultaneously.  With 
weak  stimulation  one  taste  may  practically  annul  another.  Thus  a 
dilute  solution  of  sugar  is  rendered  almost  tasteless  by  the  addition 
to  it  of  a  few  grains  of  common  salt.  If  the  primitive  taste  sensations 
are  more  strongly  excited  we  get  a  mixed  sensation,  in  which  the 
components  can  still  be  distinguished.  Thus,  adding  sugar  to  lemon 
juice  not  only  diminishes  its  acidity  but  produces  a  mixed  sensation, 
the  quality  of  which  is  pleasant  and  in  which  the  components,  sour  and 
sweet,  can  be  easily  distinguished.  We  get  no  such  fusing  of  sensa- 
tions as  in  the  eye,  where  a  sensation  of  white  light  may  result  from 
stimulation  of  the  retina  by  two  complementary  colours.  Stimula- 
tion of  one  kind  of  taste-organ  heightens  the  sensibility  of  the  other 
taste-organs.  Thus  after  the  apphcation  of  salt,  distilled  water  may 
taste  sweet. 

That  these  primitive  taste  sensations  are  served  by  different 
nerve-endings  is  shown  by  the  following  facts  : 

(a)  The  tongue  is  not  equally  sensitive  at  all  points  to  all  four 
tastes.  Thus  the  back  of  the  tongue  is  more  sensitive  to  bitter,  while 
the  tip  and  sides  of  the  tongue  react  more  easily  to  sweet  and  sour 
substances.  A  difference  may  be  detected  between  even  the  circum- 
vallate  papillae  themselves  ;  a  mixture  of  quinine  and  sugar  applied 
to  one  papilla  may  excite  chiefly  a  bitter  taste,  while  with  an  adjacent 
papilla  a  sweet  taste  may  predominate. 

(6)  By  certain  drugs  we  can  depress  the  sensibility  of  the  taste- 
organs,  and  we  then  find  that  the  various  tastes  are  affected  to  different 
degrees.  Thus  on  painting  the  tongue  with  cocaine  the  first  effect 
is  a  diminution  of  tactile  and  pain  sensibility,  so  that  the  application 
of  acid  evokes  a  very  sour  taste  without  any  of  the  astringent  or 
stinging  sensations  normally  aroused  by  the  contact  with  the  acid. 
After  this  point  the  taste  sensations  are  also  abolished.  The  bitter 
sensation  disappears  first,  then  the  sweet,  and  then  the  sour,  while  the 
taste  of  salt  appears  to  remain  unaffected.  On  the  other  hand,  if  the 
leaves  of  Gymnema  sylvestre  be  chewed,  the  sensations  of  bitter  and 
sweet  are  abolished,  leaving  intact  the  acid  and  salt  tastes,  and  also  the 
general  sensibility  of  the  mucous  membrane. 

There  is  no  doubt  that  the  stimulating  effect  of  any  chemical 
substance  on  the  taste-nerves  has  relation  to  its  chemical  constitution. 
Thus  a  sour  taste  is  determined  by  the  presence  of  H  ions  ;  the 
alkaline  taste  by  that  of  OH  ions.  The  fact  that  certain  acids,  e.g. 
acetic,  have  a  stronger  sour  taste  than  would  corresjiond  to  their 
dissociation,  i.e.  to  the  number  of  H  ions  present,  is  due  to  the  fact 
that  these  acids  penetrate  more  easily  into  the  gustatory  cells  than  the 
mineral  acids  with  a  larger  dissociation  coefficient.  All  the  a-amino- 
acids   have   a    sweet   taste.     On   the   other  hand,  the    polypeptides 


558 


PHYSIOLOGY 


produced  by  the  combination  of  these  amino -acids,  as  well  as  the 
peptones  derived  jErom  the  hydrolysis  of  proteins,  have  a  bitter  taste. 
Most  of  the  alcohols  and  sugars  have  a  sweet  taste,  while  the  metallic 
derivatives  of  these  substances  are  bitter.  We  do  not  yet  under- 
stand the  law  which  determines  whether  any  given  substance  shall 
have  a  taste  at  all,  and  what  its  taste  should  be. 

The  nerves  of  taste  are  the  glossopharyngeal,  which  supplies  the 
back  part  of  the  tongue,  and  the  lingual  branch  of  the  fifth  nerve 
and  the  chorda  tympani,  which  supply  the  front  part.  All  these  fibres 
are  probably  connected  with  a  continuous  column  of  grey  matter 


Fig.  243.     Diagram  showing  origin  and  course  of  the  nerve  iibi'es  of  taste. 


in  the  brain  stem,  which  represents  the  splanchnic  afferent  nucleus 
of  the  fifth  nerve,  the  nervus  intermedins,  and  the  glossopharyngeal. 
Some  authors  have  stated  that  all  the  taste  fibres  of  the  fifth  nerve 
are  derived  from  the  glossopharyngeal  by  the  communication  through 
the  tympanic  plexus  and  the  chorda  tympani  nerve,  while  Gowers 
has  recorded  a  case  of  complete  unilateral  loss  of  taste  in  which  there 
was  a  lesion  destroying  the  fifth  nerve,  the  glossopharyngeal  being 
intact.  It  seems  possible  that  the  actual  region  of  the  taste-nerve 
may  vary,  the  fibres  running  to  the  splanchnic  column  of  grey  matter 
being  contained  sometimes  in  the  fifth,  sometimes  in  the  glosso- 
pharyngeal, and  sometimes  in  both. 

Most  of  our  so-called  tastes  should  rather  be  designated  flavours, 
and  are  dependent,  not  on  the  gustatory  nerves,  but  on  the  sense  of 
smell.  When  the  olfactory  sense  is  destroyed  very  little  difference  is 
to  be  perceived  between  an  onion  and  an  apple.  The  epicure  with  a 
^e  palate  has  really  educated  his  sense  of  smell  and  would  be  but 


SENSATIONS  OF  SMELL  AND  TASTE  559 

little  satisfied  with  the  simple  sensations  derived  from  his  four  sets 
of  gustatory  end -organs. 

THE  SENSE   OF  SMELL 

The  psychical  analysis  of  olfactory  sensations  is  rendered  difficult 
by  the  fact  that  this  sense  in  man  plays  but  a  small  part  in  his  usual 
adaptations.  We  have  thus  to  deal  with  a  sense  which  is  in  many 
respects  vestigial.  We  see  traces  of  great  complexity  in  its  possibilities 
of  performance,  but  are  baffled  in  our  endeavours  to  reduce  the  whole 
of  the  phenomena  to  the  simpler  factors  of  which  they  are  composed. 
Moreover,  like  all  vestigial  functions,  the  extent  to  which  the  sense  is 
developed  varies  from  one  individual  to  another.  Many,  for  instance, 
are  unable  to  appreciate  the  smell  of  vanilla,  of  hydrocyanic  acid, 
or  of  violets.  On  the  other  hand,  in  animals,  such  as  the  dog,  the 
olfactory  sense  seems  to  play  a  great  part  in  determining  behaviour, 
and  the  nervous  associations,  which  are  the  physiological  basis  of 
ideas,  must  in  these  animals  be  largely  connected  with  olfactory 
impressions.  Another  factor  which  diminishes  the  importance  of  olfac- 
tory sensations  in  man  is  the  ease  with  which  the  sense-organ  becomes 
fatigued.  It  often  happens  that  the  inmates  of  a  room  are  perfectly 
comfortable  and  may  perceive  no  fault  in  the  ventilation,  although  a 
new-comer  from  the  outside  at  once  remarks  that  the  air  is  foul. 

The  organ  of  smell  is  situated  at  the  upper  part  of  the  nasal  cavities. 
Here  the  mucous  membrane  covering  the  superior  and  middle  tur- 
binate bones  and  the  corresponding  part  of  the  septum  is  different 
from  that  covering  the  rest  of  the  nasal  passages.  Over  the  lower  parts 
of  the  nasal  cavities  the  mucous  membrane  is  of  the  ordinary  respira- 
tory type,  and  is  composed  of  ciliated  columnar  epithelium  contain- 
ing a  number  of  goblet-cells.  In  the  olfactory  part  the  epithelium 
is  much  thicker,  of  a  yellow  colour,  and  apparently  composed  of  a 
layer  of  columnar  cells  resting  on  several  layers  of  nuclei.  These 
nuclei  belong  to  the  olfactory  cells  proper,  true  spindle-shaped  nerve- 
cells  with  one  process  extending  towards  the  mucus  covering  the  free 
surface,  while  the  other  is  continued  along  channels  in  the  bone,  and 
through  the  cribriform  plate  as  one  of  the  non-medullated  olfactory 
nerve  fibres.  These  nerve  fibres  dip  into  the  olfactory  lobes,  where 
they  terminate  by  a  much-branched  arborisation  or  end  basket  in 
the  so-called  olfactory  glomeruli,  in  close  connection  with  a  similarly 
branched  dendrite  of  the  large  '  mitral '  cells  of  the  olfactory  lobe. 
The  axons  from  these  latter  carry  the  olfactory  impulse  towards  the 
rest  of -the  brain.  In  the  connective  tissue  basis  (dermis)  of  the 
mucous  membrane  are  a  number  of  small  mucous  or  serous  glands 
(Bowman's  glands)  whose  office  it  is  to  keep  the  surface  of  the 
membrane  constantly  moist. 


560  PHYSIOLOGY 

In  ordinary  respiration  the  stream  of  air  never  passes  higher 
than  the  anterior  inferior  border  of  the  superior  turbinate  bone,  so 
that  it  does  not  come  in  contact  with  the  olfactory  mucous  membrane. 
The  sensations  of  smell  which  are  aroused  during  ordinary  respiration 
depend  on  diffusion  from  the  respiratory  air  into  the  still  air  of  the 
upper  olfactory  portion  of  the  nasal  cavity.  The  direction  of  olfactory 
attention  is  achieved  by  sniffing  ;  in  this  act  the  nostrils  are  dilated 
and  the  direction  of  the  anterior  part  of  the  nasal  respiratory  chamber 
altered,  so  that  the  stream  of  entering  air  is  directed  towards  the 
upper  olfactory  portion  of  the  cavity. 

The  fact  that  we  are  able  to  perceive  smells  when  breathing 
normally  shows  that  the  odorous  substance  must  be  diffusible,  i.e. 
gaseous  in  form.  The  amount  of  substance  necessary  to  excite  sensa- 
tion is  extremely  minute.  Thus  -01  mg.  of  mercaptan  diffused  in 
230  cubic  metres  of  air  is  still  distinctly  perceptible.  In  this  case  a 
litre  of  air  would  contain  only  -00000004  mg.  of  the  substance,  and 
the  amount  actually  in  contact  with  the  olfactory  epitheUum  would 
be  still  smaller.  It  is  possible,  however,  to  show  the  presence  of  these 
odorous  substances  in  air  by  physical  means.  Tyndall  pointed  out 
that  air  containing  a  small  proportion  of  odorous  substances  absorbed 
radiant  heat  to  a  much  greater  degree  than  did  pure  air.  Thus  in 
one  experiment  air  containing  patchouU  absorbed  radiant  heat  thirty- 
two  times  as  strongly  as  the  pure  air.  Most  odorous  substances  possess 
large  molecules  and  have  therefore  high  vapour  densities.  On  this 
accoimt  the  smell  tends  to  hang  about  objects,  the  rate  of  diffusion 
of  the  vapour  being  only  small. 

Since  the  endings  of  the  olfactory  cells  are  bathed  in  fluid,  it  is 
evident  that  the  odorous  substances  must  be  dissolved  by  this  fluid 
before  they  can  excite  the  olfactory  nerve  fibres,  and  in  the  case  of 
aquatic  animals  we  know  that  the  projected  chemical  sense,  which  we 
call  smell,  can  only  be  aroused  by  substances  in  solution.  It  is 
difficult  to  show  in  man  that  the  nerve-endings  can  be  excited  by 
solutions.  Most  of  the  experiments  have  been  made  with  solutions 
which  had  an  injurious  effect  upon  the  olfactory  epithelium.  Accord- 
ing to  Aronsohn  it  is  possible  to  excite  sensations  of  smell  if  the  nasal 
cavity  be  filled  with  normal  saline  fluid,  containing  a  very  small  propor- 
tion of  the  odorous  substance.  To  this  experiment  it  has  been  objected 
that  it  is  almost  impossible  to  fill  the  nasal  cavities  without  leaving 
some  air  spaces  so  that  the  olfactory  sensation  obtained  might  have 
been  due  to  stimulation  of  the  olfactory  cells  in  such  a  space.  There 
is,  however,  no  a  'priori  reason  to  deny  the  probabihty  of  Aronsohn 's 
conclusions. 

Many  olfactory  stimuli  owe  their  pecuUar  character  to  the  simul- 
taneous stimulation  of  other  kinds  of  nerve-endings.     Thus  a  pungent 


SENSATIONS  OF  SMELL  AND  TASTE  561 

smell,  as  that  of  ammonia,  chlorine,  &c.,  involves  stimulation  of  the 
nerves  of  common  sensibility,  i.e.  the  fifth  nerve,  besides  stimulation  of 
the  olfactory  nerve. 

No  satisfactory  classification  of  smells  has  yet  been  made.  The 
following  facts  tend  to  show  that  there  are  a  number  of  primitive 
sensations  of  smell,  as  of  other  sensations  : 

(a)  Certain  individuals,  whose  olfactory  sense  is  in  other  respects 
normal,  have  no  power  of  distinguishing  some  odours. 

(b)  The  olfactory  sense  is  easily  fatigued.  If  it  be  fatigued  so  as 
to  be  absolutely  insensitive  for  one  kind  of  smell,  it  is  still  normally 
excitable  for  other  smells. 

(c)  It  is  possible  by  mixing  odoriferous  substances  in  certain 
proportions  to  annul  absolutely  their  effect  on  the  olfactory  organ. 
Thus  4  grm.  of  iodoform  in  200  grm. 
of  Peruvian  balsam  is  almost  odour- 
less, and  the  same  neutralisation  of 
odours  is  obtained  if  the  odour  of 
each  substance  be  allowed  to  act 
separately  on  each  side  by  tubes 
inserted  into  each  nostril. 


Fig.  244.    Zwaarclemaker's 
olfactometer. 


For  this  purpose  we  may  use  the  in- 
strument invented  by  Zwaardemaker, 
called  the  olfactometer.  This  consists  of 
a  porous  cylinder  into  which  is  inserted 
a  tube.     The  porous  cylinder  is  first  im-  \P 

mersed  in  the  fluid  whose  porous  qualities 

are  to  be  tested,  and  when  it  is  thoroughly  soaked  it  is  taken  out,  dried  outside 
by  a  cloth,  and  inside  by  drawing  air  through  it  for  a  short  time.  One  end 
of  the  bent  tube  is  then  inserted  into  the  cjiinder,  which  it  must  accurately 
fit,  while  the  other  end  is  placed  in  one  nostril.  The  small  wooden  screen 
shown  in  Fig.  244  serves  to  shut  off  the  smell  of  the  fluid  from  the  other  nostril. 
When  the  observer  breathes  through  the  bent  tube  the  amount  of  vapour 
taken  up  from  the  cylinder  -will  depend  on  the  amount  of  surface  exposed,  and 
therefore  can  be  diminished  or  increased  by  pushing  the  bent  tube  further 
in,  or  by  drawing  it  out.  If  the  tube  is  pushed  in  so  far  that  the  smell  is  only 
just  perceptible  the  length  of  the  tube  may  be  measured  and  taken  as  the 
liminal  intensity  of  stimulus  for  the  given  substances,  in  its  action  on  the  olfactory 
nerve-endings.  This  unit  was  called  by  the  inventor  of  the  instrument  an 
'olfactie.'  By  this  means  it  is  possible  to  make  quantitative  estimations 
of  the  olfactory  sense  on  one  individual  and  to  compare  them  with  observations 
made  on  other  individuals.  By  using  two  siicli  instruments  it  is  possible  to 
present  different  smells  to  the  two  nostrils.  One  obtains  in  this  way  com- 
bination effects  which  can  be  compared  to  the  ])henomenon  wiiich  \w  shall 
study  later  in  dealing  with  binocular  contrast. 


36 


SECTION  IV 

AUDITORY  SENSATIONS 

By  means  of  our  auditory  sensations  we  are  made  aware  of  such 
changes  in  our  environments  as  are  capable  of  giving  rise  to  a  dis- 
turbance which  can  be  propagated  through  the  surrounding  elastic 
medium,  the  air,  to  our  ears.  Any  sudden  jar  given  to  a  solid  body  sets 
up  vibrations  which  are  propagated  to  the  surrounding  air  as  sound 
waves,  i.e.  a  series  of  acts  of  condensation  and  rarefaction  spreading 
out  from  the  centre  of  disturbance,  like  the  waves  which  are  caused 
on  the  surface  of  a  pond  by  throwing  a  stone  into  its  middle.  "With 
a  delicate  tambour  we  can  record  these  changes  of  pressure  and  convert 
them,  by  means  of  a  lever  writmg  on  a  blackened  surface,  into  move- 
ments at  right  angles  to  the  direction  of  movement  of  the  surface. 
The  amplitude  of  vibration  of  the  membrane  will  be  proportional  to 
the  amount  of  compression  and  expansion  occurring  at  each  wave. 
These  waves  travel  through  the  air  at  the  rate  of  1 100  feet  per  second, 
their  wave  length  varying  with  the  number  of  vibrations  per  second. 
It  is  of  course  possible  to  get  vibrations  of  almost  any  number  per 
second.  Only  when  the  number  of  vibrations  fall  within  distinct 
limits  are  they  effective  in  producing  a  sensation  of  sound.  Before  we 
can  discuss  the  physiological  mechanism  of  hearing  we  nmst  have  a 
clear  idea  of  the  character  of  the  physical  change — the  stimulus — 
which  is  effective  in  evoking  an  auditory  sensation  and  determining 
its  quality. 

Sounds  may  be  divided  into  noises  and  musical  tones.  If  the 
vibrations  or  series  of  vibrations  arriving  at  the  ear  are  irregular  in 
character,  such  as  those  produced  by  striking  the  table  or  the  floor 
with  a  stick,  we  speak  of  the  resultant  sensation  as  a  noise.  If,  on 
the  other  hand,  the  vibrations  follow  one  another  at  a  regular  sequence 
and  possess  a  rhythm — if,  for  instance,  a  series  of  vibrations  be  imparted 
to  the  air  by  a  tuning-fork  vibrating  at  100  times  per  second — the 
effect  on  consciousness  is  that  of  a  musical  tone.  Of  course  there  is  no 
hard-and-fast  line  between  the  two  kinds  of  sound  ;  even  when  the 
prevalent  impression  is  that  of  a  noise  it  is  often  possible  to  pick  out 
some  series  of  vibrations  which  predominate  among  the  irregular  ones 
with  which  they  are  accompanied.     When  we  strike  a  single  stick  with 

a  hammer  the  effect  is  that  of  a  noise.     If,  however,  we  take  a  series  of 

562 


AUDITORY  SENSATIONS  563 

sticks  of  difEerent  lengths  and  strike  them  in  succession,  it  will  be 
noticed  that  the  sound  produced  by  each  stick  corresponds  to  a  dis- 
tinct note,  and  tunes  may  be  played  on  such  a  collection  of  sticks. 
On  the  other  hand,  the  tone  of  a  musical  instrument  maybe  so  harsh 
that  there  is  very  little  difference  between  it  and  a  noise. 

In  a  musical  tone  we  can  distinguish  various  characters  or  qualities  : 
(i)  The  loud7iess  of  a  tone  is  determined  by  the  amplitude  of  the 
vibrations  of  which  it  is  composed.  If  a  violin  string  be  bowed 
forcibly  the  excursion  of  its  string  at  each  vibration  is  greater  than  when 
it  is  bowed  gently,  and  the  amplitude  of  the  corresponding  alternating 
waves  of  sound  varies  in  proportion  to  that  of  the  vibrating  body  by 
which  they  are  started.  By  attaching  a  pointed  slip  of  paper  to  the 
end  of  a  tuning-fork  and  so  recording  its  vibrations  on  a  blackened 
surface,  it  is  easy  to  see  the  connection  which  exists  between  the 
amplitude  of  vibrations  and  the  loudness  of  the  sound  produced  by 
the  vibrating  fork. 

(2)  The  pitch  of  a  musical  tone  depends  on  the  rapidity  of  the 
vibrations  of  which  it  is  composed.  By  means  of  a  siren  we  can 
determine  the  number  of  vibrations  corresponding  to  each  note. 
As  the  speed  of  revolution  of  the  siren  is  increased,  and  therefore  the 
number  of  interruptions  per  second  of  the  stream  of  air  passing  through 
the  holes  in  its  disc,  the  note  appears  to  us  to  rise  continuously.  If 
we  take  two  tuning-forks,  one  vibrating  at  100  times  per  second  and 
the  other  vibrating  200  times  per  second,  the  pitch  of  the  latter  is 
observed  to  be  considerably  higher  than  that  of  the  former.  In  fact 
it  forms  the  octave.  If  the  number  of  vibrations  is  less  than  about 
thirty  per  second  no  musical  tone  is  produced,  the  individual  vibrations 
being  perceived  as  a  series  of  pulses  in  the  surrounding  air,  and  it  is 
only  when  we  increase  the  number  to  about  forty  per  second  that  we  are 
able  to  appreciate  the  pitch  of  the  note  produced.  As  the  number 
of  vibrations  per  second  is  increased  the  note  rises  steadily  without 
break  till  we  arrive  at  40,000  to  50,000  vibrations  per  second.  Above 
this  number  of  vibrations  the  human  ear  is  incapable  of  perceiving  any 
note  at  all,  though  it  is  probable  that  small  animals  can  perceive  notes 
still  higher  in  the  scale.  In  music  neither  the  lowest  nor  the  highest 
tones  are  used.  The  lowest  tones  of  the  large  organs,  that  of  the 
sixty-four  foot  pipe,  is  16  vibrations  per  second,  and  one  can  hardly 
speak  of  its  effect  as  that  of  a  musical  tone.  The  highest  notes 
employed  in  music  are  ai  and  c5  with  3520  and  4224  vibrations  per 
second  on  the  piano,  and  rf5  with  4752  vibrations  on  the  piccolo  flute. 
In  nmsic  therefore  we  only  employ  between  40  and  4700  vibrations 
per  second,  i.e.  about  seven  octaves.  The  manner  of  construction  of 
the  musical  scale  will  be  dealt  with  later. 

(3)  Timbre  or  quality  of  nuisical  sounds. 


564  PHYSIOLOGY 

When  the  same  note  is  sounded  on  different  instruments,  i.e. 
tuning-fork,  violin,  piano,  trumpet,  human  voice,  every  person, 
whether  he  has  an  educated  musical  ear  or  not,  can  say  at  once  what 
kind  of  instrument  is  being  used.  This  fact  shows  that  the  sound 
wave  produced  by  these  instruments  must  differ,  altogether  apart 
from  any  differences  in  amplitude  or  in  number  of  vibrations  per 
second,  and  if  the  sound  waves  produced  by  these  instruments  be 
recorded  an  actual  difference  is  found  in  the  shape  of  the  curve. 

If  a  stretched  wire  be  plucked  so  as  to  set  it  into  transverse  vibra- 
tions it  will  give  out  a  certain  note,  dependent  on  its  length,  its  thick- 
ness, and  the  tension  to  which  it  is  subjected.  If  its  length  be  halved 
it  will  give  out  a  note  which  is  of  double  the  number  of  vibrations 
per  second.  If  only  one-third  of  the  wire  be  set  into  vibrations  the 
sound  wave  produced  will  have  three  times  the  number  of  vibra- 
tions of  that  of  the  whole  string.  When  the  string  is  free  to  vibrate  as 
a  whole  the  segments  of  it  tend  to  vibrate  even  while  the  whole  string 
is  vibrating.  If  therefore  we  take  the  note  given  out  by  the  whole 
string,  the  '  fundamental  tone,'  as  corresponding  to  132  vibrations  per 
second,  there  will  also  be  a  series  of  notes  superadded  to  the  funda- 
mental tone  with  vibrations  per  second  in  the  ratio  of  1 ,  2,  3,  4,  5,  and 
6,  &c.  Thus  if  the  fundamental  tone  be  c,  the  overtones,  or  harmonics, 
will  be  produced  as  is  shown  below  : 


::a: 


:z2=nz^ 


b^ 


123456789  10 

Vibrations  per  Second 

132       2x132      3x132      4x132      5x132       6x132      7x132      8x132      9x132      10x132 

Nearly  all  musical  instruments,  as  well  as  the  apparatus  for 
producing  the  human  voice,  resemble  a  stretched  wire  in  giving  out 
overtones  in  addition  to  the  fundamental  tones,  and  the  difference  in 
the  quality  of  various  instruments  is  chiefly  determined  by  the  varying 
predominance  of  the  different  overtones.  In  some  the  higher  over- 
tones may  be  most  marked,  in  others  only  the  lower  overtones.  The 
tuning-fork  is  practically  the  only  instrument  the  note  of  which  is 
pure,  i.e.  free  from  harmonics  or  overtones.  It  must  be  remembered 
that  these  different  tones  arrive  at  the  external  ear  simultaneously. 
We  do  not  have  some  j^articles  of  air  vibrating  at  one  rate  and  other 
particles  at  another  rate,  but  all  the  simple  vibrations  of  which  the 
component  tone  is  composed  are  combined  together  to  form  a  com- 
pound wave,  the  shape  of  which  differs  according  to  the  constituent 
vibrations  of  which  it  is  made  up. 


AUDITORY  SENSATIONS  5<)5 

Thus  in  the  diagram  (Fig.  245)  the  wave  shown  by  the  contmuous 
line  is  compounded  of  the  series  of  simple  vibrations  represented  by 
the  different  dotted  lines.  The  components  of  such  a  compound 
curve  can  be  detected  if  the  sound  be  analysed  by  allowing  it  to  act 
on  resonators,  i.e.  on  instruments  which  can  be  set  into  vibration 
by  certain  simple  tones  of  which  the  component  tone  is  made  up. 
The  stretched  strings  of  a  piano  may  be  used  as  a  battery  of  such 
resonators.  If  the  dampers  of  the  strings  be  raised,  by  depressing 
the  loud  pedal,  and  a  note  be  then  sounded  into  the  piano,  it  may 
be  noticed  that  the  piano  gives  back  the  sound,  and  on' attaching 


Fig.  245.     d,  a  compound  sound  wave,  which  may  be  analysed  into  «,  the 
fundamental  tone,  and  b  and  c,  the  first  and  second  overtones.   (Hensex.) 

pieces  of  straw  to  the  various  strings  it  will  be  seen  that  only  certain 
straws  vibrate,  i.e.  those  on  the  strings  which  are  vibrating  to  the 
fundamental  tone  or  overtones  contained  in  the  sound  received  by 
the  piano.  For  the  analysis  of  sounds  the  resonators  devised  by 
Helmholtz  are  generally  employed.  These  consist  of  hollow  vessels, 
with  an  opening  at  one  end,  made  of  different  sizes,  so  that  each  will 
resound  only  to  a  definite  number  of  vibrations  per  second. 

BEATS  AND  DISSONANCE.  The  overtones  of  any  sound, 
at  any  rate  the  lower  ones,  are  at  considerable  distance  from 
one  another  on  the  musical  scale,  and  therefore  differ  consider- 
ably in  the  number  of  vibrations  of  which  they  are  composed. 
If  two  tuning-forks  be  sounded,  the  vibrations  of  which  differ  only 
by  one  or  two  per  second,  the  phenomenon  known  as  '  beats  '  is 
produced.  This  is  due  to  the  summation  or  interference  of  the 
waves  from  the  two  tuning-forks.  Su|)])osiiig  we  have  tuning-forks 
vibrating  one  at  100  and  the  other  at  101  times  a  second,  and  they 
start  vibrating  together.     At  first  the  waves  of  compression  started 


566 


PHYSIOLOGY 


by  each  fork  will  coincide  so  that  the  total  compression  of  the  air  at 
each  beat  will  be  the  compound  effect  of  the  compression  produced  by 
the  two  forks.  The  two  forks  therefore  will  reinforce  one  another. 
After  the  lapse  of  half  a  second  the  tuning-forks  will  be  at  different 
phases  of  their  excursion.  The  101  fork  will  be  moving  in  one  direction 
while  the  100  fork  is  moving  in  the  other,  so  that  the  compression 
produced  by  one  fork  coincides  with  the  expansion  of  the  air  produced 
by  the  moving  backwards  of  the  other  fork.  The  sound  produced 
by  one  fork  is  therefore  diminished  by  the  sound  produced  by  the 
other  fork,  and  the  total  sound  is  less  than  either  of  the  two  forks. 
At  the  end  of  one  second,  the  j^hases  of  the  two  forks  once  more 
corresponding,  we  shall  get  the  sound  increased  in  loudness  ;  thus 
there  is  an  alternate  waxing  and  waning  of  the  sound  which  recurs 
once  a  second  and  is  spoken  of  as  a  '  beat.' 

The  number  of  beats  per  second  may  be  used  to  determine  the 
differences  in  the  vibration  frequencies  of  two  forks.  Thus  two  forks 
vibrating  one  at  100  and  the  other  at  110  will  give  ten  beats  per 
second.  As  the  number  of  beats  increases  the  effect  produced  on  the 
ear  becomes  more  and  more  disagreeable,  just  as  the  rapid  alterna- 
tion of  illumination  produced  by  a  flickering  light  is  disagreeable  to 
the  eye.  This  objectionable  character  of  the  sound  is  most  marked 
when  the  beats  recur  at  about  thirty-three  times  per  second  ;  the 
individual  beats  are  not  then  distinguished,  but  we  speak  of  the  sound 
as  discordant  or  dissonant. 

CONSONANCE.  The  opposite  condition  of  consonance  or  harmony 
involves  therefore,  in  the  first  place,  an  absence  of  beats,  i.e.  of  rhythmic 
oscillations  of  amplitude  of  sound  waves  which  reach  the  ear.  The 
constituent  tones  and  overtones  must  be  capable  of  being  combined 
into  a  compound  wave  of  regular  amplitude  and  rhythm.  In  the 
most  complete  consonance  the  component  notes  are  identical  as  con- 
cerns at  any  rate  the  greater  number  of  their  overtones.  The  most 
complete  consonance  is  attained  when  the  two  notes  which  are  sounded 
together  are  identical.  Almost  as  complete  is  the  consonance  obtained 
when  a  note  is  sounded  together  with  its  octave.  The  other  consonant 
intervals  which  are  employed  in  music  are  as  follows  : 


Octave 
Fiftli 
Fourth 
Major  third 
Minor  third 
Minor  sixth 
Major  sixth 


It  will   be   noticed   that    in  all   these    consonant  combinations  the 
vibration  frequencies  of   the  notes  are  in  proportion  to  small  whole 


AIDITORY  SENSATIONS  567 

numbers.  If  we  put  down  not  only  the  fundamental  tones  of  these 
notes  but  also  their  overtones,  we  shall  see  that  there  is  considerable 
identity  as  regards  the  latter.  In  the  case  of  the  octave  the  two  are 
almost  identical,  the  only  difference  being  the  ground  tone  of  the  lower 
note,  and  the  identity  diminishes  as  we  pass  from  the  octave  through 
the  thirds  to  the  sixths.  The  overtones  which  are  identical  are  shown 
by  black  type  : 

Fundamental  tone  Overtone 

f  1    .     2   .     3   .     4   .     5   .     6   .     7    .     8   .     •»   .  10 
Octave  1  :  2  .  .  (  ^  4  g  g  10 

,^,  ,    ,    ^  I'  2    .     4    .     6    .     8    .   10   .  12    .   14    .    IG    .   18    .   21) 

l\ith2:3  -Is  6  9  12  1.5  18 


Fourth  :}  :  4  . 


I    3   .     0    .     y    .  12    .   15    .    18    .   21    .  24    .   27    .   30 
14         8  12  lU       20  24  28 


,,  .      ,,.,,-      (  4   .  8   .   12    .   l(j   .   20   .  24  .  28   .   32    .   36   .  40 

Majortlmd4:o    .^        .       ^^        j_             ^0  25       30       35  40 

,,.        „.,.,,      I  5    .  10    .    15   .   20   .   25    .  30    .   35    .   40    .   45    .   50 

Mmor  third  o:b    .^        ^        j,                  .,^  3^  3^       ^,      ^^ 


Major  sixth  3:5    . 
Second  8 : 0 
Seventh  8  :  15 


(    3    .     (J   .     9    .    12   .   15    .    18   .   21    .   24    .   27    .  30 
\       3  10  15  20  25  30 

r  8    .   16   .  24    .   32    .  4U    .    48    .   56   .   64    .  72    .  80 
I        9        18       27       36      45        54      63  72 

I    8    .    16    .   24    .   32    .  40   .    48    .  56    .   64    .   72    .   80 

I      15  30  45  60  75  90 


In  the  second  and  seventh,  which  are  discordant,  it  is  only  the 
eighth  overtones  which  are  identical,  while  the  fundamental  tones  will, 
as  a  rule,  be  so  close  together  that  beats  will  be  produced  of  a  number 
calculated  to  give  dissonance.  Since  the  phenomenon  of  beats  depends 
on  the  absolute  number  of  vibrations  per  second  they  are  more  easily 
produced  by  two  notes  near  together  at  the  lower  end  of  the  scale 
than  at  the  upper  end.  Thus  the  dissonance  is  quite  perceptible  in  a 
major  third  at  the  lower  end  of  the  piano,  but  disappears  at  the  upper 
part,  since  here  the  beats  produced  are  so  rapid  that  they  become 
imperceptible. 

The  various  notes  used  in  music  are  obtained  by  employing  the 
consonant  intervals  which  we  have  given  above.  The  major  chord 
is  composed  of  the  fundamental  tone,  the  major  third  and  the  fifth. 
If  we  take  '  c  '  as  the  fundamental  tone,  the  notes  of  the  chord  are 
c,  e,  g,  with  vibration  frequencies  corresponding  to  1,  ^.  i>.  i.e.  4.  5,  6. 
the  major  chord  from  g  is  g,  b,  d,  i.e.  three  notes  with  vibration  fre- 
quencies corresponding  to  |,  J^,  ^,  i.e.  4,  5,  0.     The  major  chord  from 


568 


PHYSIOLOGY 


the  fourth,  /,  is  /,  a,  c,  with  the  vibration  frequencies  -^,  ^,  ^^,  i.e. 
4,  5,  6.     The  C  major  scale  is  therefore  as  follows  : 

CDEFGAB      C 
1       9       5       4       3       5     15       2 

~      8       4       3^      2       3      8 

Different  instruments  are  tuned  to  one  normal  note,  i.e.  to  A 
with  440  vibrations  per  second  (this  note  varies  somewhat  in  different 
countries).  Taking  this  as  the  normal,  the  vibration  frequencies  of  the 
various  notes  used  in  music  are  given  in  the  following  Table  : 


Notes 

vibrations  per  second 

c  . 

33 

66 

132 

264 

528 

1056 

2112 

D 

37125 

74-25 

148-5 

297 

594 

1188 

2376 

E 

41-25 

82-5 

165 

330 

660 

1320 

2640 

F 

44 

88 

176 

352 

704 

1408 

2816 

G 

49-5 

99 

198 

396 

792 

1584 

3168 

A 

55 

110 

220 

440 

880 

1760 

3520 

B 

61-875 

123-75 

247-5 

495 

990 

1980 

3960 

COMBINATION  TONES.  If  two  tuning-forks,  with  an  interval  of 
one-fifth  between  them,  are  sounded  together,  we  may  hear  a  weak 
lower  tone,  the  pitch  of  which  is  an  octave  below  that  of  the  lower 
fork.  This  is  known  as  a  '  combination  tone.'  The  combination 
tones  are  divided  into  two  classes  :  (1)  '  difference  tones,'  in  which 
the  frequency  is  the  difference  of  the  frequencies  of  the  generating 
tones ;  (2)  '  summation  tones,'  which  have  a  pitch  corresponding  to 
the  sum  of  the  vibrations  of  the  tone  of  which  they  are  composed. 
By  means  of  appropriate  resonators  these  tones  can  be  reinforced, 
showing  that  they  have  an  objective  existence  and  are  not  produced 
in  the  ear  itself. 

Not  only  can  the  ear  appreciate  differences  between "  different 
musical  instruments,  dependent  on  the  varying  overtones  present 
in  the  sound  produced  by  each  instrument,  but,  when  a  number  of 
these  instruments  are  sounded  simultaneously,  the  ear  can  pick  out 
from  the  compound  sound  the  notes  due  to  the  individual  instrument, 
and  a  person  with  a  trained  ear  can  with  ease  name  notes  composing 
any  chord  struck  on  an  instrument  such  as  the  piano.  This  power  of 
analysis,  which  is  possessed  by  the  ear,  or  at  any  rate  by  the  auditory 
apparatus,  may  be  stated  in  the  form  of  the  law,  known  as  Ohm's  law, 
which  is  as  follows  : 

"  Every  motion  of  the  air  which  corresponds  to  a  composite  mass 
of  musical  tones  is  capable  of  being  analysed  into  a  sum  of  simple 
pendular  vibrations,  and  to  each  single  vibration  corresponds  a  simple 


Al'DITORY  SENSATIONS  569 

tone,  sensible  to  the  ear  and  having  a  pitch  determined  by  the  periodic 
time  of  the  corresponding  motion  of  the  air." 

THE  PHYSIOLOGY  OF   HEARING 

The  organ  of  the  ear  may  be  considered  as  consisting  of  an  accessory 
part  and  an  essential  part.  The  latter  is  formed  by  the  terminal 
expansion  of  the  auditory  nerve.  The  accessory  part  is  constructed  so 
as  to  bring  the  waves  of  sound  to  act  on  the  end  organs.  The  ear  is 
divided  anatomically  into  three  parts — the  external  ear,  consisting  of 
the  pinna  with  the  external  auditory  meatus  ;  the  middle  ear,  con- 
sisting of  the  tympanic  cavity  ;  and  the  internal  ear,  consisting  of  the 
osseous  and  membranous  labyrinths  with  the  terminal  branches  of 
the  auditory  nerve. 

The  external  ear  in  the  lower  animals  is  fashioned  so  as  to  collect 
sound  waves  from  different  directions.  To  this  end  it  is  provided 
with  muscles  and  in  many  cases  is  very  movable.  In  such  animals 
the  immediate  response  to  a  slight  sound  is  a  pricking  up  of  the  ears 
and  a  direction  of  their  orifices  towards  the  source  of  sound,  a  reflex 
direction  of  attention  which  in  man  is  replaced  by  a  conjugate  deviation 
of  the  two  eyes  towards  the  side  from  which  the  sound  comes.  The 
collecting  function  of  the  pinna  in  man  is  rudimentary  ;  in  fact  a 
man  can  hear  almost  as  well  with  his  ear  cut  off  as  normally. 

The  form  of  the  pinna  in  man  may  have  a  slight  influence  in  the  judgment 
of  the  direction  from  which  soimds  proceed.  It  has  been  noticed  that  a  com- 
pound tone  changes  sHglitly  in  quahty  as  its  position  in  relation  to  the  ear 
is  altered.  This  is  partly  due  to  the  fact  that  the  auricle  may  reflect  a  funda- 
mental tone  more  strongly  than  the  partial  or  the  converse.  According  to 
Rayleigh  this  difference  in  quality  is  determined  chiefly  by  the  fact  that  diffrac- 
tion of  the  soimd  waves  occurs  as  they  pass  round  the  head  to  the  ear  remote 
from  the  source  of  the  soimd,  so  that  the  partial  tones  reach  the  two  ears  in 
different  degrees  of  intensity  and  determine  a  difference  in  quality  of  the  sound 
as  heard  by  the  two  ears. 

The  external  auditory  meatus  in  man  is  about  one  inch  long  and 
directed  forwards,  inwards,  and  slightly  upwards.  Its  general  func- 
tion, other  than  as  a  mere  conductor  of  the  sound  waves,  is  to  protect 
the  delicate  vibrating  memhrana  tym/pani  which  closes  its  inner  end. 
Opening  on  the  skin  of  the  meatus  are  special  sebaceous  glands  which 
secrete  a  yellow  wax  {cerumen)  with  bitter  taste  and  peculiar  odour. 
The  wax  not  only  protects  the  cuticle  of  the  ear  and  the  membrana 
tympani  from  drying,  but,  together  with  the  hairs  at  the  orifice  of  the 
meatus,  serves  to  repel  insects  and  prevent  their  entering.  By  the 
length  of  the  meatus  moreover  the  drum  is  protected  from  draughts 
and  its  temperature  is  maintained  constant. 

The  sound  waves  which  ])ass  down  the  external  meatus  imjiinge 
on  the  drum  of  the  ear  and  set  this  into  vibration.     The  vibrations 


570  PHYSIOLOGY 

are  thence  transmitted  by  a  chain  of  three  small  bones,  the  auditory- 
ossicles,  across  the  cavity  of  the  tympanum  to  the  fluid  which  bathes 
the  terminations  of  the  auditory  nerve  in  the  internal  ear.  Since  the 
drum  of  the  ear  has'to  pick  up  and  transmit  vibrations  of  every 
frequency,  and  to  reproduce  accurately  in  its  movement  the  finest 
variations  of  pressure  in  the  course  of  the  wave,  it  is  essential  that 
it  should  be  devoid  of  any  periodicity,  i.e.  a  tendency  to  vibrate  at  a 


Fig.  246.  Diagrammatic  view  of  auditory  organ.  (After  Schafee.) 
1,  auditory  nerve  ;  2,  internal  auditory  meatus  ;  3,  utricle  ;  5,  saccule; 
6,  canalis  media  of  cochlea  ;  9,  vestibule  containing  perilymph  ;  12,  stapes  ; 
13,  fenestra  rotunda  ;  19,  incus  ;  18,  malleus  ;  17,  membrana  tympani ; 
16,  external  auditory  meatus  ;  14,  pinna  of  external  ear ;  23,  Eusta- 
chian tube. 

certain  frequency.  If  such  periodicity  were  present  the  ear  would 
pick  out  and  magnify  some  particular  overtone  present  in  the  com- 
pound tones  reaching  the  ear  and  magnify  it  to  the  exclusion  of  the 
other  overtones.  The  perfect  aperiodicity  of  the  tympanic  membrane 
is  secured  by  its  structure  and  attachments.  The  membrane  is 
composed  of  a  thin  layer  of  fibrous  tissue  covered  externally  with  skin 
,juid  internally  by  the  mucous  membrane  of  the  tympanum.  To  its 
inner  surface  is  attached  the  handle  of  the  malleus,  the  first  of  the 
auditory  ossicles,  along  its  whole  length.  This  attachment  of  an 
elastic  membrane  to  a  mass  of  bone  would  itself  tend  to  damp  any 
vibrations  of  the  membrane.     By  the  attachment  of  the  tendon  of 


AUDITORY  SENSATIONS  571 

the  tensor  tympani  muscle  to  the  inner  surface  of  the  handle  of  the 
malleus  the  middle  of  the  membrane  is  drawn  inwards,  so  that  it  forms 
a  cone  whose  walls  are  convex  outwardly.  The  membrane  is  built  up 
of  circular  and  radial  fibres,  the  circular  being  best  marked  towards  the 
periphery.  By  the  dragging  inwards  of  its  central  part  it  follows  that 
the  tension  of  its  constituent  fibres  varies  from  point  to  point  so  that 
each  bit  of  the  membrane  would  have  a  different  periodicity,  and  the 
membrane  as  a  whole  is  aperiodic. 

By  exposing  the  tympanum  from  above  it  is  possible  with  a  micro- 
scope to  observe  the  actual  movements  of  the  handle  of  the  malleus 
when  sound  waves  fall  on  the  tympanic  membrane.  The  maximum 
movements  at  the  apex  of  the  cone  may  be  taken  as  about  -04  mm., 
but  sounds  are  easily  audible  which  would  produce  movements  of  the 
tympanic  membrane  quite  imperceptible  under  this  method  of  examina- 
tion. On  the  inner  side  of  the  tympanic  membrane  is  the  tympanic 
cavity,  which  is  connected  in  front  with  the  pharynx  by  means  of  the 
Eustachian  tube.  This  is  opened  by  each  movement  of  swallowing, 
so  that  the  pressure  in  the  tympanum  is  kept  equal  to  that  of  the  out- 
side air.  When  the  Eustachian  tube  is  blocked  or  diseased  the  air  in 
the  tympanum  is  gradually  absorbed  and  the  patient  becomes  deaf  on 
that  side.  Stretching  across  the  tympanum,  from  the  membrana  tym- 
jjani  to  the  outer  wall  of  the  internal  ear,  is  a  chain  of  ossicles  which 
are  named  respectively  the  malleus,  the  incus,  and  the  stapes.  These 
ossicles  are  articulated  together,  so  that  a  movement  inwards  of  the 
malleus  causes  a  moveroent  inwards  of  the  base  of  the  stapes.  The 
malleus,  or  hammer  bone,  consists  of  a  thickened  head,  from  which 
two  processes  run,  viz.  the  manubrium,  which  is  attached  to  the  tym- 
panic membrane,  and  the  processus  gracilis,  by  which  it  is  anchored 
to  the  walls  of  the  tympanic  cavity.  By  means  of  three  ligaments  it  is 
so  fixed  that  it  is  capable  only  of  rotating  around  a  horizontal  axis, 
which  passes  through  the  anterior  ligament,  the  head  of  the  malleus, 
the  body  of  the  incus,  and  the  short  process  of  the  incus.  When  the 
manubrium  is  pushed  inwards,  a  part  of  the  malleus  above  this  axis 
must  move  outwards.  The  incus,  sometimes  known  as  the  anvil 
bone,  is  articulated  with  both  the  stapes  and  the  malleus,  and  a  liga- 
ment passes  from  its  short  process  to  the  posterior  wall  of  the  tympanic 
cavity.  The  posterior  surface  of  the  rounded  head  of  the  malleus  fits 
into  the  saddle-shaped  cavity  on  the  anterior  surface  of  the  incus, 
while  the  tip  of  the  long  process  of  the  incus  is  articulated  with  the 
stapes.  Movement  inwards  or  outwards  of  the  head  of  the  malleuflL 
causes  rotation  of  the  incus  round  an  axis  which  passes  from  the  tip 
of  the  short  process  through  its  body.  Thus  when  the  handle  of  the 
malleus  moves  inwards  the  greater  part  of  the  body  of  the  incus 
and  of  the  head  of  the  malleus  move  outwards  together,  while   the 


572  PHYSIOLOGY 

long  process  of  the  incus  moves  inwards.  The  stapes,  or  stirrup  bone,  is 
fixed  in  the  fenestra  ovalis  of  the  internal  ear,  in  the  inner  surface  of 
the  tympanum,  by  the  annular  ligament.  It  is  placed  almost  at  right 
angles  to  the  long  process  of  the  incus,  and  therefore  is  pressed  into 
the  foramen  ovale  when  this  process  moves  inwards.  The  breaking  up 
of  the  connection  between  the  tympanic  membrane  and  the  foramen 
ovale  into  three  bones,  connected  by  joints,  must  tend  to  prevent  any 
propagation  of  sound  by  direct  continuity  of  substance.  The  vibra- 
tions of  the  membrane  result  in  actual  movements  of  the  whole  bones, 
which  represent  a  chain  of  levers  reproducing  exactly  the  movements 
of  the  membrane.  In  the  transmission  of  a  sound  wave  from  the 
membrana  tympani  to  the  labyrinth  there  is  a  change  in  the  amount  of 
force  as  well  as  in  the  amplitude  of  the  movement.  The  three  bones 
can  be  regarded  as  forming  a  lever  with  two  arms,  one  of  which  is  the 
manubrium  of  the  malleus,  and  the  other  the  long  process  of  the 
incus.  The  length  of  the  former  is  to  that  of  the  latter  as  3  to  2,  so 
that  the  movements  transmitted  from  the  tympanic  membrane  to  the 
base  of  the  stapes  are  diminished  in  the  proportion  of  3  to  2  and  have 
their  force  increased  in  the  proportion  of  2  to  3.  Moreover,  as  the 
drum  of  the  ear  has  an  area  which  is  about  twenty  times  that  of  the 
foramen  ovale,  the  energy  of  its  movements  is  concentrated  on  an  area 
twenty  times  smaller.  Hence  the  pressure  of  a  sound  wave  acting  on 
the  tympanic  membrane  is  increased  thirty-fold  (|  x  20)  when  it  acts 
on  the  base  of  the  stapes. 

The  computation  of  the  actual  energy,  involved  in  the  movement 
of  these  structures  by  sound  waves,  which  are  just  perceptible  to  the 
ear,  yields  striking  results  as  to  the  extreme  sensitiveness  and  efficiency 
of  this  apparatus.  Lord  Rayleigh  has  estimated  that  the  amplitude 
of  the  movement  of  an  aerial  particle  involved  in  the  propagation 
of  sound  at  the  limits  of  audibility  is  less  than  one  ten-millionth 
of  a  centimetre.  By  other  methods  it  has  been  calculated 
that  the  ear  is  affected  by  vibrations  of  molecules  of  the  air  not 
greater  than  "0004  mm.,  which  is  equal  to  0"1  of  the  wave  length  of 
green  light.  These  results  show  that  the  amounts  of  energy,  required 
to  influence  the  eye  and  the  ear  respectively,  are  of  the  same  order  of 
magnitude. 

Two  muscles  are  found  in  the  tympanum,  viz.  the  tensor  tympani 
and  the  stapedius  muscles.  When  the  tensor  tympani  contracts  it 
draws  the  handle  of  the  malleus  inwards  and  so  increases  the  tension  of 
the  tympanic  membrane.  Direct  observation  has  shown  that  a  con- 
traction of  this  muscle  occurs  whenever  sounds  fall  on  the  membrane, 
and  that  this  reflex  contraction  is  bilateral  even  when  the  stimula- 
tion of  the  ear  is  unilateral.  The  stapedius  muscle  tilts  the  base  of  the 
stapes  and  at  the  same  time  draws  it  slightly  outwards,  so  relaxing 


AUDITORY  SENSATIONS 


573 


the  tympanic  membrane.  It  acts  therefore  as  an  antagonist  to  the 
tensor  tympani.  It  is  not  yet  kiKtwii  what  exact  part  this  muscle  plays 
in  audition. 

THE  END-ORGANS  OF  HEARING 
The  movements  of  the  stapes  are  communicated  to  a  fluid,  the 
perilymph,  and  by  this  to  the  endolymph,  which  immediately  bathes 
the  end-organ  of  hearing.  The  internal  ear  consists  essentially  of  a 
membranous  sac,  formed  originally  by  an  involution  of  the  epithelium 
covering  the  surface  of  the  embryo.  In  the  course  of  development  the 
sac,  which  is  filled  with  the  endolymph,  becomes  much  modified  in 
shape,  forming  from  before  backwards  the  scala  media  of  the  cochlea, 
the  saccule,  the  utricle,  and  the  three  semicircular  canals.     At  certain 


Fig.  247.     The  membranous  labyrmth. 
CM,   canalis    or   scala  media  of   the 
cochlea;  5,  saccule;  ?/,  utricle;  sc,  semi- 
circiilar  canals. 


Fig.  248. 


Vertical  .section  through  the 
cochlea. 


parts  of  its  inner  surface  thickenings  of  the  epithelium  occur,  which 
become  connected  with  the  terminations  of  the  eighth  nerve.  The 
membranous  lab}Tinth  lies  inside  a  bony  case,  the  osseous  labyrinth, 
from  which  it  is  separated  by  the  perilymph.  The  osseous  labyrinth  is 
formed  from  before  backwards  by  the  cochlea,  the  vestibule,  and  the 
semicircular  canals. 

The  utricle,  the  saccule,  and  the  semicircular  canals  are  concerned 
with  the  functions  of  equilibration.  At  present  we  have  only  to  deal 
with  the  structure  of  the  cochlea  and  the  end-organs  contained  in  the 
scala  media.  The  cochlea  is  a  spiral  tube  of  bone  20  to  30  mm.  long, 
divided  by  the  scala  media  into  two  parts,  viz.  scala  vestibuli  and 
scala  tympani,  which  are  continuous  at  the  apex  of  the  spiral  (helico- 
trema).  The  essential  part  of  the  organ  of  hearing  is  contained  in 
the  scala  media.  The  sound  waves  falling  on  the  ear  and  striking  the 
membrana  tympani  are  transmitted  with  diminished  amplitude  but 
increased  force  by  the  chain  of  ossicles  to  the  fenestra  ovalis  ;  through 
these  they  are  communicated  to  the  perilymph  which  fills  the 
vestibule.  The  vibrations  travel  from  the  vestibule  to  the  scala 
vestibuli.  Every  rise  of  pressure  in  this  canal  will  cause  an  actual 
movement    of   fluid    and    will   push   the   scala   media   towards  the 


574 


PHYSIOLOGY 


scala  tympani.  The  increased  pressure  thus  communicated  to  the 
scala  tympani  causes  a  bulging  of  the  membrane  closing  the  foramen 
rotundum.  Movement  inwards  of  the  stapes  causes  therefore  a  move- 
ment outwards  of  this  membrane  and  vice  versa,  and  the  wave  of  pres- 
sure in  passing  from  one  aperture  to  the  other  must  be  communicated 
to  the  scala  media  with  all  the  sensitive  structures  which  it  contains. 

The  scala  media  is  triangular  in  cross-section,  having  its  apex 
at  the  spiral  lamina  and  its  base  at  the  outer  wall  of  the  cochlea.     It 


Fig.  249.  Vertical  section  of  the  first  turn  of  the  human  cochlea.  (G.  Retzius.) 
s.v,  scala  vestibuli  ;  s.t,  scala  tympani ;  d.c,  canal  or  duct  of  the  cochlea  ;  sp.l, 
spiral  lamina  ;  n,  nerve  fibres  ;  l.sp,  spiral  ligament ;  str.v,  stria  vascularis  ;  s.sp, 
spiral  sulcus  ;  B,  section  of  Reissner's  membrane  ;  /,  limbus  laminae  spiralis  ;  m.t, 
membrana  tectoria  ;  tC,  tunnel  of  Corti ;  b.m,  basilar  membrane  ;  h.i,  h.e,  internal 
and  external  hair-cells. 


is  separated  by  the  membrane  of  Reissner  from  the  scala  vestibuli  and 
by  the  basilar  membrane  from  the  scala  tympani.  The  basilar  mem- 
brane is  composed  of  a  number  of  elastic  fibres,  which  pass  in  a  radial 
direction  from  ih6  spiral  lamina  to  the  spiral  crest  on  the  outer  wall 
of  the  cochlea.  The  length  of  these  fibres  increases  from  0-041  mm.  at 
the  base  of  the  cochlea  to  0495  mm.  at  the  helicotrema. 

The  end-organ  of  the  auditory  nerve  is  represented  by  theorgan 
of  Corti,  which  rests  on  the  basilar  membrane  (Fig.  250).  It  consists 
of  a  double  row  of  stiff  cells,  the  inner  and  outer  rods  of  Corti,  which  run 
throughout  the  whole  length  of  the  scala  media  and  are  surrounded  by 
sense  epithelium,  the  hair-cells.     On  the  inner  side  of  the  rods  of  Corti 


AUDITORY  SENSATIONS 


575 


there  is  a  single  row,  on  the  outer  side  three  rows  of  hair-cells.  Between 
the  hair-cells  are  the  sustentacula!  cells,  or  cells  of  Deiters,  the  peri- 
pheral processes  from  which  join  together  so  as  to  form  a  reticulate 
membrane  over  the  hair-cells,  the  hairs  themselves  projecting  through 
orifices  in  the  membrane.  Resting  on  the  upper  surface  of  the  mem- 
brana  reticularis  is  the  membrana  tectoria.  To  this  membrane  is  often 
ascribed  a  damping  ef!ect  on  the  vibrations  of  the  structures  below. 
Any  movement  of  the  basilar  membrane  would  be  transmitted  to  the 
rods  of  Corti,  and  by  these  to  the  overlying  hair-cells.  With  every 
vibration  these  would  move  in  the  line  of  their  long  axis  so  that  their 
hairs  would  move  up  and  down  in  the  membrana  reticularis  and 
possibly  strike  against  the  under  surface  of  the  membrana  tectoria. 


B.M 


Fig. 


2.50.      .Section  thiough  the  end-organ  of   the  auditory  nerve  in  the 
cochlea  (organ  of  Corti). 
BM,  basihu-  membrane  ;     c,  canal  of  Corti ;     RC,  rods  of  Corti ;    ih  and 
OH,  inner  and  outer  hair-cells ;   sc,  sustentacular  cella;  An,  auditory  nerve ; 
mt,  membrana  tectoria. 


The  fibres  of  the  auditory  nerve  pass  up  through  the  column  of  the 
cochlea,  through  the  bipolar  ganglion-cells  which  form  the  spiral 
ganglion,  and  then  out  along  grooves  in  the  spiral  lamina  to  end  in 
arborisations,  partly  in  the  inner  hair-cells  and  partly  among  the  outer 
hair-cells. 

The  complexity  of  the  structure  above  described  suggests  that  a 
large  amount  of  discriminating  and  analysing  power  possessed  bv  the 
ear  for  sounds  of  different  qualities  is  determined  by  the  differentia- 
tion of  the  end -organ  itself.  Not  only  are  we  able  to  appreciate 
differences  in  amplitude  and  pitch  of  the  sound  waves  which  arrive 
at  the  ear,  but  we  are  also  capable  of  analysing  the  compound  sounds 
and  determining  the  simple  tones  out  of  which  they  have  been  com- 
posed. This  power  of  analysis  nuist  be  due  either  to  the  presence  of 
some  battery  of  resonators  in  the  end-organs  of  the  auditory  nerve, 
or  to  the  existence  of  a  large  number  of  different  nerve  fibres,  each  of 
which  is  excited  only  by  a  distinct  number  of  vibrations  per  second,  or. 
finally,  we  must  assume  that  the  end-organ  of  hearing  is  affected  as  a 
whole  and  that  the  nerve  fibres  transmit  to  the  brain  the  different 
forms  of  wave  caused  by  various  complex  sounds,  the  analysis  being 


576  PHYSIOLOGY 

carried  out  in  the  cerebral  cortex  itself.  This  last  hypothesis,  the 
relegation  of  the  powers  of  analysis  to  the  cerebral  cortex,  is,  at  the 
present  time  at  any  rate,  equivalent  to  giving  up  any  attempt  to 
explain  the  power  of  analysis  possessed  by  the  organ  of  hearing.  On 
the  other  hand,  the  complex  structure  of  the  organ  of  Corti  suggests 
that  here  we  have  an  actual  battery  of  resonators,  by  means  of 
which  sense  waves  are  analysed  into  their  components.  This  is 
Helmholtz's  theory  of  the  function  of  the  cochlea.  It  assumes  that 
in  the  organ  of  Corti  there  are  vibrating  structures  tuned  to 
frequencies  within  the  limits  of  hearing,  viz.  from  30  vibrations 
to  about  4000  vibrations  per  second.  We  can  distinguish  notes  in 
the  middle  of  the  musical  scale  which  differ  from  one  another  only 
by  0-3  to  0'5  vibration  per  second.  Within  the  limits  of  this  scale 
we  should  therefore  require  about  4200  resonators  in  the  ear.  In 
order  to  account  for  the  sensitiveness  of  the  ear  to  sounds  below  40 
vibrations  and  above  4000  per  second,  we  might  allow  another  300 
vibrators,  so  that  4500  different  resonators  would  be  necessary  alto- 
gether. Helmholtz  at  first  thought  that  these  resonators  were  repre- 
sented by  the  arches  of  Corti,  but  on  Hensen  pointing  out  that  the 
basilar  membrane  was  composed  of  fibres  varying  from  0041  to  0-495 
mm.  in  length,  he  concluded  that  it  was  probably  the  breadth  of  the 
basilar  membrane  which  determined  the  tuning  to  any  particular  note. 
This  membrane  from  its  structure  behaves  like  a  system  of  stretched 
strings  bound  together  by  a  semi-fluid  substance.  The  parts  of  the 
membrane  near  the  fenestra  rotunda  would  be  adapted  for  the  higher 
notes,  while  those  near  the  helicotrema  would  vibrate  to  deep  tones. 
Each  fibre  would,  by  its  vibration,  set  the  overlying  part  of  the  organ 
of  Corti  into  vibration,  so  that  each  nerve  fibre  composing  the  auditory 
nerve  would  be  stimulated  by  a  different  note.  Miiller's  law  of  specific 
irritability  is  thus  observed,  each  nerve  fibre  transmitting  an  impulse 
which  excites  one  quality,  and  only  one  quality,  of  sensation.  When  a 
compound  wave  falls  on  the  organ  of  Corti,  it  is  actually  resolved  into 
its  simple  component  waves  by  the  fibres  of  the  basilar  membrane,  and 
we  therefore  get  stimulation  of  a  number  of  nerve  fibres  and  a  sensa- 
tion produced  which  is  a  true  mixed  sensation  compounded  of  a  number 
of  simple  tone  sensations.  By  an  effort  of  attention  therefore  it  is 
possible  to  pick  out  from  a  mixed  sensation  its  different  components, 
and  in  this  way  we  may  explain  the  analytic  powers  of  the  ear. 

Certain  observations  on  fatigue  of  the  auditory  fibres  support  the 
notion  that  each  fibre  reacts  to  notes  of  one  pitch,  and  only  to  these 
notes.  If  the  vibrations  of  a  tuning-fork  be  conducted  by  two  tele- 
phones to  both  ears  the  sound  appears  to  come  from  somewhere  in 
front  of  the  middle  line  of  the  body.  If  the  sound  be  transmitted  to 
one  ear  for  some  time  so  as  to  produce  a  condition  of  slight  fatigue, 


AUDITORY  SENSATIONS  577 

and  then  the  other  telephone  be  held  up  to  the  other  unfatigued  ear, 
the  sound  is  at  once  referred  to  the  unfatigued  side.  In  this  localised 
projection  of  the  sound  waves  we  have  a  simple  means  of  judging  of 
the  presence  or  absence  of  the  apparatus  in  one  ear  or  the  other.  It 
was  pointed  out  by  Bonders  that,  when  one  ear  was  fatigued  by  a  note 
of  360  vibrations  per  second,  and  immediately  afterwards  a  note  of 
365  vibrations  per  second  was  conducted  equally  to  both  ears,  no  trace 
was  perceptible  of  fatigue,  the  sound  being  located  exactly  in  tlie 
median  line.  We  are  therefore  justified  in  concluding  that  the  end- 
organ  of  the  nerve  fibre  which  carries  the  nerve  impulses  corresponding 
to  a  vibration  frequency  of  360  per  second  is  not  the  same  as  the  nerve 
fibre  or  end  apparatus  which  evokes  the  sensation  corresponding  to  a 
note  of  365  vibrations  per  second.  If  this  theory  is  correct,  destruc- 
tion of  the  lower  part  of  the  cochlea  should  abolish  the  power  rf 
appreciation  of  high  notes,  while  damage  to  the  region  of  the  helico- 
trema  should  impair  sensibility  to  low  notes.  Certain  results  of 
experiments  on  dogs  afford  confirmation  of  this  view,  although  all 
such  results  involving  judgment  of  the  powers  of  appreciation  of  high 
or  low  sounds  respectively  possessed  by  animals  must  be  received  with 
caution.  A  few  isolated  cases  have  been  recorded  in  man  in  which 
atrophy  of  the  nerve  fibres  supplying  the  lower  whorl  of  the  cochlea 
was  attended  by  total  want  of  perception  of  high  tones. 

According  to  Rutherford,  the  whole  of  the  basilar  membrane,  and  therefore 
of  the  auditory  hairs,  vibrates  equalh'  to  every  note,  just  as  the  plate  of  a 
telephone  receiver  reproduces  faithfully  the  shape  of  the  vibrations  impinging 
on  the  transmitter  of  the  telephone.  This  '  telephone  theory,'  as  it  has  been 
called,  relegates  the  whole  work  of  analysis  to  the  central  nervous  system, 
and  gives  us  no  clue  as  to  how  such  an  act  of  analysis  may  take  place.  One 
would  imagine  that  a  much  simpler  apparatus  than  that  represented  by  the 
organ  of  Corti  would  be  sufficient,  if  no  analysis  of  the  stimulus  took  place 
in  the  peripheral  organ. 

When  a  bow  is  drawn  against  the  edge  of  a  plate  the  ^^b^ations  aflfect  different 
parts  of  the  plate  unequally,  so  that  lycopodium  powder  sprinkled  on  such  a 
plate  assumes  a  complicated  pattern.  Waller  suggests  that  the  basilar  mem- 
brane vibrates  as  a  whole  to  every  tone,  but  that  it  presents  nodal  and  inter- 
nodal  jK)ints,  Uke  the  vibrating  plate.  Since  the  hair-cells  move  with  the  basilar 
membrane  they  produce  what  may  be  called  '  pressiire  patterns  '  against 
the  membrana  tectoria,  so  that  different  combinations  of  nerve  fibres  are 
stimulated  according  to  the  pattern,  i.e.  according  to  the  shape  of  the  com- 
pound wave.  A  somewhat  similar  hj-pothesis  has  been  put  forward  by  Ewald, 
but  neither  of  these  theories  presents  any  advantages  over  the  resonator  theory 
of  Helniholtz,  nor  does  it  account  satisfactorily,  as  the  Helmholtz  theory  does, 
for  the  remarkable  powers  we  possess  of  analysing  all  kinds  of  complex  sounds. 
The  cochlea  becomes  more  elaborate  in  structure  as  we  ascend  the  animal  scale, 
and  there  is  no  doubt  that  this  elaboration  attains  its  greatest  height  in  man, 
who  possesses  greater  powers  of  analysing  sounds  than  are  possessed  by  any  other 
animal. 


SECTION  V 

VOICE  AND  SPEECH 

The  development  of  the  analytical  powers  of  the  auditory  appara- 
tus is  so  closely  connected  with  that  of  the  faculty  of  speech  that 
we  may  conveniently  deal  with  the  latter  at  this  point  rather  than 
relegate  it  to  a  chapter  on  special  muscular  mechanisms.  We  may 
deal  first  with  the  mechanism  of  production  of  voice,  which  man  shares 
with  many  other  animals,  before  discussing  the  mechanism  of  the 
wholly  human  faculty  of  speech. 

Voice  is  produced  in  the  larynx,  a  modified  portion  of  the  wind- 
pipe, by  the  vibrations  of  two  elastic  bands,  the  vocal  cords,  which 
are  set  into  action  by  an  expiratory  current  of  air  from  the  limgs. 
In  many  respects  the  larynx  resembles  a  reed  instrument,  in  which 
a  current  of  air  is  caused  to  vibrate  by  the  vibrations  of  an  elastic 
tongue.  Whereas,  however,  the  period  of  the  vibrations  in  such  an 
instrument,  and  therefore  the  note,  is  determined  by  the  length  of 
the  tube  which  is  attached  to  the  reed,  in  the  larynx  the  note  pro- 
duced by  the  blast  of  air  is  modified  partly  by  alterations  in  the  tension 
of  the  vocal  cord,  and  partly  by  varying  the  strength  of  the  blast  of 
air 

ANATOMICAL  MECHANISM  OF  THE  LARYNX.  The  essential 
framework  of  the  larynx  is  formed  by  four  cartilages,  viz.  the  cricoid, 
the  thyroid,  and  the  two  arytenoid  cartilages.  The  cricoid  cartilage, 
which  lies  immediately  over  the  uppermost  ring  of  the  trachea,  is 
shaped  like  a  signet  ring,  the  small  narrow  part  being  directly  forwards 
and  the  broad  plate  backwaids.  The  thyroid  cartilage  consists  of 
two  parts  or  alse,  joined  together  in  front  and  forming  the  prominence 
known  as  Adam's  apple  ;  behind,  it  presents  four  processes  or  cornua, 
the  superior  of  which  are  attached  by  ligaments  to  the  hyoid  bone, 
while  the  inferior  cornua  articulate  with  the  postero- lateral  portion  of 
the  cricoid  cartilage.  By  means  of  this  articulation  very  free  move- 
ment is  permitted  between  the  two  cartilages,  the  general  direction 
of  movement  being  one  of  rotation  of  the  cricoid  cartilage  on  the 
thyroid,  round  a  horizontal  axis  directly  through  the  two  articular 
surfaces  between  the  two  cartilages,  while  movements  of  the  thyroid 
Tipon  the  cricoid  are  also  possible  in  the  upward,  downward,  forward, 
and  backward  directions.     The  two  aiytenoid  cartilages  are  pyramidal 

578 


VOICE  AND  SPEECH 


579 


in  shape.  By  their  bases  they  articulate  at  some  distance  from  the 
middle  line  wnth  convex  articular  surfaces  situated  in  the  upper  margin 
of  the  plate  of  the  cricoid  cartilage.  The  anterior  angle  of  the  base  is 
the  vocal  process,  while  the  external  angle  is  the  muscular  process 
of  the  arytenoid.  The  crico-arytenoid 
joints  permit  of  two  kinds  of  move- 
ments of  the  arytenoid  cartilages,  viz. : 

(1)  Rotation  on  their  base  around 
their  vertical  long  axis,  so  that  the 
anterior  vocal  process  is  rotated  out- 
wards and  the  muscular  process  back- 
wards and  inwards  or  conversely. 

(2)  Sliding  movements  of  the  whole 
arvtenoid  cartilage  either  outwards  or 
inwards,  so  that  their  inner  margins 
may  be  drawn  apart  or  approximated. 

The  larynx  is  covered  internally  by 
a  mucous  membrane  continuous  with 
that  of  the  trachea.  It  is  lined  with 
ciliated  epithelium,  except  over  the 
vocal  cords,  where  the  epithelium  is 
stratified.  The  two  vocal  cords,  or 
th^TO- arytenoid  ligaments,  consist  of 
elastic  fibres  which  run  from  the  middle 
of  the  inner  angle  of  the  thyroid  carti- 
lage to  be  inserted  into  the  anterior 
angle  of  the  ar}i:enoid  cartilages.  Their 
length  in  man  is  about  15  mm.,  in 
woman  about  11  mm.  The  cleft  be- 
tween them  is  known  as  the  glottis,  or 
rima  glottidis. 

Two  ridges  of  mucous  membrane 
above  and  parallel  to  the  v^ocai 
cords  are  the  false  vocal  cords  (Fig.  251).  Between  the  true  and 
the  false  vocal  cords  on  each  side  is  a  recess  known  as  the  ven- 
tricle of  Morgagni.  This  ventricle  permits  the  free  vibration  of 
the  vocal  cords.  The  false  cords  take  no  part  in  phonation.  but 
help  to  keep  the  true  cords  moistened  by  the  secretion  of  the 
numerous  mucous  glands  with  which  they  are  provided.  The  posi- 
tion and  tension  of  the  vocal  cords  is  determined  by  the  action  of  the 
various  intrinsic  muscles  of  the  larynx.  The  part  taken  by  the  various 
muscles  in  each  movement  cannot  be  directly  ascertained.  We  can 
in  most  cases  only  study  the  direction  of  the  fibres,  and  judge,  from 
this  direction  and  consequent  isolated  action  of  the  muscles,  the  part 


Fig.  2.51.  Anterior  half  of  the 
larjTix,  .seen  from  behind.  The 
section  on  the  right  .side  Ls 
somewhat  in  front  of  the  left 
side. 

e,  epiglottis;  e',  cushion  of 
epiglottis  ;  t,  thyroid  cartilage  ; 
•s.  s',  ventricle  of  larynx ;  h.  great 
cornii  of  hyoid  bone ;  /  a,  thyro- 
arytenoid muscle ;  v  I,  vocal 
cords.  Above  the  ventricles  are 
the  false  vocal  cords,  r,  first  ring 
of  trachea.    (A.  THOMSON'.) 


580 


PHYSIOLOGY 


taken  by  any  given  muscle  in  the  production  of  voice      The  chiet 
muscles  (Fig.  252)  are  as  follows  : 

(i)  The  crico-thyroid  muscle  is  a  short  triangular  muscle  attached 
below  to  the  cricoid  cartilage  and  above  to  the  inferior  border  of  the 
thvroid  cartilage  ;    the   fibres  pass  from  below  upwards  and  back- 


j^C-^^^..  IS. 


Fig.  252.     Muscles  of  tlie  larynx.     (Sappby.) 
A,  as  shown  in  a  view  of  the  larynx  from  the  right  side. 
1,  hyoid  bone  ;    2,  3,  its  comua  ;    4,  right ^la  of  thyroid  cartilage  ;    5,  posterior 
part  of  the  same  separated  by  oblique  line  from  anterior  part ;    6,  7,  superior  and 
inferior  tubercles  at  ends  of  oblique  line  ;   8,  upper  cornu  of  thyroid  ;   9,  thjoro-hyoid 
ligament  ;    10,  cartilago  triticea  ;    11,  lower  cornu  of  thyroid,  articulating  with  the 
cricoid  ;    12,  anterior  part  of  cricoid  ;    13,  crico-thyroid  membrane  ;    14,  crico-thyroid 
muscle;    15,  posterior  crico-arytenoid  muscle,  partly  hidden  by  thyroid  cartilage. 
B,  as  seen  in  a  view  of  the  larynx  from  behind. 
1,  posterior  crico-arytenoid  ;    2,  arjrtenoid  muscle  ;    3,  4,  oblique  fibres  passiaig 
around  the  edge  of  the  arytenoid  cartilage  to  join  the  thyro-arytcnoid,  and  to  fpi'm 
the  aryteno-epiglottic,  5. 


wards.  When  this  muscle  contracts,  the  cricoid  cartilage  is  drawn 
up  under  the  anterior  part  of  the  thyroid  cartilage  so  that  its  broad 
expansion  behind,  with  the  arytenoid  cartilages,  is  drawn  downwards 
and  backwards,  thus  putting  the  vocal  cords  on  the  stretch.  This 
muscle  is  probably  the  most  important  in  determining  the  tension  of 
the  vocal  cord.  N 

(2)  The  'posterior  crico-arytenoid  muscle  arises  from  a  broad  depres- 
sion on  the  corresponding  half  of  the  posterior  surface  of  the  cricoid 
cartilage.  Tt  passes  upwards  and  outwards,  its  fibres  converging,  to 
be  inserted  into   the   outer  angle  of  the  arytenoid  cartilage.     These 


VOICE  AND  SPEECH  581 

muscles  rotate  the  outer  angle  of  the  arytenoid  cartilages  backwards 
and  inwards.  They  thus  cause  a  movement  outwards  of  the  anterior 
angles,  so  that  the  glottis  is  widened.  During  every  act  of  expiration 
there  is  a  widening  of  the  glottis,  which  is  probably  effected  by  con- 
traction of  these  muscles.  If  they  are  paralysed,  the  vocal  cords  are 
approximated  and  tend  to  come  together  during  inspiration,  so  that 
dyspnoea  may  be  produced. 

(3)  The  lateral  (yrico^arytemid  muscle  arises  from  the  upper  border 
of  the  cricoid  cartilage  and  passes  backwards  to  be  inserted  into  the 
muscular  process  of  the  arytenoid  cartilage.  These  muscles  when 
they  contract  pull  the  muscular  process  of  the  arytenoid  cartilage  for- 
wards and  downwards,  thus  approximating  the  vocal  cords  at  their 
posterior  ends  and  antagonising  the  action  of  the  posterior  crico- 
arytenoid muscles. 

(4)  The  arytenoid  muscles  consist  of  transverse  fibres,  some  of 
which  decussate,  uniting  the  posterior  surface  of  the  two  arytenoid 
cartilages.  "When  they  contract  they  draw  the  arytenoid  cartilages 
together, 

(5)  The  thyro-arytenoid  muscles  consist  of  two  portions.  The 
outer  fibres  rise  in  front  from  the  thyroid  cartilage  and  pass  back- 
wards to  be  inserted  into  the  lateral  border  and  the  muscular  process 
of  the  arytenoid  cartilage.  Some  of  the  fibres  pass  obliquely  up- 
wards towards  the  aryteno-epiglottidean  folds.  These  are  often 
spoken  of  as  a  separate  muscle,  the  tkyro-epiglottidean.  By  their 
action  they  tend  to  draw  the  arytenoid  cartilages  forwards  and  to 
relax  the  vocal  cords.  The  upper  fibres  may  also  assist  in  depressing 
the  epiglottis.  The  inner  fibres  are  called  the  nmsculus  vocalis.  They 
arise  from  the  lower  half  of  the  angle  of  the  thyroid  cartilage,  and 
passing  backwards  in  the  vocal  cords  are  attached  to  the  vocal  pro- 
cesses and  to  the  adjacent  parts  of  the  outer  surfaces  of  the  ar}i;enoid 
cartilages.  Many  fibres  do  not  run  the  whole  distance,  but  end  in 
an  attachment  to  some  part  of  the  vocal  cord.  Although  their  action 
must  be  to  draw  the  arytenoid  cartilages  forwards,  yet,  since  they 
arc  contained  in  the  vibrating  portion  of  the  vocal  cords,  they  cannot 
by  their  contraction  relax  these  cords.  It  is  probable  that  they 
play  a  gi'eat  part  in  determining  the  tension  of  the  vocal  cords  after 
these  have  been  put  on  the  stretch  by  the  action  of  the  crico-thyroid 
muscles.  The}'  may  possibly  act  as  a  sort  of  fine  adjustment  of  the 
tension,  the  coarse  adjustment  being  represented  by  the  crico-thyniids. 

THE  PRODUCTION   OF  VOICE 
In  order  to  study  the  changes  in  the  larynx  which  are  a.ssociatetl 
with  voice  production  we  must  make  use  of  the  laryiiuoscopc.      The 
principle  of  this  instrument  is  very  simple.     A  large  concave  mirror 


582  PHYSIOLOGY 

with  a  central  aperture  is  fixed  before  one  eye  of  the  observer,  sitting 
in  front  of  the  patient  or  person  to  be  observed.  The  latter  is  directed 
to  throw  his  head  slightly  backwards  and  to  open  his  mouth.  In 
order  to  keep  the  tongue  out  of  the  way  the  patient  is  made  to  hold 
the  end  of  it  by  means  of  a  towel.  The  mirror  is  then  so  arranged 
as  to  reflect  light  from  a  lamp  into  the  cavity  of  the  mouth.  A  small 
mirror  fixed  in  a  handle  is  then  warmed,  so  as  to  prevent  the  con- 
densation of  the  patient's  breath,  and  passed  to  the  back  of  the  mouth 
until  it  rests  upon  and  slightly  raises  the  base  of  the  uvula.  By  this 
mirror  the  hght  reflected  into  the  mouth  from  the  large  mirror  is  again 
reflected  down  on  to  the  larynx,  and  a  reflection  of  the  larynx  and 
trachea  is  seen  in  the  mirror.  By  laryngoscopic  examination  we  can 
see  the  base  of  the  tongue,  behind  which  is  the  outline  of  the  epi- 
glottis. Behind  this  again  in  the  middle  line  are  seen  the  two  vocal 
cords,  white  and  shining  (Fig.  253).  The  cords  appear  to  approximate 
posteriorly  ;  between  them  is  a  narrow  chink,  the  diameter  of  which 
varies  with  each  respiration,  being  wider  during  inspiration.  On  each 
side  of  the  true  vocal  cords  are  seen  the  pink  false  vocal  cords.  In  some 
cases  the  rings  of  the  trachea,  and  even  the  bifurcation  of  the  trachea 
itself  (Fig.  253,  c),  may  be  seen  in  the  interval  between  the  vocal  cords. 

In  order  that  the  vocal  cords  may  be  set  into  vibration,  they 
must  be  put  into  a  state  of  tension  and  the  aperture  of  the  glottis 
narrowed,  so  as  to  afford  resistance  to  the  current  of  air.  In  the  dead 
larynx  it  is  possible  to  produce  sounds  by  forcing  air  from  bellows 
through  the  trachea,  after  the  vocal  cords  have  been  put  on  the 
stretch  by  pulling  the  arytenoid  cartilages  backwards.  By  experi- 
menting on  patients  on  whom  tracheotomy  has  been  performed,  it 
has  been  found  that  the  pressure  of  air  in  the  trachea,  necessary  to 
cause  production  of  voice,  is,  for  a  tone  of  ordinary  loudness  and 
pitch,  between  140  and  240  mm.  of  water,  and  with  loud  shouting  the 
pressure  rises  to  as  much  as  945  mm.  of  water.  This  pressure  is 
furnished  by  the  contraction  of  the  expiratory  muscles,  i.e.  of  the 
abdomen  and  of  the  thorax.  Since  the  pitch  of  the  note  produced 
rises  with  increasing  force  of  the  blast,  while  the  tension  of  the  cords 
remains  constant,  it  is  evident  that,  in  the  act  of  '  swelling  '  on  a 
note,  the  increased  pressure  necessary  for  the  crescendo  must  be 
associated  with  diminishing  tension  of  the  cords.  It  is  the  failure  to 
secure  this  muscular  relaxation  that  so  often  causes  a  singer  to  sing 
sharp  when  swelling  on  any  given  note. 

The  voice,  like  the  sound  produced  on  any  musical  instrument, 
may  vary  either  in  pitch,  loudness,  or  in  ({uality  or  timbre.  The 
range  of  any  individual  voice  is  generally  about  two  octaves.  The 
pitch  of  the  voice  usually  employed  is  determined  chiefly  by  the  length 
of  the  vocal  cords.    Thus  in  children  the  voice  is  high-pitched.    Before 


VOICE  AND  SPEECH 


583 


and  at  puberty  there  is  a  considerable  development  in  tne  size  of 
the  larynx  in  both  sexes.  This  is  especially  marked  in  the  male,  and 
accounts  for  the  sudden  drop  in  pitch  ('  breaking  ')  of  the  voice.     In 


¥ia.  253.  Three  laryngustupiu  views  of  the  .superior  aperture  of  the 
laryux  and  surrounding  parts  in  different  states  of  the  glottis  during 
life.  (FroraCzEUMAK.) 
A,  the  glottis  during  the  emission  of  a  higli  note  in  singing.  B,  in  easy 
or  quiet  inhalation  of  air.  C,  in  the  state  of  widest  possible  dilatation,  as 
in  inhaling  a  very  deep  breath.  The  diagrams  A',  B',  C"  have  been  added 
to  Czermak's  figures  to  show  in  horizontal  seetions  of  the  glottis  the  posi- 
tion of  the  voeal  ligauuMits  and  arytenoid  cartilages  in  the  three  several 
states  represented Jn  the  other  figures.  In  all  the  figures  so  far  as  nuirked, 
the  letters  indieate  the  parts  as  follows,  viz.  :  /,  the  base  of  the  tongue  ; 
e,  the  upjjer  free  part  of  the  epiglottis  ;  e',  the  tuberele  or  cushion  of  the 
epiglottis  ;  /;  /(,  part  of  the  anterior  wall  of  the  pharynx  behind  the  larynx; 
in  the  nuirgin  of  tiie  aryteno-epiglottidean  fokl  w,  the  swelling  of  the  mem- 
brane caused  by  the  eimciform  cartilage  ;  *■,  that  of  tiie  corniculum  ;  n.  the 
tip  of  the  arj'tenoid  cartilages ;  c  r.  the  true  vocal  cords  or  lips  of  the  rinui 
glottidis  ;  c  v  .y.  the  superior  or  false  vocal  cords  ;  bclwccn  tliem  the  ven- 
tricle of  the  larynx;  in  (\  /  r  is  placed  cm  the  anterior  wall  of  (lie  receding 
trachea,  and  h  indicates  the  commencement  of  the  two  bronihi  beyond  the 
bifurcation,  which  nuvy  be  brought  into  view  in  this  state  of  extreme 
dilatation. 


the  female  the  increased  size  of  the  larynx  is  chiefly  {)erceptible  in  the 
increase  in  fulness  and  richness  of  the  voice  which  occurs  at  this  age. 
Even  when  we  take  all  the  voices  together,  bass,  tenor,  alto,  and 
soprano,  the  total  range  for  ordinary  individuals  does  not  exceed  three 
octaves.  In  singing  the  voice  may  be  produced  in  various  ways,  i.e.  in 
different  registers.     Thus  we  distinuuish  the  chest  register,  the  middle 


584  PHYSIOLOGY 

register,  and  the  head  register.  The  deeper  notes  of  any  individual 
voice  are  always  produced  in  the  chest  register.  Observation  of  the 
vocal  cords  shows  that  when  producing  such  notes  the  glottis  forms 
an  elongated  slit,  all  the  muscles  which  close  the  glottis  and  increase 
the  tension  of  the  cords  being  in  action.  The  vocal  cords  are  relatively 
thick  and  broad  and  can  be  seen  to  vibrate  over  their  whole  extent. 
When  singing  with  the  head  voice  the  vibrations  of  the  cord  are 
apparently  confined  to  their  inner  margins ;  the  aperture  of  the 
glottis  is  wider  in  front  than  behind,  so  that  more  air  escapes  during 
phonation  by  this  method  than  in  the  production  of  the  chest  voice. 

In  order  to  change  the  pitch  of  the  note  the  following  means  are 
probably  employed  in  the  larynx  : 

(1)  Alteration  in  the  tension  of  the  vocal  cords. 

(2)  Alteration  in  the  length  of  the  part  of  the  vocal  cords  which 
is  free  to  vibrate,  which  can  be  accomplished  by  the  approximation 
of  the  arytenoid  cartilages  to  one  another,  or  by  their  approximation 
to  the  thyroid  cartilage. 

(3)  The  alteration  in  the  shape  of  the  vocal  cords,  which  is  deter- 
mined by  the  activity  of  the  different  portions  of  the  internal  thyro- 
arytenoid muscles. 

(4)  The  varying  pressure  of  the  blast  of  air  passing  through  the 
glottis. 

The  loudness  of  the  tone  produced  is  practically  proportional 
to  the  force  of  the  blast  of  air  employed.  The  quality  or  timbre 
of  the  voice  depends  not  so  much  on  the  vocal  cords  as  on  the  accessory 
resonating  apparatus,  represented  by  the  trachea  and  chest  and  by 
the  cavity  of  the  mouth.  The  greater  part  of  the  education  involved 
m  voice  training  is  directed  to  the  modification  of  the  shape  of  the 
mouth  cavity,  so  as  to  secure  the  greatest  possible  fulness,  i.e.  richness 
in  overtones,  of  the  tone  produced  in  the  larynx. 

THE  MECHANISM  OF  SPEECH 

The  sounds  employed  in  speech,  viz.  vowels  and  consonants,  are 
produced  by  modifying  the  laryngeal  tones  by  changes  in  the  shape  of 
the  mouth  and  nasal  cavities.  In  whispering  speech  there  is  no 
phonation  at  all,  but  the  sound  is  produced  by  the  issue  of  a  blast  of 
air  through  a  narrow  opening  between  the  lips,  between  the  tongue  and 
soft  palate,  or  between  the  tongue  and  the  teeth. 

The  vowel  sounds  are  continuous,  whereas  the  consonants  are 
produced  by  interruptions,  more  or  less  complete,  of  the  outflowing 
air  in  different  situations.  The  vowel  sounds,  u,  o,  a,  e,  i  (pronounced 
oo,  oh,  ah,  eh,  ee),  are  tones,  i.e.  are  produced  by  a  regular  series  of 
vibrations.  These  tones  take  their  origin  in  the  mouth  cavity,  as 
can  be  shown  easily  by  the  fact  that  we  can  whisper  these  sounds 


VOICE  AND  SPEECH  585 

distinctly  without  any  phonation  whatever.  To  each  of  them  corre- 
sponds one  or  two  distinct  notes,  the  pitch,  i.e.  the  resonance,  of  which 
is  regulated  by  the  shape  of  the  cavity  in  which  they  are  produced. 
It  is  possible  to  determine  these  notes  by  means  of  res  .nators.  The 
pronunciation  even  of  the  simplest  vowel  sounds  differs  in  different 
individuals.  For  instance,  those  pronounced  by  a  Londoner  differ 
from  those  pronounced  by  a  man  from  Manchester  or  from  Yorkshire, 
and  the  French  \  owels  differ  somewhat  in  pitch  from  those  employed 


A  {ah)  U  {ooj  I  (ce) 

Flu.  254.     Shaix;  of  the  oral  cavity  in  the  production  of  the  vowel  sounds,  A,  U,  I. 

(GBtJTZXER.) 

by  the  German,  and  these  again  from  those  employed  by  the  average 
Englishman. 

The  characteristic  notes  were  given  by  Helmholtz  as  follows  : 


If  the  five  vowels  are  whispered  loudly,  the  gradual  rise  in  pitch 
of  the  tone  is  easily  perceptible.  We  do  not  in  this  way,  however, 
note  the  lower  component  of  the  soimd  in  the  E  and  I ;  this  can  be 
brou2;ht  out  by  a  simple  device  (Fig.  254).  If  we  place  the  mouth  in  the 
position  necessary  to  produce  these  different  vowels,  and  then  })ercuss 
over  the  cheek,  we  obtain  the  typical  note  for  each  vowel,  the  air  in 
the  mouth  cavity  being  set  into  vibration  by  the  percussion.  Now 
shift  the  finger,  which  is  to  be  percu.ssed,  so  that  it  lies  over  the  pharynx, 
just  behind  the  angle  of  the  jaw,  and  percuss  again.  The  note  will 
be  observed  to  rise  with  U,  0,  A,  and  then  fall  with  E,  I.  With  the 
three  vowels  U,  0,  A,  we  have  a  single  cavity  formed  by  the  lips, 
the  ])alate,  and  the  tongue  ;  this  cavity  is  lousiest  and  narrowest  with 
U  and  shortest  and  most  open  with  A.     With  E  and  1  the  dorsum 


586  PHYSIOLOGY 

of  the  tongue  comes  up  against  the  front  part  of  the  soft  palate,  so 
that  the  mouth  cavity  is  divided  into  two,  the  anterior  short  narrow 
cavity,  and  the  posterior  broader  cavity  between  the  soft  palate  and 
the  base  of  the  tongue.  We  therefore  have  two  notes  produced, 
one  in  each  cavity.  The  change  in  shape  of  the  mouth  cavity  is  shown 
in  the  figures.  With  U  and  A  the  cavity  seems  to  be  single ;  with  I 
the  development  of  a  pharyngeal  resonating  cavity  is  well  shown. 
Diphthongs  are  produced  by  changing  the  form  of  the  mouth  cavity 
from  that  of  one  vowel  sound  to  another,  thus  AI  (the  English  i)  = 
ah-ee  run  together  and  abbreviated. 

Consonants  are  sounds  produced  by  a  sudden  check  being  placed 
in  the  course  of  the  expiratory  blast  of  air  by  closure  of  some  part 
of  the  pharynx  or  mouth.  They  are  classified  into  labials,  dentals, 
or  gutturals,  according  as  the  check  takes  place  at  the  lips,  between 
teeth  and  tongue,  or  between  back  of  tongue  and  soft  |,rJate.  Each 
of  these  again  can  be  divided  into  soft  and  hard  consonants  as  they 
are  accompanied  or  not  with  phonation.  Thus  when  we  pronounce 
D  the  production  of  the  laryngeal  sound  goes  on  during  the  check 
of  the  sound  produced  at  the  teeth,  whereas  with  T  there  is  an  absolute 
interruption  of  phonation  during  the  pronunciation  of  the  consonant. 
It  is  thus  practically  impossible  to  make  any  marked  difference 
between  hard  and  soft  consonants  when  whispering. 

In  the  production  of  nasal  sounds  such  as  NG  the  mechanism 
is  the  same  as  for  the  production  of  B,  D,  G,  except  that  the  posterioi' 
opening  of  the  nares  is  not  kept  shut  by  the  soft  palate,  so  that  part 
of  the  sound  comes  continually  through  the  nasal  passages,  when  it 
acquires  a  peculiar  resonance.  These  sounds  are  on  this  account  often 
spoken  of  as  '  resonants.'  The  aspirates  are  produced  by  the  passage 
of  a  simple  blast  of  air  through  a  narrow  opening  which  may  be  at 
the  throat  as  in  H,  between  tongue  and  teeth  as  in  TH,  or  between 
lips  and  teeth  as  in  PH  oi"  F. 

The  vibratives,  such  as  R,  are  formed  by  placing  the  tip  of  the 
tongue  or  the  uvula,  or  the  lips,  in  the  path  of  the  blast  of  air  so  that 
they  are  set  into  vibration  by  the  blast.  In  English  the  vibrative  R 
employed  is  entirely  due  to  the  tongue. 

The  sibilants,  which  may  be  voiceless  as  in  '  S '  or  accompanied 
with  phonation  as  in  '  Z,'  consist  of  continuous  noises  produced  by 
a  narrowing  of  the  path  of  the  air  between  the  tongue  and  the  hard 
palate.  They  are  therefore  similar  in  production  to  the  aspirates. 
In  the  production  of  the  sound  '  L  '  the  tongue  is  applied  by  its  edge  to 
the  alveolar  process  of  the  upper  jaw,  so  that  the  air  or  voice  escapes 
by  two  small  apertures  in  the  region  of  the  first  molar  and  between 
the  inner  side  of  the  cheek  and  the  teeth.  The  acoustic  characters 
of  these  various  consonants  are  still  but  imperfectly  studied. 


V1SI#N 

SECTION  VI 

DIOPTRIC  MECHANISMS  OF  THE  EYEBALL 

When  light  falls  on  any  object  a  certain  proportion  of  it  is  reflected 
and  scattered,  and  will  affect  any  organism  in  the  neighbourhood 
possessing  sensibility  to  light.  Mere  sensibility  of  the  surface  to  light 
would  not,  however,  suffice  to  arouse  projected  sensations,  since  the 
rays  of  light  from  a  number  of  different  objects  would  interfere 
with  one  another.  An  animal  with  such  sensibility  would  be 
aware  of  or  be  able  to  react  to  differences  of  light  and  darkness,  but 
could  not  direct  its  movements  in  accordance  with  the  nature  of  the 
objects  from  which  the  light  proceeded.  For  this  purpose  there 
must  be  not  only  a  sm-face  sensitive  to  light  impressions  but 
also  dioptric  mechanisms,  by  means  of  which  a  real  image  of  external 
objects,  in  their  proper  spatial  relationships,  is  thrown  on  to 
an  extended  sensory  surface.  Each  point  in  this  surface  will 
correspond  to  a  point  lying  outside  the  body  and  serving  as  a  source 
of  light,  and  the  sensations  evoked,  since  they  correspond  to  the  rays 
of  light  coming  from  external  objects,  can  be  projected,  and  referred 
to  the  objects  themselves  lying  outside  and  at  some  distance  from 
the  body. 

The  organ  of  vision,  the  eye,  consists  of  two  parts,  viz.  : 

(a)  The  sensory  surface  or  retina,  composed  of  a  number  of  areas, 
each  of  which  can  be  separately  stimulated  by  light. 

(&)  A  dioptric  mechanism  for  projecting  a  real  image  of  external 
objects  on  this  sensory  surface. 

We  have  in  fact  an  arrangement  very  analogous  to  a  photo- 
graphic camera,  where  a  real  image  is  thrown  by  a  lens  on  to  a  sensitive 
plate,  each  point  of  which  undergoes  chemical  change  in  proportion 
to  the  amount  of  incident  light,  so  that  a  photographic  record  is  the 
result. 

THE  FORMATION  OF   AN  IMAGE   BY   A  LENS 
We  may  confine  our  attention  to  the  case  of  a   bi-convex  lens, 
and  we  may  assume  in  the  first  place  that  the  thickness  of  the  lens  is 
negligible.     In   Fig.  255  c  and  c'  are  the  centres  of  the   spherical 

687 


588 


PHYSIOLOGY 


surface  bounding  the  lens  ;  the  line  joining  them  is  the  optical  axis  of 
the  lens.  The  surface  at  q  is  parallel  to  the  surface  at  r,  so  that  a 
ray  of  light,  such  as  p  q  falling  on  the  lens  at  q,  \\'ill  leave  the  lens  at 
R  in  direction  rs  parallel  to  pq.  The  point  o  where  the  ray  cuts  the 
p 


Fig.  255. 


optical  axis  is  known  as  the  optical  centre  of  the  lens.  This  optical 
centre  in  a  bi-convex  lens  lies  within  the  lens,  its  distance  from  the 
two  surfaces  being  practically  as  their  radii. 

Since  we  are  neglecting  the  thickness  of  the  lens  the  line  pqrs 


Fig.  256.     Diagram  of  the  course  of  parallel  rays  through  a  biconvex  lens 
by  which  they  are  converged  to  the  principal  focus,  r. 


Fig.  257.      The  rays  of  ligiil  from  a  converge  oji  pussmg  througli  the  lens 
to  the  secondary  focus,  y.     F  and  a  are  conjugate  foci. 

may  be  regarded  as  straight,  so  that  we  may  say  that  the  rays  which 
pass  through  the  centre  of  a  lens  do  not  deviate.  If  a  pencil  of  parallel 
rays  falls  upon  the  lens,  while  those  rays  which  pass  through  the  optic 
centre  undergo  no  deviation,  all  the  others  on  leaving  the  lens  will 
be  convergent  towards  a  point  which  is  known  as  the  principal  focus  of 
the  lens  (Fig.  256).     Conversely,  if  a  point  of  light  be  placed  at  the 


DIOPTRIC  MECHANISMS  OF  THE  EYEBALL 


589 


principal  focus  the  rays  of  light  passing  through  it  to  the  lens  will  take 
the  reverse  course  and  leave  the  lens  as  a  bundle  of  parallel  rays.  Any 
point  of  light  situated  between  infinite  distance  and  the  principal 
focus  will  have  a  corresponding  point  on  the  other  side  of  the  lens  to 
which  its  rays  will  converge.  Such  corresponding  points  are  known  as  a 
nonjwjate  foci  (Fig.  257).  In  a  thin  lens,  with  the  same  media  on 
each  side,  the  anterior  and  posterior  focal  distances  are  the  same,  so 
that  from  whichever  direction  a  parallel  beam  falls  on  the  lens  the  point 
to  which  its  rays  are  converged  on  the  other  side  of  the  lens  is  constant. 
If  instead  of  a  point  of  light  we  have  a  series  of  points  such  as 
that  coming  from  a  bright  line  in  the  plane  of  the  paper  (as  in  Fig.  258), 


Fig,  258. 


each  of  these  points  will  have  a  corresponding  point  on  the  opposite 
side  of  the  lens.     Thus  from  the  point  p  three  rays  may  be  taken,  viz.  : 

(1)  The  ray  po,  which  passes  through  the  centre  of  the  lens  and  does 
not  deviate. 

(2)  The  ray  pe,  which  is  parallel  to  the  axis  and  therefore  is 
converged  to  the  principal  focus  02* 

(3)  The  ray  pg,  which  passes  through  the  focus  on  the  front 
surface  of  the  lens  0^  and  therefore  takes  a  course  on  the  other  side  of 
the  lens  parallel  to  the  axis.  The  intersection  of  any  two  of  these  three 
lines  will  be  the  situation  ot  the  image  p  to  the  point  p.  In  the  same 
way  all  the  other  points  in  the  object  will  have  a  corresponding  image 
on  the  opposite  side,  so  that  an  inverted  real  image  of  the  luminous 
object  is  formed  on  this  side. 

The  size  of  the  image  as  compared  with  the  object  will  depend  on 
the  distance  of  the  object  from  the  lens.  It  is  greater  than  the  object 
if  the  latter  is  less  than  2/  (twice  the  focal  distance)  from  the  len.'^, 
ecjual  if  the  distance  is  2/,  and  diminished  if  the  distance  is  greater 
than  2/. 


590  PHYSIOLOGY 

A  lens  with  a  focal  distance  of  1  metre  is  taken  as  unit  strength 
Such  a  lens  is  said  to  have  a  strength  of  one  dioptre  ;  a  lens  of  two 
dioptres  would  have  a  focal  distance  of  I  metre  ;  of  four  dioptres  one 
of  -|-  metre,  and  so  on. 

DIOPTRIC  MECHANISMS  OF  THE  EYEBALL 
The  eye  is  not  directly  comparable  to  a  camera  in  its  optical 
arrangements,  since  the  image  is  formed,  not  in  air,  but  in  the  fluids 
of  the  eye  itself.  Moreover  the  conditions  are  complicated  by  the 
facts  that  it  is  impossible  to  neglect  the  thickness  of  the  refractive 
media,  and  that  these  are  many  in  number. 

If  we  take  the  simplest  case,  where  there  are  only  two  media  separated  from 

A  E  C 


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s 

Q 


B 


D 


Fig.  259. 


one  another  by  a  spherical  surface  of  contact,  we  can  easily  determine  the 
course  taken  by  any  ray  in  passing  from  the  first  to  the  second  medium. 

In  Fig.  2.59  (from  Landois)  let  L  be  the  first  {e.g.  air)  and  G  the  second  {e.g. 
glass).  These  are  separated  by  the  spherical  surface  ab,  with  its  centre  at  m. 
Since  all  the  radii  drawn  from  m  to  ab  are  perpendicular  to  the  surface  all  rays 
falling  in  the  direction  of  the  radii  must  pass  unrefracted  through  m.  All  rays  of 
this  sort  are  called  rays  or  lines  of  direction ;  m,  as  the  point  of  intersection  of 
all  these,  is  called  the  nodal  point.  The  line  which  connects  m  with  the  vertex 
of  the  spherical  surface,  x,  and  which  is  prolonged  in  both  directions,  is 
the  optic  axis,  OQ.  A  plane  (ef)  in  x,  perpendicular  to  OQ,  is  called  the 
principal  plane,  and  in  it  x  is  the  principal  point.  The  following  facts  have  been 
ascertained  :  ( 1 )  All  rays  (a  to  a^),  which  in  the  first  medium  are  parallel  with  each 
other  and  with  the  optic  axis,  and  fall  upon  ab,  are  so  refracted  in  the  second 
medium  that  they  are  all  again  united  in  one  point  {pi)  of  the  second  medium. 
This  is  called  the  second  principal  focus.  A  plane  in  this  point,  perpendicular  to 
oQ,  is  called  the  second  focal  plane  (CD).  (2)  All  rays  {c  to  Cg),  which  in  the 
first  medium  are  parallel  to  each  other,  but  not  parallel  to  OQ,  reunite  in  a  point 
of  the  second  focal  plane  (r),  where  the  non-refracted  directive  ray  (c^wr)  meets 
this.  (In  this  case  the  angle  formed  by  the  rays  c  to  C2  with  cq  must  be  very 
small.)  The  propositions  1  and  2,  of  course,  may  be  reversed  ;  the  divergent  rays 
proceeding  from  p  towards  ab  pass  into  the  first  medium  parallel  to  each  other, 


DIOPTRIC  MECHANISMS  OF  TITE  EYEBALL 


591 


and  also  with  the  axis  CQ  (a  to  0^)  ;  and  the  rays  proceeding  from  r  pass  into 
the  first  medium  parallel  to  each  other,  Init  not  jiarallel  to  the  axis  OQ  (as  c  to 
C2).  (3)  All  rays,  which  in  the  second  medium  are  parallel  to  each  other  (6  to  65) 
and  with  the  axis  OQ,  reunite  in  a  point  in  the  first  medium  (p)  called  the  first 
focal  point  ;  of  course,  the  converse  of  this  is  true.  A  plane  in  this  point  perpendi- 
cular to  (jg  is  called  the  first  focal  plane  (ab).  The  radius  of  the  refractive 
svirface  (mx)  is  equal  to  the  difference  of  the  distance  of  both  focal  points  {p  and 
Pi)  from  the  principal  focus  (x)  ;  thus  mx  =  p^x  -  px. 

In  compound  systems  composed  of  several  refractive  media  with  spherical 
surfaces  of  contact,  such  as  the  eye,  we  may  proceed  from  medium  to  medium 
with  the  same  methods  as  those  just  described.  Since,  however,  such  a  procedure 
would  be  very  tedious,  the  method  first  ]jropo!-ed  by  Gauss  is  usually  adopted. 
Gauss  showed  that  if  the  several  media  are  '  centred  ' — i.e.  if  all  have  the  same 
optic  axis— then  the  refractive  indices  of  such  a  centred  system  may  be  repre- 


Fio,  260.  The  position  of  the  cardinal  point-,  in  thi     i  lu  in  it  h  c  u     (Helmholtz.) 
h,,  h,^,  principal  points  ;   l\,  k,,,  nodal  points  ;   F  ,  posterior  focus. 


seated  by  two  equally  strong  refractive  surfaces  at  a  certain  distance  apart. 
The  rays  falling  upon  the  first  surface  are  not  refracted  from  it,  but  are  regarded 
as  projected  forwards  parallel  with  themselves  to  the  second  surface.  Refrac- 
tion is  then  considered  to  take  place  at  the  second  surface  just  as  if  that  were 
the  only  surface  present  (represented  by  the  dotted  line  U  in  Fig.  260). 

All  such  systems  possess  three  pairs  of  cardinal  points,  viz.  two 
principal  foci,  two  principal  points,  and  two  nodal  points.  These  points 
may  be  defined  by  the  following!;  principles  : 

{a)  Rays  which  pass  through  the  principal  focus  are.  after  refrac- 
tion, parallel  to  the  optic  axis. 

(6)  Rays  which  pass  throuyh  the  first  principal  point,  after  refrac- 
tion, pass  through  the  second. 

(c)  Rays  which  pass  through  the  first  nodal  point,  after  refraction, 
pass  through  the  second,  and  the  direction  of  the  refracted  ray  is 
parallel  to  the  direction  of  the  incident  ray. 

In  Fig.  2W  the  situation  of  the.so  cardinal  [loints  is  shown  in  the 


592 


PHYSIOLOGY 


human  eye.  The  rays  of  light  pass  through  the  following  media, 
cornea,  aqueous  humour,  lens,  and  vitreous  humour,  and  may  be 
refracted  at  the  following  surfaces ;  anterior  and  posterior  surfaces  of 
the  cornea,  anterior  and  posterior  surfaces  of  the  lens.  Since,  however, 
the  refractive  indices  of  cornea,  aqueous  humour,  and  vitreous  humour 
are  practically  identical,  we  can  reduce  the  refractive  media  to  two, 
viz.  cornea,  aqueous,  and  vitreous  in  the  one  case,  and  lens  in  the  other  ; 
and  the  refractive  surfaces  to  three,  viz.  anterior  surface  of  cornea, 
anterior  surface  of  lens,  and  posterior  siu^face  of  lens. 

In  order  to  determine  the  path  of  the  rays  in  the  eye  we  have  to 
determine  the  following  data.  viz.  : 

(1)  The  radius  of  curvature  of  the  anterior  surface  of  the  cornea. 

(2)  The  distance  of  the  anterior  surface  of  the  cornea  from  the 
anterior  surface  of  the  lens. 

(3)  The  radius  of  curvature  of  the  anterior  surface  of  the  lens. 

(4)  The  thickness  of  the  lens. 

(5)  The  radius  of  curvature  of  the  posterior  surface  of  the  lens. 

In  addition  we  must  know  the  refractive  index  of  the  cornea  and 
aqueous  or  vitreous  humour,  and  also  the  average  refractive  index 
of  the  lens.  There  is  a  considerable  difference  between  the  refractive 
indices  of  the  outer  and  the  inner  portions  of  the  lens,  the  inner  part 
being  much  denser  and  having  a  higher  refractive  index  than  the 
periphery.  The  following  Table  represents  the  constants  of  a  human 
eve  as  determined  by  Hslmholtz  :  * 


Refractive  index  of  aqueous  and  vitreous  humours 
Total  refraction  index  of  lens       .... 

Radius  of  curvature  of  cornea      .... 
„  ,,  anterior  surface  of  lens 

„  „  posterior  surface  of  lens    . 

Distance  from  anterior  surface  of  cornea  to  anterior  surface  of 

lens 
„  „  „  posterior   surface 

of  lens     . 
Anterior  focus  of  cornea 
Posterior  focus  of  cornea 
Focus  of  lens 
Posterior  focus  of  eye  . 
Anterior  focus  of  eye  . 
Distance  from  anterior  surface  of 
First  principal  point 
Second  principal  point 
First  nodal  point 
Second  nodal  point 
Anterior  focus  of  eye 
Posterior  focus  of  eye 


cornea  to 


1-3365 

1-4371 
mm. 

8 
10 

6 

3-G 

7-2 
23-692 
31-692 
43-707 
19-875 
14-858 

1-9403 
2-3565 
6-957 
7-373 
-  12-918 
22-231 


*  Quoted  by  Tigerstedt. 


DIOPTRIC  MECHANISMS  OF  THE  EYEBALL  593 

It  will  be  seen  that  both  the  principal  points  lie  in  the  anterior 
chamber,  while  the  nodal  points  fall  in  the  back  part  of  the  lens.  The 
posterior  focus  of  the  eye  falls  upon  the  retina.  For  many  purposes 
we  may  simpUfy  our  calculations  by  running  the  principal  points 
and  nodal  points  together.  In  such  a  reduced  eye  the  single  principal 
point  is  situated  2-3  mm.  behind  the  anterior  surface  of  the  cornea,  and 
the  single  nodal  point  0-47  mm.  in  front  of  the  hinder  surface  of  the 
lens.  If  a  circle  be  drawn  from  the  single  nodal  point  as  a  centre 
through  the  single  principal  point  as  a  circumference  we  get  a  surface 
II  in  the  figure,  which  represents  the  anterior  refracting  surface 
of  such  a  reduced  eye. 

A  reference  to  the  Table  of  Constants  of  the  human  eye  shows 
that,  whereas  the  anterior  focal  distance  of  the  cornea  is  23  mm.,  that 
of  the  whole  eye  is  15  mm.  and  that  of  the  lens  44  mm.  It  is  evident 
from  this  that  the  anterior  surface  of  the  cornea  is  the  most  important 
refractive  surface  of  the  eye,  and  that,  in  the  convergence  of  rays 
necessary  for  the  formation  of  an  image  on  the  retina,  it  is  the  refrac- 
tion at  this  surface  which  plays  the  greatest  part.  Under  water  this 
refraction  is  of  course  abolished,,  since  the  refractive  indices  of  the 
aqueous  humour  and  cornea  are  practically  identical  with  that  of 
water.  The  eye  therefore  becomes  long-sighted ;  it  is  impossible 
to  get  any  clear  image  of  near  objects,  and  distant  objects  can  only  be 
seen  with  a  strong  effort  of  accommodation.  A  smaller  effect  is  pro- 
duced by  removal  of  the  lens,  an  operation  often  undertaken  when  this 
body  has  become  opaque  as  a  result  of  cataract.  Such  an  operation 
not  only  abolishes  the  power  of  accommodation  of  the  eye,  but  diminishes 
the  refractive  power  of  the  eye  at  rest  by  ten  dioptres,  so  that  a  lens 
of  this  power  has  to  be  placed  at  the  front  of  the  eye  in  order  to  render 
possible  clear  vision  of  distant  objects. 

PATH  OF  THE  RAYS  IN  THE  FORMATION  OF  THE 
RETINAL  IMAGE 

In  the  reduced  eye  the  construction  of  the  path  of  the  rays  is 
very  simple.  When  the  eye  is  focused  for  the  object  which  is  being 
looked  at,  the  rays  from  any  point  of  the  object  come  to  a  point  on  the 
retina.  All  that  is  necessary  therefore  is  to  draw  lines  from  points 
of  the  object  through  the  single  nodal  point  to  the  retina,  as  is  shown 
in  Fig.  261.  The  image  thus  produced,  like  that  produced  by  a 
bi-convex  lens,  is  real,  inverted,  and  diminished  in  size.  The  further 
the  distance  of  the  object  from  the  retina  the  smaller  will  be  its  image 
on  the  retina.  The  angle  formed  at  the  jimction  of  two  lines  drawn 
from  the  extreme  points  of  an  external  object  to  the  nodal  point  is  the 
*  visual  angle.' 

In  the  schematic  eye  a  visual  angle  of  sixty  seconds  corresponds 

38 


594  PHYSIOLOGY 

to  a  distance  on  the  retina  between  the  two  ends  of  the  image  of 
•00438  mm.  Few  people  can  distinguish  two  points  of  light  the 
line  joining  which  subtends  a  smaller  visual  angle  than  sixty  seconds. 
If  we  measure  the  histological  elements  in  the  centre  of  the  retina 
which  are  responsible  for  distinct  vision,  viz.  the  cones,  we  find  that 
in  the  yellow  spot  each  cone  is  about  -002  to  -005  mm.  thick.  The 
limits  of  our  power  of  distinguishing  two  luminous  points  is  approxi- 
mately in  agreement  with  the  diameter  of  each  end- organ  of  vision. 
In  order  that  the  images  of  the  two  points  may  give  rise  to  distinct 
sensations  their  images  must  fall  upon  different  cones.  This  fine- 
ness of  vision  exists  only  at  the  yellow  spot,  the  accuracy  of 
vision  in  the  peripheral  parts  of  the  retina  being  very  much  lower. 
Not  only  is  the  image  less  perfectly  focused,  but  the  number  of  sensory 


FiQ.  261.     Path  of  the  rays  in  the  formation  of  an  image  on  the  retina. 

elements  in  a  given  area  of  the  retina  diminishes  steadily  as  we  pass 
from  centre  to  periphery. 

OPTICAL  DEFECTS  OF  THE  EYE 
The  normal  eye  is  so  constructed  that  parallel  rays  come  to  a 
point  on  the  retina.    Kays  which  are  divergent  when  they  fall  on  the 
anterior  surface  of  the  cornea  are  brought  therefore  to  a  focus  behind 
the  retina. 

In  such  an  eye  any  object  lying  at  a  distance  nearer  than  five 
metres  would  give  rise  to  an  image  behind  the  retina,  were  it  not  for 
the  fact  that  the  eye  possesses  means  of  altering  its  focus  and  so  of 
bringing  divergent  rays  to  a  focus  on  the  retina  ;  this  means  is  known 
as  accommodation.  In  a  photographic  camera  the  process  of  focusing 
is  carried  out  by  altering  the  distance  between  the  lens  and  the  sensi- 
tive plate.  The  same  method  is  adopted  in  the  eyes  of  certain  animals. 
In  the  mammalian  eye,  however,  accommodation  for  near  objects,  i.e. 
the  focusing  of  divergent  rays  on  to  the  retina,  is  accomplished  by 
a  change  in  the  curvature  of  the  lens.  The  lens  becomes  more  convex 
on  its  anterior  surface,  so  that  its  refractive  power  is  increased  and  the 
hinder  focus  of  the  dioptric  mechanism  of  the  eye  is  therefore  diminished. 
Every  eye  possesses  a  certain  definite  range  of  vision,  which,  in   a 


DIOPTRIC  MECHANISMS  OF  THE  EYEBALL 


595 


normal  person,  has  its  far  point  at  infinite  distance  and  its  near  point 
at  a  distance  from  the  eye  which  depends  on  the  elasticity  of  the 
lens  and  the  range  through  which  this  can  alter  its  curvatm-e. 

The  normahty  of  an  eye  is  determined  by  the  fact  that  parallel 
rays  come  to  a  focus  on  the  retina  when  the  apparatus  of  accommoda- 
tion is  at  rest.  Two  classes  of  deviation  from  this  normal,  or  emme- 
tropic, eye  are  common.  In  the  first  class  parallel  rays  come  to  a 
focus  in  front  of  the  retina.  In  such  eyes,  which  are  designated 
myopic,  it  is  impossible  to  get  a  clear  image  on  the  retina  of  distant 
objects.  In  order  that  the  rays  may 
be  focused  on  the  retina  they  must  be 
divergent,  so  that  even  when  accom- 
modation is  paralysed  the  far  point 
of  distant  vision  lies  at  some  finite 
distance  from  the  eye,  varying  with 
the  extent  of  the  disorder.  If  in  such 
eyes  the  range  of  accommodation  is 
normal,  the  near  point  will  be  much 
nearer  to  the  eye  than  in  the  em- 
metropic eye  (Fig.  262). 

The  second  class  of  abnormal 
eyes  are  known  as  hypermetropic. 
These  eyes  can  be  regarded  as  too 
short  for  their  refractive  media. 
Parallel  rays  are  brought  to  a 
focus  at  a  point  behind  the  retina. 
Persons  so  affected  can  see  objects 
at  a  distance,  but  always  with 
some  effort  of  acconamodation.  If 
accommodation  be  paralysed  by 
means  of  atropine  everything  will  appear  blurred.  Since  accommoda- 
tion is  required  even  for  infinite  distance,  the  greatest  possible  effort 
will  be  insufiScient  to  bring  near  objects  into  accurate  focus,  and  the 
near  point  of  such  eyes  will  be  greater  than  normal.  Persons  with 
hypermetropia,  or  long-sightedness,  can  therefore  see  objects  at  a 
distance  perfectly  well,  but  are  unable  to  read  small  print,  since 
the  point  of  near  vision  is  too  far  from  the  eye  to  allow  the  small 
letters  to  subtend  a  sufficiently  large  angle. 

Both  these  disorders  can  be  corrected  by  suitable  spectacles. 
In  the  case  of  the  myopic  eye  we  need  lenses  which  will  convert  the 
parallel  rays  into  divergent  rays  ;  such  cases  are  treated  therefore  with 
concave  lenses.  Conversely;  hypermetropia  is  treated  with  convex 
lenses,  which  will  aid  the  too  feeble  refractive  power  of  the  eye,  and  so 
bring  parallel  rays  to  a  focus  on  the  retina  without  any  effort  of  accom- 


FlG.  262.  Diagrams  of  course  taken 
by  parallel  rays  in  entering  normal 
(emmetropic)  eye  (a),  hyper- 
metropic   eye    (b),     andj  myopic 

eye  (c). 


596  PHYSIOLOGY 

modation.  The  degree  of  myopia  or  hypermetropia  is  denoted  by 
the  refractive  power  of  the  lens  which  is  necessary  to  make  the  eye 
emmetropic. 

In  order  to  determine  the  refractive  power  of  any  eye  it  is  usual  to  employ 
Snellen's  test  type.  This  consists  of  a  series  of  letters  which  are  placed  at  a 
distance  of  five  metres  from  the  eye.  At  this  distance  the  visual  angle  subtended 
by  each  of  these  letters  is  so  small  that  a  clear  retinal  image  is  necessary  for 
their  recognition.  This  is  easy  in  the  case  of  a  normal  eye.  After  allowing 
the  patient  to  attempt  the  recognition  of  the  type  without  spectacles  he  is 
then  made  to  regard  it  through  a  weak  convex  lens.  If  the  patient  can  now 
read  as  well  as  or  better  than  before  he  is  hypermetropic,  since  it  is  only  the 
hypermetropic  eje  which  is  able  to  unite  convergent  rays  of  light  on  to  the  retina. 
If,  on  the  other  hand,  the  reading  of  the  type  is  made  more  difficult  the  patient 
is  either  normal  (emmetropic)  or  myopic.  In  the  latter  case  a  concave  lens  is 
tried.     If  the  reading  is  rendered  more  easy  by  this  means  the  patient  is  myopic. 

In  prescribing  the  lenses  for  hypermetropia,  the  strongest  lens  with  which 
the  patient  is  able  to  see  represents  the  degree  of  hypermetropia.  Since  now 
the  mechanism  for  accommodation  must  be  relaxed  as  far  as  is  possible,  the 
strength  of  such  a  lens  serves  as  a  measure  of  the  degree  of  hjT)ermetropia. 
On  the  other  hand,  in  myopia  the  degree  of  the  disorder  is  deterrmned  by  the 
weakest  lens,  by  means  of  which  the  patient  is  able  to  see  distant  objects. 

In  a  perfect  dioptric  mechanism  the  media  through  which  the 
light  passes  must  be  perfectly  transparent,  and  the  centres  of  curva- 
ture of  the  various  refracting  surfaces  must  lie  in  one  straight  line, 
i.e.  the  system  must  be  properly  centred.  In  neither  of  these  respects 
can  the  eye  be  regarded  as  perfect.  If  a  strong  beam  of  light  be 
thrown  into  the  eye,  the  refraction  of  the  beam  caused  by  the  slight 
difference  in  structure  between  adjacent  portions  of  the  cornea  and 
lens  makes  these  objects  immediately  visible,  and  the  field  of  vision 
is  filled  with  diffused  light  arising  from  the  illuminated  points  in  these 
structures.  Under  normal  circumstances,  however,  these  slight 
differences  in  the  regularity  of  the  refracting  media  do  not  make  any 
appreciable  difference  to  our  vision.  More  easily  detected  are  the  opacities 
due  to  structures  in  the  vitreous  humour.  These  opacities  can  be 
seen,  when  the  eyes  are  turned  towards  a  uniformly  illuminated  surface, 
as  small  dark  points  or  strings  of  beads,  which,  since  they  alter  their 
position  with  changes  in  the  direction  of  the  eyes,  are  often  spoken  of  as 
muscce  volitantes.  The  centring  of  the  eye  is  also  never  perfect.  In  the 
horizontal  meridian  the  optic  axes  of  the  cornea  only  diverge  about 
0*3°  from  the  axis  of  the  lens,  but  in  the  vertical  meridian  there  is 
as  much  as  1-3°  difference  between  the  two  axes.  Moreover  the  visual 
axis  does  not  correspond  exactly  with  the  optic  axis  of  the  eye.  The 
fovea  centraUs,  the  point  of  distinct  vision  on  which  the  image  of  any 
object  must  be  brought  in  order  to  see  it  as  distinctly  as  possible,  always 
lies  outside  and  somewhat  below  the  point  at  which  the  optic  axis 
strikes  the  retina.     The  angle  between  the  two  axes  is  often  spoken 


DIOPTRIC  MECHANISMS  OF  THE  EYEBALL 


597 


of  as  the  angle  a.  This  angle  in  the  horizontal  meridian  varies 
between  3-5°  and  7°,  and  in  the  vertical  meridian  is  about  3-5°. 

Although  this  divergence  of  the  axes  causes  a  certain  amount 
of  astigmatism  {v.  p.  598),  it  is  too  small  to  interfere  appreciably  with 
the  sharpness  of  vision. 

SPHERICAL  ABERRATION.  When  a  beam  of  parallel  rays 
falls  on  to  the  surface  of  a  spherical  lens  those  rays  which  pass  through 
the  circumference  are  converged  to  a  focus  which  lies  nearer  to  the 
lens  than  the  focus  of  those  rays  which  pass  through  its  centre.  In  an 
optical  instrument  the  blurring  of  the  image  thus  produced  is  counter- 
acted in  two  ways  : 

(1)  By  making  the  curvature  in  the  middle  of  the  lens  greater  than 
at  its  periphery. 

(2)  By  stopping  out  the  peripheral  rays  by  means  of  a  diaphragm, 
or  by  using  only  a  cylinder  cut  from  the  centre  of  the  lens.      It  is 


V    f 


familiar  to  every  photographer  that  where  sharpness  of  definition  is 
required  it  is  necessary  to  use  a  small  stop,  giving  a  corresponding 
increased  exposure. 

In  the  eye  spherical  aberration  is  diminished  by  both  these  means. 
The  curvature  of  the  lens  is  gxeater  towards  its  centre  than  at  its  cir- 
cumference, and  the  peripheral  rays  of  light  are  shut  out  by  a  circular 
diaphragm,  the  iris,  the  diameter  of  the  aperture  in  which  varies 
according  to  the  amount  of  light  faUing  into  the  eye,  and  according  to 
the  nearness  of  the  object  which  is  the  point  of  regard. 

CHROMATIC  ABERRATION.  The  refraction  of  light  in  passing 
from  a  lighter  to  a  denser  medium  is  due  to  the  fact  that  in  the  latter 
the  velocity  of  propagation  of  the  light  is  less  than  in  the  former. 
This  diminution  of  the  velocity  of  the  propagation  affects  rays  of 
various  wave-lengths  differently,  so  that  of  the  various  rays  which 
make  up  white  light  those  at  the  red  end  with  a  long  wave-length 
are  refracted  least,  and  those  at  the  violet  end  with  a  short  wave- 
length are  refracted  the  most.  On  this  account,  when  light  passes 
into  a  prism  it  is  spHt  up  into  its  component  rays  with  the  produc- 
tion of  a  spectrum.  The  same  splitting  up  of  rays  occurs  when 
light  passes  through  a  simple  lens.  As  is  shown  in  Fig.  203, 
the  violet  rays  come  to  a  focus  at  a  point  nearer  the  lens  than  the  red 


598  PHYSIOLOGY 

rays.  A  screen  held  at  v  will  therefore  show  a  bluish-violet 
centre  with  a  red  margin ;  at  r  the  centre  will  be  reddish  and  the 
margin  violet. 

In  optical  instrmnents  this  chromatic  aberration  is  corrected  by 
combining  glasses  of  different  powers  of  dispersion,  with  the  production 
of  so-called  achromatic  lenses.  In  the  eye  achromatism  is  practically 
uncorrected.  The  difierence  in  the  focus  of  red  and  violet  rays  in  the 
eye  amounts  to  about  0*5  nam. ;  hence,  if  we  are  looking  at  a  red  and  a 
violet  spot  situated  closely  together,  it  requires  a  greater  act  of 
accommodation  to  bring  the  image  of  the  red  spot  on  the  retina  than 
is  the  case  with  the  violet  spot.  The  red  spot  therefore  looks  nearer, 
i.e.  more  prominent.  It  may  be  this  special  effort  of  accommodation 
necessary  for  the  appreciation  of  red  that  makes  this  colour  stand  out, 
so  to  speak,  and  be  conspicuous  as  compared  with  the  other  colours  of 
the  spectrum. 

The  fact  that  as  a  rule  we  do  not  see  coloured  fringes  around 
every  object  that  we  look  at  is  due,  not  to  the  optical,  but  to  the 
physiological  qualities  of  the  eye.  When  white  light  falls  on  the  eye 
and  is  focused  by  the  latter  on  to  the  retina,  it  will  be  the  rays  ot 
medium  refrangibility  which  come  to  a  point  at  the  retina  ;  these 
optically  will  be  surrounded  with  a  halo  composed  of  the  red  and 
violet  rays,  as  is  shown  in  the  figure  at  /.  The  retina  is,  however, 
comparatively  insensitive  for  rays  at  the  two  extreme  ends  of  the 
spectrum.  Moreover  the  strong  illumination  produced  by  the  middle 
rays  of  the  spectrum,  i.e.  about  the  yellow,  at  the  centre  of  the 
illuminated  spot,  by  contrast  depresses  the  excitabiUty  of  the 
surrounding  parts  of  the  retina,  so  that  the  halo  due  to  the  red  and 
violet  rays  is  neglected  and  does  not  come  into  consciousness. 

ASTIGMATISM.  We  have  assimied  so  far  that  the  refracting 
surfaces  of  the  eye  are  practically  spherical ;  this  does  not  apply 
strictly  either  to  the  cornea  or  the  lens.  The  small  differences  between 
the  curvatures  of  the  cornea  in  the  horizontal  and  vertical  meridian 
towards  its  centre  do  not  as  a  rule  give  rise  to  appreciable  disorders  of 
vision.  In  many  cases,  however,  the  asymmetry  in  the  anterior  sur- 
face of  the  cornea  is  sufficient  to  cause  a  considerable  difference  in 
the  refraction  of  rays  in  the  different  meridians,  and  this  distiirbance  is 
known  as  astigmatism. 

The  curvature  of  the  vertical  meridian  of  the  cornea  is  nearly 
always  somewhat  greater  than  that  of  the  horizontal  meridian.  When 
this  difference  is  sufficiently  pronounced  it  becomes  impossible  for 
a  definite  image  of  a  point  of  light  to  be  formed  on  the  retina,  since 
the  rays  which  diverge  from  the  luminous  point  in  the  vertical  plane 
are  brought  to  a  focus  sooner  than  those  in  a  horizontal  plane.  Such 
an  eye  will  therefore  possess  two  posterior  foci,  one  for  the  vertical 


DIOPTRIC  MECHANISMS  OF  THE  EYEBALL 


599 


meridian;   the  other  for  the  horizontal  meridian.     The   manner  in 
which  such  rays  are  diverged  is  shown  in  Fig.  264. 

The  effects  of  astigmatism  are  especially  noticeable  when  the  patient 
is  trying  to  see  clearly  objects  composed  of  horizontal  and  vertical 
lines,  such  as  print.  A  vertical  hne  can  be  conceived  as  made  up  of  a 
series  of  points  each  of  which  sends  out  a  horizontal  sheaf  of  rays.  In 
the  same  way  a  horizontal  Une  is  distinguished  as  a  series  of  points 
sending  out  flat  sheafs  of  vertical  rays.  If  the  curvatm-e  of  the  cornea 
in  the  vertical  meridian  is  greater  than  in  the  horizontal  it  will  need 
a  greater  effort  of  accommodation  to  bring  the  vertical  lines  to  a  focus 
on  the  retina  than  it  does  to  bring  the  horizontal  lines.  In  reading 
therefore  there  is  a  constant  shifting  of  the  focus  of  the  eye,  and  the 


Fig.  264.    Diagram  showing  course  of  rays  n  an  astigmatic  eye.    (Waller.) 

The  curvature  of  the  cornea  is  greater  in  the  vertical  meridian 
vvv  than  in  the  horizontal  nkeridian  hhh.  Hence  the  rays  of  light 
coming  from  the  point  p  and  passing  through  the  vertical  meridian 
come  to  a  focus  at/^,  while  those  through  the  horizontal  meridian  come 
to  a  focus  at  f^.  There  is  thus  no  point  behind  the  cornea  at  which  all 
the  rays  from  p  will  come  to  a  focus,  and  the  image  of  the  point  must 
be  blurred,  being  elongated  in  a  horizontal  direction  at  P;  and  in  a 
vertical  direction  at  f^. 

mechanism  of  accommodation  becomes  rapidly  tired  and  strained, 
with  the  production  of  pain  in  the  eyes  or  of  headache.  ]n  order  to 
correct  astigmatism  it  is  necessary  to  find  out  first  the  curvature  of  the 
cornea  in  the  different  meridians,  and  then  to  reinforce  the  curvature 
of  the  weaker  meridian  by  means  of  a  cyhndrical  lens.  If  the  eye  is 
myopic  the  cylindrical  lens  may  be  concave  and  placed  so  that  its 
curvature  counteracts  that  of  the  cornea  in  the  meridian  in  which  the 
curvature  is  greatest. 

ACCOMMODATION 
The  rays  falhng  on  the  eye  from  a  point  of  light  at  a  distance 
greater  than  five  metres  from  the  eye  may  be  regarded  as  practically 
parallel,  and  are  converged  in  the  normal  eye  to  a  focus  on  the  retina. 
As  the  point  of  light  is  moved  nearer  to  the  eye  the  latter  is  still  able 
to  focus  the  rays  on  the  retina  through  a  considerable  range.  On 
approximating  the  points  of  light  to  a  distance  which  is  less  than  the 
near  point  of  distinct  vision,  the  rays  are  no  longer  converged  to  a 
point  on  the  retina,  and  a  blurred  image  is  the  result.     This  near  point 


600 


PHYSIOLOGY 


of  vision  may  be  determined  in  any  eye  by  finding  out  the  smallest 
distance  from  the  eye  at  which  small  print  can  be  easily  distinguished. 
The  distance  is  measured  by  means  of  a  graduated  rod  between  the 
eye  and  the  printed  object.  This  '  accommodation, '  by  which  the 
eye  is  able  to  focus  divergent  rays  on  to  the  retina,  imphes  either  a 


Fig.  265.     Diagram  of  phakoscope. 

change  in  the  distance  of  the  refracting  surfaces  from  the  retina,  or 
an  increase  in  the  total  refractive  powers  of  the  eye. 

In  man  and  the  higher  animals  it  is  by  the  latter  means  alone 
that  accommodation  is  efiected.  The  fact  that  accommodation,  as 
was  shown  by  Young,  may  be  carried  out  under  water,  i.e.  under 
conditions  in  which  the  curvature  of  the  cornea  does  not  cause  any 
appreciable  deviation  of  the  rays  passing  through  it,  shows  that  the 


a  b  c  a  b  c 

Fig.  266.     Diagram  of  reflected  images  from  cornea  and  lens  surfaces  seen 

in  phakoscope. 
a,  from  anterior  surface  of  cornea ;    b,  from  anterior    surface  of  lens  ; 
c,  from  posterior  surface  of  lens.     1,  during  accommodation  for  distance  ; 
2,  during  accommodation  for  near  objects. 

change  in  the  combination  cannot  be  located  in  the  cornea.  It  was 
shown  by  Helmholtz  that  the  essential  process  in  accommodation 
is  an  alteration  in  the  curvature  of  the  lens,  the  anterior  surface 
becoming  more  convex  when  the  eye  is  accommodated  for  near  objects. 

This  may  be  shown  by  means  of  the  phakoscope  (Fig.  265).  This 
is  simply  a  box,  blackened  inside,  with  holes  at  a,  b,  c,  and  d.  At 
a  is  the  observer's  eye  ;  at  b  the  observed  eye.  Across  the  middle 
oi  d  a.  wire  is  stretched. 

A  candle  is  placed  at  c.     The    observer    at    a    then    sees   three 


DIOPTRIC  MECHANISMS  OF  THE  EYEBALL 


601 


reflections  of  the  candle  from  the  eye  at  6  :  a  bright  erect  image 
from  the  anterior  surface  of  the  cornea  ;  a  larger  but  dimmer  erect 
image  from  the  anterior  surface  of  the  lens  ;  and  a  small  very  dim 
inverted  image  from  the  posterior  surface  of  the  lens.  These  images 
must  be  observed  first  when  the  eye  at  b  is  accommodated  for  a 
distant  object,  and  then  when  it  is  accommodated  for  the  wire  stretched 
across  the  opening  d.  It  will  be  noticed  that  the  change  of  accom- 
modation from  far  to  near  objects  is  accompanied  by  a  change  in  the 
second  image  (that  from  the  anterior  surface  of  the  lens),  which  becomes 


Fig.  267.    Diagram  to  illustrate  principle  of  ophthalmometer.    (After  Schesck.) 


smaller.  The  change  in  this  image  is  more  easily  seen  if  the  candle 
be  made  to  throw  two  images  on  the  eye  by  interposing  a  double 
prism  at  c.  Then,  as  the  lens  becomes  more  convex  to  accommodate 
for  near  objects,  the  two  images  of  the  candle  reflected  from  its  anterior 
surface  approach  one  another  (Fig.  266). 

By  measuring  the  size  of  the  image  of  the  candle  produced  by  the 
anterior  surface  of  the  lens,  and  knowing  the  size  of  the  candle  itself  and 
the  distance  from  the  observed  eye,  it  is  possible  to  calculate  the 
curvature  of  the  lens  in  the  living  body. 

The  radius  of  curvatxire  of  a  reflecting  surface  is  given  approximately  by 
the  following  formula  : 


R=2 


a.b 


where  R  is  the  radius  of  curvature,  a  the  distance  of  the  object,  b  the  t*ize 
of  the  image,  C  the  size  of  the  object.  The  object  generally  used  is  the  distance 
between  two  Ughts  or  two  white  objects  called  mires  ;  the  '  image  '  being  the 
distance  between  their  images.     Owing  to  the  movements  of  the  eye  the  latter 


602 


PHYSIOLOGY 


cannot  be  accurately  measured  by  the  usual  method,  employed  by  physicists* 
of  looking  at  the  images  through  a  telescope  which  has  a  micrometer  at  the 
focus  of  the  object.  This  difficulty  is  overcome  by  doubling  the  image.  For 
this  pm-pose  Helmholtz  devised  the  ophthalmometer,  in  which  the  doublmg 
is  brought  about  by  two  plane  glass  plates  set  at  a  variable  angle  to  one  another. 
The  principle  of  the  instrument  can  be  gathered  from  the  diagram  (Fig.  267).  We 
may  suppose  it  is  necessary  to  measure  the  line  ab,  which  m&y  be  taken  to  repre- 
sent an  image  reflected  from  the  anterior  surface  of  the  cornea  or  lens.  If  we  look 
at  this  line  through  a  plate  of  glass  the  plane  of  which  is  at  right  angles  to  our 
line  of  sight,  no  distortion  of  the  line  ab  takes  place.  If  however  the  plate 
be  placed  obUquely,  as  at  gr^  gr^,  there  will  be  an  apparent  shifting  of  the  line 
sideways  to  cd.  In  the  ophthalmometer  there  are  two  glass  discs,  Qi  gi,  and 
g^  g^f  one  immediately  over  the  other,  so  placed  that  the  image  ah  is  looked 
at  through  the  junction  between  the  two  plates.     The  plates  are  then  turned, 


as  in  the  diagram,  until  ah  appears  as  two  distinct  lines  ec  and  cd  just  touching 
one  another  at  c.  At  this  point  each  image  of  the  line  ah  has  been  shifted 
through  one  half  the  length  of  ab.  Knowing  the  thickness  of  the  plates  and 
their  refractive  index,  it  is  easy  to  calculate,  from  the  angle  through  which 
the  plates  have  been  turned,  the  apparent  shifting  of  the  line  ah.      This  lateral 

movement  amounts  to  ac,  i.e.  to  —  ,  and  we  have  merely  to  double  this  residt 

in  order  to  obtain  the  actual  size  of  the  image  on  the  cornea  or  lens. 

A  table  is  generally  supplied  Mith  the  instrument  giving  the  actual  size 
of  the  image  corresponding  to  the  angle  through  which  the  plates  have  been 
turned  ;  the  eye  always  being  placed  at  a  constant  distance  from  the  instru- 
ment and  the  luminous  object  always  being  the  same  size. 
The  size  of  the  image  is  calculated  in  the  following  way*  : 
"  Let  aa  (Fig.  268)  be  one  of  the  plates,  AB  the  incident,  CD  the  refracted 
ray.  Then,  since  the  refracted  ray  is  parallel  to  the  incident  ray,  the  angle 
ABN  is  equal  to  the  angle  DCN'  (=  a).  Similarly  the  angle  of  refraction  CBn 
is  equal  to  the  angle  BCn'  (=/3).  Let  h  be  the  tliickness  of  the  glass  plate. 
Produce  DC  backwards  to  A'.  It  is  required  to  find  the  perpendicular  distance 
between  A  and  A'  (=»  x). 

*  Parson's  "  Elementary  Ophthalmic  Optics." 


DIOPTRIC  MECHANISMS  OF  THE  EYEBALL  603 

Now  -^  =  sin  BCA' 

=  sin  (n'CA'  -  n'CB) 
—  sin  (a  —  /)). 

And  —  =  cos  /). 

Therefore  x  =  h.  '^  ^"  '  ^'\ 

cos  iJ 

If  there  are  two  such  plates,  arranged  as  in  Fig.  267,  then 
a'b"  =  2x 

cos  /3 

The  angle  a  is  measured  by  the  instrument ;  the  angle  /j  is  calculated  from 
the  formula  for  refraction,  sin^a  =  n.  sin  /3  ;  and  the  thickness  of  the  plates,  h, 
is  kno^vn.     Therefore  the  distance  between  the  images  can  be  calculated." 

In  the  normal  eye  in  a  position  of  repose,  z.e.  focused  for  parallel 
rays,  the  curvatures  of  the  three  principal  refracting  surfaces  are  as 
follows  : 

mm. 
Anterior  surface  of  cornea       ....         8 
Anterior  surface  of  lens  ....       10 

Posterior  surface  of  lens  ....         6 

During  maxiniuin  accommodation  the  radius  of  curvature  of  the 
anterior  surface  of  the  lens  changes  to  6  mm.  At  the  same  time  there 
is  a  slightly  increased  curvature  at  the  periphery  of  the  posterior 
surface,  but  the  effects  of  this  change  are  neghgible  as  compared  with 
those  produced  by  the  alteration  of  the  anterior  surface. 

In  order  to  determine  the  method  in  which  this  change  in  curvature 
of  the  anterior  surface  of  the  lens  is  brought  about  we  must  refer  in 
some  detail  to  the  structure  of  the  anterior  half  of  the  eye  and  the 
manner  in  which  the  lens  is  hung  up  between  the  aqueous  and  vitreous 
humours.  The  outermost  layer  of  the  eye  is  formed  by  the  sclerotic 
coat,  a  strono;  tough  membrane  of  white  fibrous  tissue.  In  front  this 
is  continuous  with  the  cornea,  whicl" ,  having  a  smaller  radius  of  curva- 
ture than  the  globe  of  the  eye,  protrudes  like  a  watch-glass  from  its 
anterior  surface.  The  main  substance  of  the  cornea  is  formed,  hke 
the  sclerotic,  by  white  fibrous  tissue,  modified  however  in  its  consis- 
tence so  as  to  be  perfectly  transparent  instead  of  white  and  opaque 
like  the  rest  of  the  sclerotic.  Internal  to  the  sclerotic  is  the  choroid 
coat,  a  membrane  with  a  double  pigmented  internal  layer,  and  supplied 
with  blood-vessels  which  furnish  the  vascular  supply  to  the  whole  eye. 
In  front  the  choroid  coat  presents  a  series  of  folds,  arranged  in  a 
circle  around  the  anterior  part  of  the  cavity  of  the  vitreous  and  known 
as  the  ciliary  processes.     In  front  of  the  cihary  processes  the  choroid 


604  PHYSIOLOGY 

leaves  the  sclerotic  and  hangs  as  a  curtain  into  the  cavity  of  the 
aqueous  humour,  between  the  cornea  and  the  lens.  The  curtain, 
which  is  known  as  the  iris,  presents  a  circular  orifice  at  its  centre,  the 
pupil,  and  is  provided  with  muscular  fibres  by  means  of  which  the  pupil 
may  be  constricted  or  dilated.  The  posterior  surface  of  the  iris,  hke 
the  inner  surface  of  the  choroid  generally,  is  lined  by  a  pigmented 
epithehum.  The  posterior  layer  of  the  cornea  is  formed  by  a  tough 
elastic  membrane  [Desceniefs  membrane)  which  is  covered  posteriorly 
by  a  layer  of  cubical  epithehal  cells.  At  the  circumference  of  the 
cornea  Descemet's  membrane,  or  the  posterior  elastic  lamina,  breaks 
up  into  a  number  of  fibres,  which  pass  outwards  and  backwards  to  be 
inserted  into  the  anterior  part  of  the  choroid  and  root  of  the  iris.  These 
fibres  are  the  ligamentum  pectinatum  iridis.  Between  the  fibres  of  the 
ligamentum  pectinatum  are  a  number  of  spaces  lined  wdth  endo- 
thehum  continuous  with  the  anterior  chamber  and  known  as  the 
spaces  of  Fontana,  and  outside  these  spaces,  in  the  corneo-sclerotic 
junction,  is  a  circular  sinus  continuous  with  the  venous  system,  the 
canal  oj  Schlemm  or  sinus  venosus.  The  iris  rests  at  its  inner  margin 
on  the  lens,  so  dividing  the  cavity  of  the  aqueous  humour  into  two 
parts.  In  front  is  the  anterior  chamber,  and  behind  the  posterior 
chamber,  which  is  a  small  annular  space,  triangular  in  cross-section, 
and  bomided  by  the  iris  in  front,  the  lens  behind,  and  the  cihary 
processes  externally. 

The  crystalline  lens,  made  up  of  radiating  lens  fibres,  each  of 
which  is  produced  by  the  modification  of  an  epithelial  cell,  is  biconvex, 
the  posterior  surface  being  more  convex  than  the  anterior.  It  is 
surroimded  by  a  tough  structureless  membrane,  the  capsule  of  the 
lens,  and  rests  in  a  cavity  hollowed  out  of  the  anterior  surface  of  the 
vitreous  humour.  At  its  circumference  it  is  hung  up  and  fastened 
to  the  ciliary  processes  by  the  suspensory  hgament,  or  zonule  of 
Zinn  [zonula  ciliaris).  (Fig.  269.)  This  ligament  is  formed  in  the 
following  way : 

The  vitreous  humour  is  bounded  externally  by  the  hyaloid  mem- 
brane, which  separates  it  from  the  retina.  In  front  the  hyaloid 
membrane  passes  behind  the  lens,  but  as  it  lies  on  the  ciliary  processes 
is  closely  adherent  to  these  structures  and  sends  oii  fibres  which  pass 
radially  from  the  ciliary  processes  to  the  capsule  of  the  lens  and  form 
the  zonule,  or  suspensory  ligament.  The  greater  part  of  the  sus- 
pensory ligament,  i.e.  from  the  ora  serrata  of  the  retina  to  the  edge 
of  the  cihary  processes,  is  closely  attached  to  these  processes.  From 
their  edge  a  number  of  fibres  pass  and  fuse  at  their  inner  extremities  with 
with  the  lens  capsule.     These  fibres  are  arranged  in  three  groups  : 

(1)  The  anterior  group  passing  to  the  anterior  capsule  of  the  lens. 

(2)  A  middle  group  passing  to  the  equator  of  the  lens. 


DIOPTRIC  MECHANISMS  OF  THE  EYEBALL 


605 


(:3)  A  posterior  group  lying  close  to  the  hyaloid  membrane  and 
passing  to  the  posterior  lens  capsule. 

The  suspensory  ligament  is  always  in  a  condition  of  tension. 
If  the  finger  be  pressed  on  the  outside  of  the  eyeball,  it  will  be  felt 
that  this  organ  presents  a  resistance  to  deformation  which  cannot  be 
ascribed  simply  to  the  firmness  of  the  sclerotic  coat,  but  must  be 
determined  by  the  existence  of  a  positive  pressure  in  the  fluid  filling 
the  eyeball.     This  pressure,  which  is  known  as  the  intra-ocular  jyressure, 


Sinus 


Conjunctiva 


Retina 


Fig.  269.     Section  through  anterior  part  of  eyeball  to  show  mode  of 
suspension  of  lens.    (After  5Ierkel  and  Kallius.) 


may  be  measured  by  means  which  we  shall  have  to  discuss  later' 
and  is  found  to  amount  to  about  25  mm.  Hg.  As  a  result  of  this 
pressure  the  membranes  which  confine  the  fluids  of  the  eyeball  are 
distended,  i.e.  pressed  outwards,  and  this  pressure  keeps  the  bases 
of  the  ciliary  processes  pressed  against  the  choroid  coat  and  thus 
enables  them  to  withstand  the  pull  exerted  by  the  tense  suspensory 
ligament. 

The  pull  exerted  by  the  suspensory  ligament  affects  mainly  the 
tough  anterior  surface  of  the  lens  capsule  and  so  has  a  constant 
flattening  effect  on  the  anterior  surface  of  the  lens.  Tliis  may  be  proved 
by  measuring  the  curvature  of  the  lens  in  a  recently  excised  eye,  and 
then  removing  the  lens  altogether  from  the  eyeball  and  measuring 


606  PHYSIOLOGY 

the  curvatures  of  its  surfaces  again.  It  will  be  found  that,  as  soon 
as  the  lens  is  free  from  its  attachments  in  the  eyeball,  the  curvature  of 
its  anterior  surface  is  increased.  The  change  therefore  in  the  lens, 
which  is  responsible  for  the  alterations  in  its  refractive  power  deter- 
mining accommodation,  may  be  effected  by  any  means  which  will 
relax  the  suspensory  ligament,  such,  for  instance,  as  approximation 
of  the  ciliary  processes  to  the  margin  of  the  lens.     This  movement  of 


Fig.  270.     Diagram  of  mechanism  of  accommodation.     (Tigebstedt 
after  Schon.) 

The  dotted  line  shows  the  form  of  the  lens  during  accommodation  for 

near  objects. 

the  cihary  processes  is  effected  by  the  ciliary  muscle.  The  attach- 
ments of  this  muscle  are  shown  in  Fig.  269.  It  forms  a  circle  of 
unstriated  muscle  fibres,  triangular  in  cross-section,  and  extending 
round  the  whole  circumference  of  the  eyeball.  The  fibres  of  the  muscle 
are  divided  into  three  groups  : 

(a)  The  meridional  fibres,  which  run  from  the  corneo-sclerotic 
junction  backwards  and  outwards  to  be  attached  to  the  anterior  part 
of  the  choroid  coat  behind  the  ciliary  processes. 

(6)  The  radial  fibres,  which  pass  from  the  margins  of  the  canal  of 
Schlemm,  and  from  the  fibres  of  the  ligamentum  pectinatum  to  be 
attached  behind  to  the  whole  extent  of  the  cihary  processes. 


DIOPTRIC  MECHANISMS  OF  THE  EYEBALL 


607 


(c)  The  circular  bundle,  which  forms  a  ring-muscle,  composed  of 
fibres  running  around  the  circumference  of  the  eye  in  the  inner  part 
of  the  ciUary  processes.  Tliis  bundle  is  best  marked  in  hypermetropic 
eyes  and  is  almost  absent  in  myopic  eyes. 

When  this  muscle  contracts  it  draws  the  anterior  part  of  the  choroid 
and  the  cihary  processes  forwards  and  inwards,  while  the  ring-fibres 
approximate  the  ciliary  processes  to  the  margin  of  the  lens.  By  this 
approximation  of  the  ciliary  processes  to  the  lens  the  suspensory 
ligament  is  relaxed,  and  the  anterior  surface  of  the  lens  bulges,  i.e. 
becomes  more  convex  as  a  result  of  its  inherent  elasticity  (Fig.  270). 

This  explanation  of  accommodation,  which  was  first  put  forward 
by  Helmholtz,   is   almost  universally  accepted.     According  to  some 


Fig.  271.    Accommodation  in  the  cat's  eye.  b,  distance;   a,  for  near  vigion. 

(After  Beeb.) 

Two  needles  have  been  passed  through  edge  of  cornea  into  ciliary  bodies, 
to  show  forward  movement  of  latter  during  accommodation. 


the  change  of  shape  of  the  lens  during  accommodation  is  brought 
about  by  the  actual  pressure  of  the  ciliary  processes  on  its  margin 
by  which  the  middle  of  its  anterior  surface  is  pressed  forwards. 
According  to  Tscherning  this  effect  is  produced,  not  by  relaxation, 
but  by  a  tightening  of  the  suspensory  ligament  through  the  con- 
traction of  the  ciliary  muscle.  There  is  no  doubt,  however,  that 
during  forced  accommodation,  such  as  can  be  brought  about  by 
instillation  of  eserine  into  the  eye,  which  produces  spasm  of  the 
ciliary  muscle,  the  suspensory  ligament  is  so  relaxed  that  the  lens  lies 
loosely  in  the  eyeball.  Bending  the  head  dox\Tiwards  causes  there- 
fore an  actual  change  in  the  position  of  the  lens,  which  may  drop  as 
much  as  1  mm.  forwards  towards  the  cornea.  Under  the  same  condi- 
tions a  quick  movement  of  the  head  causes  the  lens  to  shake,  and  the 
quiver  of  the  lens  can  be  seen  by  an  external  observer  and  proved 
by  the  subjective  oscillation  of  external  objects  which  is  noticed 
after  such  a  movement.  Moreover,  if  a  needle  be  passed  through  the 
sclerotic  so  that  its  point  lies  in  the  ciliary  processes,  stimulation  of 
the  cihary  muscle  causes  a  movement  of  the  outer  part  of  the  needle 


608 


PHYSIOLOGY 


backwards,  showing  that  the  point  of  the  needle  which  is  in  the  ciliary 
processes  has  been  moved  forwards  (Fig.  271).  The  loosening  of  the 
lens  during  spasm  of  accommodation  is  well  shown  in  rare  cases 
where  there  is  congenital  absence  of  the  whole  iris.  In  such  cases  the 
shaking  of  the  patient's  head  is  seen  to  cause  an  -oscillation  of  the 
lens  within  the  eyeball. 

During  accommodation  the  increased  curvature  of  the  anterior  sur- 
face of  the  lens  causes  an  approximation  of  this  surface  to  the  cornea, 
which  may  be  directly  observed  {cp.  Fig.  271),  especially  in  people  with 
somewhat  prominent  eyes.  No  change  takes  place  in  the  intra- 
ocular pressure,  in  either  aqueous  or  vitreous  cavities,  as  the  result 
of   accommodation.       The   passage   of   fluid   takes   place   with  such 

f.  h  c         ®^^®  between  the   fibres   of    the    suspensory 

§  ligament  that  a  slight  movement  of  the  lens 

fa       forwards  or  backwards  does  not    upset    the 
equality  of  pressures  in  the  two  chambers. 

THE  RANGE  OF  ACCOMMODATION. 
Assuming  that,  as  is  the  case  with  the  normal 
eye,  the  tension  of  the  suspensory  ligament  is 
suflScient  to  keep  the  eye  focused  for  parallel 
rays,  the  near  point  of  vision  will  be  determined  by  the  unconstrained 
shape  of  the  lens,  i.e.  the  amount  by  which  its  curvature  can  increase 
when  the  suspensory  ligament  is  completely  relaxed. 

The  shape  of  the  lens  varies  with  age,  its  convexity  being  greatest 
directly  after  birth  and  diminishing  steadily  from  that  time  to  the 
age  of  sixty  or  seventy  (Fig.  272).  In  consequence  of  the  small  size 
of  the  eyeball,  the  eye  at  birth  is  generally  somewhat  hypermetropic, 
but  from  the  age  of  ten  onwards  we  find  that  the  point  of  near  vision 
recedes  continuously  with  advancing  age.  The  range  of  accom- 
modation is  measured  by  the  strength  of  the  lens  which  will  give  to 
rays  coming  from  the  near  point  of  distinct  vision  the  same  direction 
as  if  they  came  from  the  far  point.  In  a  normal  eye  the  far  point 
is  at  infinite  distance  and  the  rays  are  parallel.  The  change  in  the 
range  of  accommodation  with  advancing  years  is  shown  in  the 
following  Table  : 

Range  of  accommodation 
in  dioptres 

14 


Fig.  272.   Lens  from  human 

eye  at  different  periods  of 

life.   (Allen  Thomson.) 

a,  at  birth  ;    b,  adult ; 

c,  old  age. 


Age 


10 
20 
30 
40 
50 
60 
70 


10 
7 

4-5 
2-5 
1 
0-25 


This  gradual  diminution  in  the  range  of  accommodation  gives 


DIOPTRIC  MECHANISMS  OF  THE  EYEBALL  609 

rise  finally  to  disturbances  of  vision  which  are  known  as  presbyopia. 
The  ordinary  reading  distance  is  about  ten  inches.  A  smaller  distance 
than  this  is  rarely  made  use  of  even  in  youth,  when  the  point  of  near 
vision  is  only  three  or  four  inches  from  the  eye,  on  account  of  the 
effort  required  to  converge  the  axes  of  the  two  eyes  to  this  extent. 
The  effect  of  the  gradual  diminution  in  the  elasticity  of  the  lens  is 
noticed  as  soon  as  the  point  of  near  vision  recedes  beyond  ten  or 
twelve  inches,  i.e.  25  to  30  cm.  This  occurs  as  a  rule  between  forty- 
five  and  fifty,  when  we  begin  to  experience  difficulty  in  reading  small 
print,  since  the  visual  angle  subtended  by  such  print  at  a  distance 
over  ten  or  twelve  inches  is  too  small  to  allow  of  distinct  vision. 
The   condition   of    presbyopia,   is   remedied   by    employing  reading 


Fig.  273.     Accommodation  in  a  bird's  eye.     (Beeb.) 
R,  rest ;   A,  accommodation  for  near  objects. 

glasses,  i.e.  by  wearing  spectacles  which  converge  the  rays  of  light 
and  so  enable  small  objects  to  be  brought  nearer  to  the  eye  than  its 
near  point.  It  is  evident  that  these  glasses  must  be  strengthened 
continually  with  advancing  age.  No  trouble  is  experienced  in  seeing 
distant  objects,  the  refraction  of  the  eye  at  rest  remains  as  before. 
The  dimness  of  vision  in  extreme  old  age  for  distant  as  well  as  near 
objects  is  due  to  changes,  not  in  the  refractive  power  of  the  eye,  but 
in  the  transparency  of  the  refractive  media,  such  as  cataract,  i.e. 
opacity  of  the  lens,  opacity  of  the  cornea,  and  so  on.  The  former  con- 
dition can  often  be  remedied  by  extracting  the  lens  and  replacing  it 
by  glasses  of  ten  dioptres. 

THE  COMPARATIVE  PHYSIOLOGY  OF  ACCOMMODATION 
The  mechani.sm  of  acconiniodation  wliich  we  have  studied  in  man  is  found 
with  very  Uttle  modification  tliroughout  the  whole  group  of  nianinialia,  though, 
in  the  domestic  animals  at  any  rate,  the  range  of  accommodation  is  very 
much  less  than  in  man.  On  examining  other  t^-pes  of  animals  we  meet, 
as  was  showii  by  Beer,  an  anuizing  variety  of  nu^thods  by  whieh  the  foeusing 
range  of  the  eye  may  be  altered.     In  order  to  bring  distinct  images  of  objects 

39 


610 


PHYSIOLOGY 


at  various  distances  on  to  the  retina,  practically  every  possible  focusing  method 
is  made  use  of  in  one  type  or  another  of  the  animal  kingdom.  The  following 
details  are  taken  from  Beer's  papers. 

In  birds  the  eye,  like  that  of  man,  is  normally  focused  for  distant  objects, 
and  accommodation  for  near  objects  is  accomplished  by  a  change  in  curvature 
of  the  anterior  surface  of  the  lens.  Whereas,  however,  in  man  the  suspensory 
ligament  is  relaxed  by  a  drawing  forwards  of  the  choroid  membrane,  in  the 
bird's  eye  this  relaxation  is  effected  by  a  drawdng  backwards  of  the  posterior 

A 


Fig.  274.  Diagrams  from  Beer  to  show  mode  of  accommodation  {for 
distance)  in  a  fish, 
A,  vertical  section  of  the  eyeball ;  B,  view  of  eye  from  front ;  L,  lens  ; 
Ls,  suspensory  ligament ;  J,  iris ;  Rl,  retractor  lentis  or  '  campanula ' ; 
C,  changes  in  position  of  lens  when  eye  is  accommodated  for  an  object  at 
varying  distances. 

lamina  of  the  cornea,  where  it  breaks  up  into  the  ligamentum  pectinatum  iridis. 
In  these  eyes  the  main  attachment  of  the  suspensory  ligament  is  to  the  liga- 
mentum pectinatum  ;  the  retraction  of  this  ligament  is  effected  by  a  special 
muscle  known  as  Crampton's  muscle,  which  corresponds  to  the  ciliary  muscle 
in  man,  but  unlike  this  consists  of  striated  voluntary  muscle.  This  movement 
of  the  posterior  elastic  lamina  of  the  cornea  can  be  easily  showTi  by  passing 
two  needles  through  the  comeo-sclerotic  junction  until  their  points  lie  in  the 
anterior  chamber.  On  exciting  CVampton's  muscle  electrically,  the  outer 
end  of  the  needle  moves  forwards,  showing  that  the  deeper  part  of  the  comeo- 
sclerotic  junction  is  being  pulled  backwards  towards  the  ciliary  portion  of  the  eye 
(Fig,  273).    The  histologieal  character  of  the  muscle  of  accommodation  in  birda 


DIOPTRIC  MECHANISMS  OF  THE  EYEBALL  Oil 

seems  to  be  connected  with  the  rapid  accommodation  that  is  necessary  wiien  a 
bird  swoops  down  towards  the  ground  to  pick  up  some  food  insect.  Moreover, 
since  binocular  ^asion  is  not  present  in  many  birds,  and  convergence  of  the 
optic  axes  must  be  minimal,  it  is  probable  that  the  contractions  of  CVampton's 
muscle  play  a  great  part  in  guiding  the  movements  of  the  bird,  and  especially 
in  aiding  it  to  judge  distances.  In  ourselves  such  judgment  is  very  faulty 
without  the  co-operation  of  the  two  eyes. 

In  amphibia  and  snakes,  which  at  rest  are  also  focused  for  distance,  active 
accommodation  for  near  objects  is  effected,  not  by  change  in  curvature  of  the 
lens,  but  by  an  increase  in  the  distance  between  the  lens  and  the  retina.  In 
amphibia  the  ciliary  muscle,  which  lies  between  the  root  of  the  iris,  the  sclerotic 
and  choroid,  causes  a  rise  of  pressure  in  the  vitreous  cavity,  and  the  lens,  being 
the  most  movable  part  of  the  boundary  wall  of  this  ca\dty,  is  pushed  forwards 
towards  the  cornea.  The  aqueous  humour,  which  is  displaced  by  this  forward 
movement  of  the  lens,  finds  a  place  in  the  lateral  angle  of  the  eye,  which  is 
increased  in  depth  by  the  pull  of  the  muscle  fibres. 

In  snakes  the  same  action  is  effected  by  a  muscle,  often  cross-striated,  which 


J^  A 

Fig.   275.     Accommodation  in  eye  of  sepia.     (Beer.) 
R,  at  rest ;   A,  during  accommodation  (for  distance). 

is  situated  in  the  root  of  the  iris.  In  both  these  cases  the  movement  of  accom- 
modation is  unaffected  by  opening  the  aqueous  ca\nty,  whereas  in  mammals 
it  is  at  once  rendered  impossible  if  the  aqueous  cavity  be  laid  open. 

Most  of  the  teleostean  fishes  are  short-sighted,  i.e.  at  rest  they  are  focused 
for  near  objects.  Active  accommodation  of  these  animals  diminishes  the 
refractive  power  of  the  eye,  so  that  accommodation  occurs  for  distant  objects. 
In  the  fish's  eye  there  are  no  ciliary  processes,  ciliary  muscle,  zonule  of  Zinn, 
or  spaces  of  Fontana,  such  as  are  foimd  in  the  higher  vertebrata.  The  iris 
only  approaches  the  margin  of  the  lens,  and  does  not  shut  out  its  peripheral 
rays.  Tlie  lens,  which  is  spherical  (Fig.  274),  is  hung  up  by  means  of  a  flat 
band  attached  to  its  upper  pole.  This  is  kno^vn  as  the  '  suspensory  ligament,' 
but  is  quite  different  in  structure  and  mechanism  from  the  suspensorj'  ligament 
or  zonule  of  Zinn  of  the  vertebrate  eye.  From  the  lower  and  inner  pole  of 
the  lens  a  dark  pigmented  structure  passes  backwards  ;  this  was  described 
by  its  first  discoverer  as  the  campanula,  but  since  it  is  muscular  in  character 
is  better  named  the  'retractor  lentis.'  On  stimulation  this  muscle  pulls  the 
lens  backwards,  and  so  lessens  the  distance  between  it  and  the  retina,  in  this 
way  accommodating  the  eye  for  distance. 

The  eye  of  the  cephalopod  mollusc,  such  as  sepia,  is  also  short-sighted,  and 
active  accommodation,  as  in  the  fish's  eye,  is  accommodation  for  distance. 
The  mechanism  is,  however,  quite  different.  The  globe  of  the  oephalojiod's 
eye  has  the  shape  showii  in  the  diagram  (Fig.  275).  The  most  resistant  part 
of  the  globe  is  formed  by  a  strong  ring  of  curtilage  wiiieii  passes  roinul  the 
equator  of  the  eye.  The  rest  of  the  sclerotic  is  formed  of  delicate  membrane, 
which  is  thinnest  in  the  ring  just  behind  the  cartilaginous  ring.    IntheiMUerioj: 


612  PHYSIOLOGY 

wall  of  the  eye  is  a  strong  muscular  ring,  composed  of  meridional  fibres,  which 
run  from  the  cartilaginous  ring  to  be  inserted  into  the  ciliary  processes  or  corpus 
ciliare,  which  is  closely  attached  to  the  equator  of  the  lens. 

When  this  muscle  contracts  it  pulls  back  the  whole  anterior  wall  of  the 
eye  together  with  the  lens,  approximatmg  it  to  the  retina.  This  movement 
is  of  necessity  accompanied  by  a  rise  of  ocular  pressure,  but  room  for  the  dis- 
placed fluid  is  found  bj^  a  bulging  of  the  walls  of  the  eyeball  at  their  thinnest 
part,  i.e.  just  behind  the  cartilaginous  ring,  so  that  there  is  an  actual  diminu- 
tion of  the  distance  between  the  lens  and  the  retina. 

In  every  class  of  animals,  except  in  the  cephalopod  and  in  birds,  species  are 
fomid  which  possess  no  power  of  accommodation  at  all,  or  only  to  a  very  slight 
extent.  This  is  the  case  in  frogs,  alligators,  vipers,  and  in  many  rodents.  Many 
of  these  animals  are  distinguished  by  nocturnal  habits,  and  in  dayhght  their 
pupils  may  be  constricted  to  such  an  extent  as  to  render  accommodation 
mmecessary.  In  many  of  them,  too,  the  exact  form  of  an  object  is  not  so 
important  as  the  power  to  follow  its  movements.  In  such  cases  the  movement 
of  the  extrinsic  ocular  muscles  or  of  the  head  are  more  important  than  the 
exact  focusing  of  the  object  on  the  retina. 


THE  FUNCTIONS  OF  THE  IRIS 

The  iris  is  the  forward  prolongation  of  the  pigmented  choroid 
coat.  It  is  covered  anteriorly  by  a  layer  of  epithelium  continuous 
with  Decemet's  epithelium,  and  behind  by  a  thick  layer  of  pigmented 
epithelium  which  is  prolonged  forwards  from  the  retina.  It  is 
composed  of  delicate  connective  tissue,  attached  at  its  circumference 
to  the  fibres  of  the  hgamentum  pectinatum,  and  contains  two  sets  of 
unstriated  muscular  fibres.  The  one  set,  the  sphincter  pupillcB,  is 
composed  of  fibres  which  run  a  circular  course  around  the  margin  of 
the  pupil.  The  other  set,  the  dilatator  fwpillce,  forms  a  flattened 
layer  of  radiating  fibres,  which  lie  close  to  the  posterior  surface  and 
extend  from  the  attachment  of  the  iris  nearly  to  the  rim  of  the  pupil. 

The  pigment  in  the  iris  and  choroid  serves  the  same  purpose  as  the 
blackened  lining,  which  is  supplied  to  every  optical  instrument,  in 
preventing  dispersion  of  the  incident  light,  and  therefore  preventing 
any  light  falling  on  the  retina  except  those  rays  which  pass  through 
the  pupil  and  refractive  surfaces  of  the  eye.  The  pigment  in  the  iris 
has  an  additional  importance  in  that  it  enables  this  organ  to  act  as  a 
diaphragm.  It  not  only  shields  the  retina,  the  sensory  apparatus  of 
the  eye,  from  the  effects  of  any  excess  of  illumination,  but,  by  stopping 
out  the  rays  of  light  passing  through  the  periphery  of  the  lens,  it 
diminishes  spherical  aberration  and  enables  a  clear  image  of  external 
objects  to  be  formed  on  the  back  of  the  eyeball.  The  diameter  of 
the  pupil  is  continually  varying,  according  to  the  amount  of  light 
falling  into  the  eye  and  the  condition  of  the  mechanism  of  accom- 
modation. 

Contraction  of  the  pufil  occurs  under  the  following  circumstances  : 

(I)  When  light  falls  on  the  retina.     This  movement,   which   is 


DIOPTRIC  MECHANISMS  OF  THE  EYEBALL  (WZ 

known  as  '  the  light  reflex,'  is  determined  by  a  contraction  of  the 
sphincter  pupillse,  together  with  a  relaxation  of  the  dilatator  muscle. 
The  contraction  ensues  within  a  period  of  0-4  to  0-5  sec.  after  the 
moment  at  which  the  light  has  access  to  the  retina,  and  attains  its 
maximum  within  0-1  sec.  In  man  as  well  as  in  other  animals  which 
have  binocular  vision,  and  in  which  therefore  there  is  a  partial  decussa- 
tion of  the  fibres  of  the  optic  nerves  in  the  optic  chiasma,  the  reflex 
is  bilateral,  i.e.  light  falling  into  one  eye  causes  simultaneous 
contraction  of  both  pupils.  In  the  higher  animals  this  reaction 
of  the  pupil  to  light  demands  the  integrity  of  the  nervous  paths 
between  the  eye  and  the  brain  ;  but  in  many  of  the  lower  animals, 
e.g.  in  the  frog  and  eel,  the  reflex  nervous  mechanism  is  aided  by  a 
local  sensibility  of  the  iris  to  light.  In  these  animals  the  contraction 
of  the  pupil  in  response  to  illumination  takes  place  even  in  the  excised 
eye,  and  seems  to  be  determined  by  a  direct  stimulation  of  the  pig- 
mented contractile  fibres  of  the  sphincter  pupillsB  by  means  of  the 
light. 

The  effect  of  light  on  the  pupil  varies  considerably  according  to  the 
condition  of  adaptation  of  the  eye.  The  dilatation  of  the  pupil  is 
maximal  when  the  eye  has  been  in  the  dark  for  some  time  and  mav 
amount  then  to  7-3  to  8  mm.  In  one  experiment,  on  exposing  the 
eye  to  a  feeble  light,  e.g.  1-G  candles  at  a  moderate  distance,  the  pupil 
diminished  in  size  to  6-3  mm.  ;  with  an  illumination  of  50  to  100 
candles  the  size  of  the  pupil  was  3-7  mm.,  and  with  500  to  1000 
candles,  3-3  mm.  This  effect  was  obtained  by  a  rapid  change  of  the 
illumination  of  the  eye.  When  the  change  in  illumination  is  suffi- 
ciently slow  no  alteration  of  the  pupil  takes  place,  and  when  the 
illumination,  which  has  at  first  caused  a  maximal  constriction  of  the 
pupil,  is  continued  the  pupil  gradually  relaxes  with  the  adaptation 
of  the  retina  to  light.  This  relaxation  occurs  within  three  or  four 
minutes  after  exposure  to  light  has  taken  place.  The  same  influence 
of  adaptation  will  be  observed  if  two  individuals  are  brought  into  a 
moderately  lighted  room,  one  from  bright  daylight  and  the  other 
from  a  dark  room.  The  pupils  of  the  first  will  dilate  widely,  while 
those  of  the  second  will  constrict  to  their  maximum  extent.  In 
each  case  the  change  will  pass  off  gradually,  so  that  at  the  end  of 
five  or  ten  minutes  there  will  be  no  difference  observable  between 
the  eyes  of  the  two  persons. 

(2)  When  vision  is  directed  to  a  near  object  the  contraction  of 
the  ciliary  muscle  which  results  in  accommodation  is  accompanied 
with  convergence  of  the  visual  axes,  brought  about  by  contraction 
of  the  two  internal  rectus  muscles.  With  these  two  movements 
is  always  associated  a  third,  viz.  contraction  of  the  sphincter  pupilljB, 
the  increased  sharpness  of  the  image  obtained  by  this  means  being  an 


614  PHYSIOLOGY 

indispensable  condition  for  the  fineness  of  vision  which  we  desire 
when  we  examine  any  object  closely.  The  fact  that  the  amount 
of  light  which  will  fall  into  the  eye  from  any  given  object  increases 
inversely  as  the  square  of  the  distance  of  the  object  from  the  eye  ensures 
that  sufiicient  light  will  pass  through  the  constricted  pupil  for  the 
appreciation  of  the  finer  details  of  the  object. 

(3)  In  sleep  the  pupils  are  always  contracted.  This  fact  seems 
at  first  in  opposition  to  the  other  conditions  regulating  the  size  of 
the  pupil,  since  during  sleep  no  light  is  falling  into  the  eye.  If  the 
eyelid  of  a  sleeping  person  be  raised  the  pupil  will  be  found  to  be 
constricted  ;  as  the  person  wakes  up,  in  consequence  of  the  inter- 
ference, the  pupil  dilates  and  may  then  constrict  again  if  the  light 
is  held  so  as  to  fall  into  the  eye.  This  behaviour  of  the  pupil  may 
enable  us  to  distinguish  feigned  from  real  sleep.  The  constriction  of  the 
pupil  is  really,  like  that  which  accompanies  accommodation,  an 
associated  condition,  and  depends  on  the  fact  that  during  sleep  the 
axes  of  the  eyeballs  are  directed  upwards  and  inwards. 

(4)  Contraction  of  the  pupil  is  a  marked  effect  of  the  action  of 
certain  drugs,  especially  opium  and  its  alkaloid,  morphia,  as  well  as 
of  the  alkaloids  eserine,  or  physostigmine,  and  pilocarpine.  Contrac- 
tion of  the  pupil  also  occurs  in  general  excitatory  conditions  of  the 
central  nervous  system  and  is  therefore  found  during  the  stage  of 
induction  of  chloroform  and  ether  anaesthesia. 

Dilatation  of  the  fupil  occurs  : 

(1)  On  the  removal  of  light  stimulus  from  the  eye.  If  the 
removal  is  complete  the  pupil  remains  dilated,  but  if  there  is  any 
light  at  all  the  pupil  gxadually  constricts  again  as  the  eye  becomes 
dark-adapted. 

(2)  Dilatation  of  the  pupil  can  be  reflexly  excited  by  the  stimula- 
tion of  many  sensory  nerves,  and  is  constantly  observed  as  a  result 
of  severe  pain.  The  presence  or  absence  of  dilated  pupils  may  serve 
therefore  as  a  means  of  testing  how  far  an  emotional  expression  of 
pain  is  to  be  credited  to  a  physical  cause. 

(3)  The  pupils  are  often  dilated  in  emotional  conditions  such  as 
fear. 

(4)  Dilatation  of  the  pupils  occurs  in  every  condition  of  extreme 
exhaustion,  when  the  activities  of  the  nervous  centres  are  lowered. 
It  is  therefore  seen  during  the  third  stage  of  chloroform  anaesthesia, 
or  in  the  comatose  condition  produced  by  excess  of  alcohol.  Among 
the  drugs  which  cause  dilatation  of  the  pupil  the  belladonna  alkaloids, 
atropine  and  homatropine,  are  the  best  known.  These  alkaloids  will 
produce  dilatation  of  the  pupil  when  simply  dropped  into  the  con- 
junctival sac,  and  are  therefore  largely  used  to  dilate  the  pupil  as  a 
preliminary  to  ophthalmoscopic  investigation  of  the  eye. 


DIOPTRir  MECHANISMS  OF  THE  EYEBALL 


01  n 


INNERVATION  OF  THE  INTRINSIC   MUSCLES   OF  THE   EYE 
The  eyeball  is  supplied  by  the  short  ciliary  nerves,  which  come 
from  the  lenticular  or  ciliary  ganglion  and  passing  forwards  pierce  the 
sclerotic  coat  about  half-way  between  the  anterior  and  posterior  poles 
of  the  eyeball.    The  lenticular  gan- 
glion has  three  so-called  roots,  by 
which  it  is  connected  with  or  receives 
fibres  from  : 

(1)  The  third  or  oculo-motor 
nerve,  by  the  '  short  root.' 

(2)  With  the  sympathetic  plexus 
lying  in  the  cavernous  sinus,  and, 
through  the  fibres  lying  on  the 
internal  carotid  artery,  with  the 
cervical  sympathetic  nerve. 

(3)  With  the  nasal  branch  of  the 
ophthahnic  division  of  the  fifth  nerve 
by  means  of  the  '  long  root.' 

The  eyeball  is  also  supplied  by  l.c 
the  two  long  ciliary  nerves  (Fig.  276) 
which  come  direct  from  a  branch  of 
the  ophthalmic  division  of  the  fifth 
nerve  and  pass  forwards  on  to  the 
eyeball,  piercing  the  sclerotic  coat 
in  front  of  the  point  at  which  this 
coat  is  penetrated  by  the  short 
ciliary  nerves.  There  are  thus  three 
nerves  by  means  of  which  the 
activity  of  the  muscular  fibres  form- 
ing the  ciliary  muscle,  the  sphincter, 
and  the  dilatator  iridis  can  be  in- 
fluenced, viz.  the  third   nerve,  the 


OC.771 


Fig.  276. 


V.ojith 


Nerve-supply  to  the  eyeball. 
(After  Foster.) 
l.g,  lenticular  ganglion  with  its  three 
roots,  viz.  :    r.h,   radix   brevis  or  short 
root  ;    r.l,   radix  longus  or    long   root ; 
sum,  sympathetic  root  ;     V.   opth.  oph- 
fifth    nerve,    and    the    sympathetic    tiiahuic  division  of  V  nerve  ;    ///  ocm, 
^  ...         , ,  ,      !•   .  I        oculo-motor    nerve  ;    //,    optic    nerve  ; 

nerve.      On  excitmg  the  root  ot  the   ic,    long    cUiary    nerves ;      s.c,    short 
third  nerve  we  obtain  :  ciliary  nerves, 

(a)  Constriction    of    the    pupil. 

(6)  Contraction  of  the  ciliary  muscle,  i.e.  spasm  of  accommoda- 
tion. 

The  same  effects  are  produced  by  stimulating  the  lenticular  ganglion 
or  the  short  ciliary  nerves. 

Excitation  of  the  long  ciliary  nerves  of  the  ophthalmic  division  of 
the  fifth  nerve,  or  of  the  Gasserian  ganglion,  causes  dilatation  of  the 
j)upi].  but  is  without  iiiHuciu-e  on  the  ciliary  muscle. 


616  PHYSIOLOGY 

Stimulation  of  the  sympathetic  in  the  neck  causes  maximal  dilata- 
tion of  the  pupil  accompanied  by  constriction  of  the  vessels  of  the 
iris  and  the  eyeball  generally.  If  the  superior  cervical  ganglion 
be  extirpated  so  as  to  cause  degeneration  of  all  the  sympathetic 
fibres  passing  up  to  the  eye,  it  will  be  found  a  fortnight  later  that 
stinmlation  of  the  Gasserian  ganglion  has  no  longer  any  influence  on 
the  size  of  the  pupil.  We  may  therefore  come  to  the  following  con- 
clusions as  to  the  functions  of  the  nerves  supplying  the  interior  of 
the  eyeball : 

The  third  nerve  supplies  fibres  which  run  through  the  lenticular 
ganglion  and  the  short  ciliary  nerves  and  cause  constriction  of  the 
pupil  and  contraction  of  the  ciliary  muscle.  These  fibres  arise  in  the 
oculo-motor  nucleus,  which  is  situated  at  the  back  part  of  the  floor 
of  the  third  ventricle,  immediately  below  the  anterior  corpora  quadri- 
gemina. 

The  sympathetic  nerve  sends  fibres  which  pass  to  the  eye  along 
two  routes.  A  certain  number  which  run  on  the  external  carotid 
artery  in  the  cavernous  sinus  pass  by  the  sympathetic  root  to  the 
ganglion  and  by  the  short  ciliary  nerves  to  the  eyeball  and  cause 
contraction  of  the  blood-vessels.  Other  fibres  pass  from  the  superior 
cervical  ganglion  to  the  Gasserian  ganglion  of  the  fifth  nerve,  along  the 
nasal  branch  of  its  first  division  and  then  along  the  long  ciliary  nerves 
to  the  eyeball.  These  fibres  carry  impulses  which  dilate  the  pupil. 
The  sympathetic  fibres  to  the  eyeball  arise  in  the  cord,  probably 
from  cells  of  the  lateral  column  in  the  lower  cervical  or  uppermost 
dorsal  region.  They  leave  the  cord  by  the  first  two  dorsal  anterior 
roots,  pass  through  the  stellate  ganglion,  the  ansa  Vieussenii,  and  up 
the  cervical  sympathetic  to  the  superior  cervical  ganglion  where  they 
terminate.  New  relays  of  fibres  start  in  this  ganglion  and  travel 
direct  to  their  destination  in  the  eyeball.  Excitation  of  the  cervical 
spinal  cord  easily  evokes  dilatation  of  the  pupil,  and  it  was  on 
this  account  that  Budge  located  in  this  part  of  the  cord  a  cilio-spinal 
centre. 

The  fibres  derived  from  the  fifth  nerve  itself  must  be  looked  upon 
as  chiefly  afferent  or  sensory  in  function.  Some  observers  have 
ascribed  to  them  a  dilatator  effect  on  the  blood-vessels  of  the  eye,  but 
confirmation  for  this  view  is  wanting.  The  ciliary  muscle  is  normally 
at  rest  and  is  only  set  into  activity  as  a  result  of  volitional  or  reflex 
efforts  to  direct  the  gaze  to  near  objects.  The  iris  is  under  the  influ- 
ence of  tonic  impulses  which  arrive  at  it  along  both  sets  of  nerve 
fibres,  oculo-motor  and  sympathetic.  Section  therefore  of  the  sym- 
pathetic nerve  causes  constriction,  and  section  of  the  third  nerve 
dilatation  of  the  pupil.  These  tonic  influences  are  probably  reflex  in 
origin,  since  it  is  found  that,  after  cutting  off  afferent  impressions  from 


DIOPTRIC  MECHANISMS  OF  THE  EYEBALL 


cr 


the  retina  by  division  of  the  optic  nerve,  section  of  the  third  nerve 
produces  no  further  dilatation  of  the  pupil. 

Since  the  dilatator  muscle  is  often  difficult  to  demonstrate  under  the  micro- 
scope, the  view  has  been  put  forward  that  dilatation  of  the  pupil  on  stimulation 
of  the  sympathetic  nerve  is  due  merely  to  the  relaxation  of  the  tonic  contraction 
of  the  sphincter  pupillset  The  following  experiments  by  Langley  and  Anderson 
showed  definitely  the  erroneousness  of  this  view: 

On  stimulating  the  corneo-sclerotic  jmiction  so  as  to  excite  a  limited  portion 
of  the  iris,  a  well-defined  local  dilatation  of  the  pupil  is  produced.  If  the 
dilatation  were  due  to  the  relaxation  of  the  sphincter,  the  dilatation  could  not 
be  local,  but  would  have  extended  to  the  whole  circumference  of  the  pupil 


Fig.  277.     Effect  on  iris  of  cat  of  local  .stimulation. 
The  first  effect,  as  in  A,  is  to  cause  contraction  of  the  constrictor  pupillae 
below  the  electrodes,  and  this  is  succeeded  in  B  by  a  strong  localised  con- 
traction of  the  radiating  fibres.    (Langley  and  Anderson.) 

(Fig.  277).  In  another  experiment  they  isolated  a  sector  of  the  iris  by  two 
radial  cuts  ;  on  exciting  this  sector  it  .shortened,  and  the  same  effect  was  pro- 
duced by  excitation  of  the  sympathetic  in  the  neck,  although  any  action 
of  the  sphincter  must  have  been  abolished  by  the  mode  of  preparation. 
Section  of  the  sympathetic  in  the  neck  causes  lasting  constriction  of  the 
pupil,  and  the  same  effect  is  produced  by  extirpation  of  the  superior  cervical 
ganglion.  After  the  lapse  of  some  time,  however,  the  muscles,  freed  from  their 
nervous  connections  with  the  ganglion,  enter  easily  into  a  condition  of  lu-per- 
tonus,  so  that  the  pupil  on  the  side  of  the  lesion  may  be  more  dilated  than  on 
the  normal  side.  This  hji^ertonus  is  especially  marked  when  a  slight  anunnit 
of  asphyxia  or  rise  of  blood  pressure  is  present. 

THE  OPHTHALMOSCOPE 

By  means  of  this  instrument  we  are  enabled  to  obtain  a  magnified  picture 
of  the  back  of  the  eyeball,  as  well  as  to  judge  of  the  presence  and  degree  of 
abnormalities  in  the  refracting  apparatus  of  the  observed  eye. 

When  light  falls  on  the  eye  through  tlie  pu])!!  tlie  greater  part  of  it  is  absorbed 


618 


PHYSIOLOGY 


by  the  pigment  of  the  retina  and  the  choroid  coat.  A  small  amount,  however, 
is  diffusely  reflected,  and  is  sent  out  by  the  way  it  came,  viz.  through  the  pupil. 
If  the  vision  is  directed  on  the  luminous  point  at  the  source  of  the  rays,  the 
reflected  rays  leaving  the  eye  will  be  converged  to  a  point  and  form  an  image 
which  will  coincide  with  the  source  of  illumination.  It  is  on  this  account  that 
the  pupil  always  appears  black.  When  we  look  at  a  person's  eye,  we  necessarily 
interpose  our  head  and  eye  between  the  observed  eye  and  the  source  of  light, 
so  that  no  reflected  light  can  come  back  to  our  eyes.  Only  in  albinos,  where 
the  pigment  of  the  choroid  coat  and  retina  is  lacking,  do  we  get  a  red  appear- 
ance, due  to  the  reflected  light  passing  through  the  vascular  tissues  of  the 
choroid  and  iris. 


Fig.  278.     Indirect  ophthalmoscopy. 

A,  course  of   rays  from  source  of  light  E  to  observed  eye  ;  o,  observer's 
eye  ;    m,  mirror  ;    L,  lens. 

B,  course  of  rays  from  an  illuminated  spot  on  the  retina  of  the  observed 
eye  to  the  observer's  eye. 


In  a  hypermetropic  eye  at  rest  only  those  rays  are  brought  to  a  focus  on  the 
retina  which  are  convergent  as  they  enter  the  pupil.  Light  reflected  from 
the  retina  of  such  an  eye  will  therefore  be  divergent  as  it  leaves  the  pupil, 
and  we  may  obtain  a  '  red  reflex  '  by  direct  observation  of  the  eye. 

In  order  that  we  may  obtain  an  image  of  the  interior  of  a  normal  eye  we  must 
arrange  that  our  eye  comcides  with  the  source  of  illumination.  For  this  purpose 
we  use  the  device  invented  by  Helmholtz,  viz.  a  slightly  concave  mirror  with 
a  hole  in  the  centre.  By  means  of  this  mirror  light  is  converged  on  to  the  pupil, 
and  the  light  reflected  by  the  retina  is  brought  to  a  focus  at  the  centre  of  the 
mirror,  where  is  placed  the  observer's  eye.  This  ophthalmoscope  may  be 
used  in  one  of  two  ways  : 

(a)  INDIRECT  OPHTHALMOSCOPY.  In  carrying  out  ophthalmic  observa- 
tions the  examination  is  much  faciUtated  by  instilling  atropine  into  the  observed 
eye,  so  as  to  dilate  the  pupil  to  the  widest  extent  and  paralyse  the  mechanism 
of  accommodation.  If  a  beam  of  light  be  thrown  into  the  pupil,  the  emergent 
rays  from  the  eye  will  be  parallel,  and  will  give  rise  to  a  red  reflection  seen  by 


DIOPTRIC  MECHANISMS  OF  THE  EYEBALL  019 

the  observer's  eye  at  the  centre  of  the  ophthalmoscopic  mirror.  If  the  eye 
be  myopic,  the  issuing  rays  will  be  convergent  and  \nll  therefore  be  brought 
to  a  focus  at  some  point  in  front  of  the  eye,  giving  rise  to  a  real  image 
of  the  retina.  If  the  eye  be  hypermetropic,  the  issuing  rays  will  be 
divergent,  and  the  observer  will  see  the  red  reflection  of  light  from  the  back 
of   the  retina. 

If  now  a  len.s  of  low  power,  say  about  ten  dioptres  (4  in.  focus),  be  held  a  few 
centimetres  in  front  of  t\w  observed  eye  (Fig.  278b),  the  reflected  rays  issuing 
from  the  pujiil  will  be  brought  to  a  focus  at  a  point  between  the  observer  and  the 
lens,  .so  that  at  thi.«  point  will  be  formed  a  real  inverted  image  of  the  back  of 
the  eyeball.  Tliis  image,  in  the  case  of  the  normal  eye,  will  lie  at  the  focus  of 
the  lens.  If  the  eye  be  myopic,  the  convergent  rays  will  be  brought  to  a 
focus  nearer  to  the  lens  than  its  principal  focus,  while  the  divergent  rays  from 
the  hypermetropic  eye  will  give   rise   to   an   image   in   a   plane   between   the 


p        ^ 

1                                      r^''\^ 

^.^^-^ 

i^^i^^ 

0              A 

6V         y^ 

Fig.  279.  To  illustrate  how  the  rays  from  an  illuminated  point  of 
the  retina  form  a  parallel  beam  on  leaving  the  eye,  and  are 
brought  to  a  focus  at  B  by  interposing  the  lens  L. 

principal  focus  and   the   observer.      From   the   figure    (Fig.  279)  it  is   evident 

that    —  =    — ,  i-e.  the  magnification  of  the  image  will   be  proportional  to 

AB         AO 
the  focal  length  of  the  lens  used  divided  by  the  posterior  focal  length  of  the 
eyeball.     If  we  are  using  a  bi-convex  lens  of  10  cm.  focal  length  and  the  eye 
be  assumed  to  have  a  posterior  focal  length  of  l-ocm.,  the  real  inverted  image 

10 
that  we  see  in  front  of  the  bi-convex  lens  wll  be  r-^.  i.e.  6-7  times  as  large  as 

lo 

the  retinal  structures  represented. 

(b)  THE  DIRECT  METHOD.  In  this  method  the  observer  places  himself 
close  to  the  observed  eye,  throAving  light  into  the  latter  from  the  mirror,  and 
relaxes  by  an  effort  of  will  his  accommodation  absolutely.* 

If  both  the  observer's  eye  and  the  observed  eye  are  normal  and  unaccom- 
modated, i.e.  focused  for  distance,  the  rays  of  light,  issuing  from  any  point 
on  the  retina  of  the  observed  eye,  will  leave  the  corneal  surface  as  a  beam  of 
parallel  rays,  which  on  entering  the  observing  eye  will  in  turn  be  focused  to 
a  point  on  its  retina.  The  observer  therefore  sees  an  erect  magnified  image 
of  the  retina  of  the  observed  eye.  If  we  take  the  focus  oftne  eye  as  1-5  cm, 
the  magnification  of  the  image  is  eqmvalent  to  that  which  would  be  produced 

20 
by  a  lens  of  the  same  focus  and  is  equal  to  y-L,  t.e.  about  thirteen  times,     bince 

*  In  the  use  of  the  ophthalmoscope  it  is  very  difficult  to  relax  accommodation 
M'hen  trying  to  .see  something  which  is  quite  close.  The  student  will  fijid  it 
an  advantage  to  try  to  imagine  that  he  is  looking  through  a  telescope  at  an 
object  at  a  considerable  distance  ofF.  He  will  then  find  the  picture  at  the  back 
of  the  ('y«'ball  suddenly  come  into  view. 


620 


PHYSIOLOGY 


Fig.  280. 


Path  of  ra}\s  in  examination  by  the 
direct  method. 


this  method  gives  us  a  highly  magnified  image  of  the  back  of  the  eyeball,  it  is 

of  extreme  value  in  judging  of  the  existence  of  pathological  conditions  of  the 

retina  or  choroid.  It  is  also 
of  value  in  enabling  the  ocu- 
Ust  to  determine  by  objective 
methods  the  existence  of  any 
errors  of  refraction  in  a 
patient's  eye.  On  examining 
the  eye  by  the  direct  method, 
if  the  eye  be  myopic  and  the 
rays  leaving  it  convergent,  it 
win  be  impossible  for  the 
observing  eye  to  bring  them 
to  a  focus,  and  it  will  be 
necessary  to  place  a  concave 
lens  in  front  of  the  hole  in  the 
ophthalmoscopic  mirror  in 
order  to  bring  the  back  of 
the  observed  eyeball  into 
view.  The  weakest  divergent 
lens  through  which  an  image 
of  the  observed  eye  can  be 
obtained  will  give  the  degree 
of  myopia  of  the  eye.     On  the 

A,  path  of  illuminating  rays  ;   b,  path  of  rays  from    other  hand,  the    rays    from  a 
illuminated  retina  to  observer's  eye.  hypermetropic   eye,    being   di- 

vergent,   will    need    a    certain 

effort  of  accommodation  to  bring  them  to  a  focus  in  the  observer's  eye,  and  here 

the  degree  of    hypermetropia    will    be    given    by    the    focus    of    the   strongest 

convex    lens    through 

which  it  is    just  pos-  eg 

sible  to  obtain  a  clear 

image    of    the  retina 

and    retinal     vessels. 

By  the    same    means 

we  may  judge  of  the 

existence  of  astigma- 
tism and  form  an  idea 

of    the    meridians    in 

which    the    refractive 

power    of    the  eye  is 

faulty.    For  this  pur- 
pose observations  are 

taken  of  the  focus  of 

the    eye — firstly,    for 

horizontal      retinal 

vessels ;  secondly,  for 

vessels  which  are  run- 
ning vertically.  j'jfj 
On  examining  the 

back    of    the   eyeball 

by    either    of     these 

methods,  the  most  prominent  object  is  the  optic  disc  or  optic  nerve-papilla, 

which  marks  the  point  of  entrance  of  the  optic  nerve.     It  is  seen  as  a  pale  oval 


281.  Ophthalmoscopic  view  of  fundus  of  eye,  showing 
the  optic  disc,  or  point  of  entry  of  the  optic  nerve, 
with  the  retinal  vessels  branching  from  its  centre. 


DIOPTRIC  MECHANISMS  OF  THE  EYEBALL  021 

disc  surrounded  by  a  deep  red  background  (Fig.  281).  From  the  middle  of  the 
papilla  the  retinal  vessels  pass  into  the  eyeball,  and  they  are  seen  diverging  from 
the  papilla  to  ramify  over  the  rest  of  the  retina.  The  arteries  can  be  distin- 
guished from  the  veins  by  their  brighter  red  colour  as  well  as  by  the 
stronger  reflection  of  light  from  their  surfaces.  The  yellow  spot  is  very 
difficult' to  see,  except  in  atropinised  eyes,  since  it  only  comes  into  view 
when  the  observed  ej'e  is  looking  straight  into  the  ophthalmoscope.  Under 
these  conditions  there  is  a  strong  '  light  reflex,'  and  the  pupil  contracts  up 
to  a  pin-point,  unless  paralysed  by  means  of  atropine.  In  order  to  see 
the  blind-spot,  or  optic  disc,  the  observed  e3'e  must  be  directed  inwards  ;  thus 
if  A  is  looking  at  the  right  eye  of  B,  B  must  be  told  to  look  over  A's  right 
shoulder. 


SECTION  VII 

THE   RETINAL   CHANGES  INVOLVED   IN    VISION 

In  nearly  all  sense-organs  the  essential  constituent  is  a  bipolar 
nerve- cell  having  one  process  extending  towards  the  surface  and 
ending  between  epithelium-cells  covering  that  surface,  and  a  central 
process,  which  runs  towards  the  central  nervous  system,  where  it  forms 
synapses  with  the  processes  of  other  nerve-cells  (Fig.  282).  In  some 
cases,  such  as  the  oHactory  cells  and  the  sense-cells  embedded  in  the  epi- 


A  B  C  D 

Fig.  282. 
A,  olfactory  sense-cell ;    B,   auditory  sense-cell ;    c,   connections  of 
gustatory    fibres     (taste-bud)  ;    D,    nerve-ending    in    skin    or    corneal 
epithelium  (probably  pain  fibres). 

dermis  of  worms  and  other  invertebrata,  the  peripheral  process  is  quite 
short.  In  other  cases,  as  in  the  ordinary  posterior  root  ganglion-cell, 
the  peripheral  process  may  be  several  feet  in  length.  The  retina, 
however,  cannot  be  regarded  as  a  simple  sense-organ,  but  is  homologous 
with  a  complete  lobe  of  the  brain.  It  is  formed,  like  the  cerebral  hemi- 
spheres, as  a  hollowed  outgrowth  from  the  fore-brain  or  anterior  cere- 
bral vesicle.  The  stalk  of  this  outgrowth  narrows  so  as  to  produce  an 
optic  vesicle  connected  with  the  rest  of  the  fore-brain  by  the  optic  stalk. 
As  the  vesicle  grows  towards  the  surface  its  anterior  wall  is  invaginated 
so  that  an  '  optic  cup  '  is  formed,  at  the  mouth  of  which  the  lens  and 
other  parts  of  the  eye  are  developed  at  the  expense  of  the  over-lying 
epiblast  and  the  surrounding  mesoblast.  The  posterior  wall  of  the  cup 
develops  into  the  retin^il  pigment,  while  the  nervous  elements  which 

622 


RETINAL  0HANGE8  INVOLVED  IX  VISKJN 


623 


make  up  the  retina  are  formed  by  division  and  differentiation  from 
the  anterior  wall.  That  part  of  the  cup  originally  derived  from  the 
external  surface  of  the  body  is  turned  towards  the  posterior  layer 
or  retinal  pigment.  From  it  is 
developed  the  special  end-organ  of 
vision,  viz.  the  rod  and  cone  layer 
of  the  retina.  Besides  this  special 
sensory  epithelium,  the  retina  pre- 
sents two  other  sets  of  neurons 
through  which  impulses  generated 
in  the  sensory  epithelium  must  pass 
before  they  arrive  at  the  optic  nerve. 
The  three  relays  of  nervous  elements 
in  the  retina  have  the  following 
arrangement : 

(1)  The  first  relay — the  sense 
epithelium — consists  of  rods  and 
cones  with  their  nuclei  (Fig.  283), 
the  latter  being  situated  in  the 
outer  nuclear  layer.  Each  rod  pre- 
sents an  external  (a)  and  an  internal 
limb  (6).  The  former,  in  the  eye 
which  has  been  kept  in  the  dark, 
has  a  purplish  colour  from  the  pre- 
sence of  rhodopsm  or  visual  purple. 
From  the  inner  end  of  the  inner 
limb  a  fine  fibre  c  passes  to  its 
nucleus  in  the  outer  nuclear  layer, 
and  from  the  nucleus  a  central 
process  g  passes  into  the  outer 
molecular  layer  where  it  ends  freely 
in  a  little  knob  e.  The  cones, 
which  are  thicker  than  the  rods, 
also  possess  outer  and  inner  limbs. 
From  the  inner  limb  a  thick  process, 
containing  a  nucleus,  passes  through 
the  external  nuclear  layer  and  ends 
with   a   broad   base  e  in  the  outer 

molecular  layer,  from   which  short  fibres  are  given  oft'  to  come  in 
contact  with  the  bipolar  cells  of  the  inner  nuclear  layer. 

(2)  The  second  relay  is  formed  by  the  bipolar  cells  of  the  inner 
nuclear  layer.  Each  of  these  sends  off  one  fibre  peripherally  to 
make  contact  with  endings  of  the  rod  and  cone  fibres  in  the  outer 
molecular  la^^er,  and  another  process  which  passes  centrally  into  the 


Fig.  283. 
I,  a  rod  ;  ii.  a  eono  of   niaininalian 
ntina  ;     /;,   oxternal    limiting    nuMii- 
brane.     (R.  (Iroeff.) 


624 


PHYSIOLOGY 


inner  molecular  layer.  Here  the  process  of  the  rod  bipolar  forms  an 
arborisation  around  the  body  of  a  cell  in  the  ganghon-cell  layer,  while 
the  processes  of  the  cone  bipolars  end  at  various  levels  in  the  inner 
molecular  layer,  forming  synapses  with  the  dendrites  of  the  ganglion- 
cells. 

(3)  The  ganglion-cells,  which  represent  the  third  relay,  receive  the 
impulses  from  the  more  peripheral  parts  of  the  retina  and  send  them 
towards  the  brain  along  the  fibres  of  the  optic  nerve,  each  of  which 
is  the  axon  of  one  of  the  sanglion-cells.     These  axons,  which  form 


71.M. 


Fig.  284.     Schema  of  retina.    (From  Bohm  and  Davidoff  after  Cajal.) 
1,  nerve-fibre  layer  ;  2,  ganglion-cell  layer  ;    3,  inner  molecular  layer  ; 

4,  inner  nuclear  layer  ;  5,  outer  molecular  layer  ;    6,  outer  nuclear  layer  ; 

c,  cone  ;    r,   rod  ;    b,  bipolar  cells  ;    S,  spongioblast ;    am,  amacrine  cell ; 

c.n,  centrifugal  nerve  fibre ;    M,  fibre  of  Miiller  ;   n.M,  nucleus  of  fibre  of 

Miiller  ;   n,  neuroglia  ;  o,  outer  limiting  membrane. 

the  inner  layer  of  the  retina,  the  so-called  '  nerve-fibre  layer,'  are 
non-medullated  as  they  pass  over  the  surface  of  the  retina,  but  acquire 
a  medullary  sheath  as  they  pass  out  of  the  eyeball  through  the 
cribriform  plate  of  the  sclerotic  and  join  to  form  the  optic  nerve. 

Most  of  the  bipolar  cells  are  connected  with  several  rods  or  cones  ; 
only  in  the  fovea  centraUs  do  .we  find  a  special  bipolar  cell  provided 
for  every  cone.  Every  ganglion-cell  comes  into  connection  with 
and  receives  the  impulses  from  a  considerable  number  of  bipolar  cells, 
so  that  the  number  of  fibres  in  the  optic  nerve  running  centrally  is  not 
so  great  as  the  number  of  sense  elements  in  the  rod  and  cone  layer 
of  the  retina.  Besides  these  cells  situated  on  the  direct  path  of  the 
visual  impulse,  other  cells  of  a  nervous  nature  are  found  in  the  inner 
nuclear  layer  (the  outer  and  inner  horizontal  cells),  and  also  in  the 


RETINAL  CHANGES  INVOLVED  IN  VISION 


625 


inner  molecular  layer,  the  so-called  '  amacrine  '  cells.  These  cells 
have  been  imagined  to  serve  as  a  means  of  connection  or  association 
between  different  parts  of  the  retina,  and  may  be  taken  as  analogous 
to  the  association-cells  found  in  the  cerebral  cortex.  The  analogy  of 
the  retina  with  a  lobe  of  the  brain  is  illustrated  by  the  fact  that,  in 
addition  to  the  fibres  originating  in  the  retina  and  passing  towards  the 
brain,  a  considerable  number  of  fibres  pass  from  the  central  nervous 
system  into  the  retina,  where  they  end  chiefly  in  the  two  molecular 
layers.     These  may  have  as  one  of  their  functions  the  correlation 


"$    '■a 


Fig.  285.     Section  through  half  the  fovea  centralis.    (Sciiafer 
and  GoLDiNG  Bird.) 


of  processes  occurring  in  the  retinae  of  the  two  eyes  and  may  be 
associated  with  phenomena  such  as  those  of  binocular  contrast,  which 
we  shall  have  to  study  later  on. 

Important  differences  are  found  in  the  structure  of  the  retina 
in  its  different  parts.  At  the  point  of  entrance  of  the  optic  nerve 
— the  oftic  disc — -the  only  elements  present  are  the  nerve  fibres,  which 
diverge  from  this  point  over  the  whole  inner  surface  of  the  retina. 
A  short  distance  externally  to  the  optic  disc  is  found  the  macula  lutea 
with  a  small  depression  in  the  middle,  the  central  spot  or  fovea  centralis 
(Fig.  285).  When  we  fix  our  gaze  on  any  object  the  visual  axes  are 
so  directed  that  the  image  of  the  object  falls  on  the  fovea  centralis. 
At  this  spot  the  retina  is  thinned  by  the  gradual  disappearance  of  all 
its  layers  except  the  outermost.  The  outermost  layer  is  moreover 
distinguished  by  the  fact  that  the  rods  have  disappeared  and  that 

40 


626  PHYSIOLOGY 

only  the  cones  are  present,  and  are  very  much  larger  than  the 
cones  in  any  other  part  of  the  retina.  The  fibres  from  those  cones, 
passing  to  the  inner  nuclear  layer,  diverge  as  they  leave  the  fovea 
centralis,  all  the  layers  of  the  retina  being  displaced  towards  the 
circumference  in  order  to  allow  the  light  to  fall  on  the  cones  without 
having  to  pass  through  any  of  the  other  layers  of  the  retina. 
As, we  pass  from  the  centre  to  the  periphery  of  the  retina  the 
cones  become  fewer  and  the  rods  more  numerous.  At  the  extreme 
margin  the  rods  also  are  scattered  more  diffusely,  and  at  the  ora  serrata, 
which  lies  a  short  distance  behind  the  ciliary  processes,  the  special 
nervous  elements  come  to  an  end,  and  the  retina  is  continued  forwards 
over  the  ciliary  processes  and  the  posterior  surface  of  the  iris  as  a  layer, 
two  cells  thick,  closely  packed  with  pigment  granules  (the  uvea). 

The  followino-  facts  show  that  the  laver  of    the  rods  and  cones 


Fig.  286. 

represents  the  end-organ  of  vision,  and  that  for  distinct  vision  to  take 
place  the  image  of  an  external  object  must  be  formed  in  this  layer  : 

(a)  The  point  of  entry  of  the  optic  nerve,  where  the  whole  thickness 
of  the  retina  is  composed  of  nerve  fibres,  is  absolutely  insensitive  to  fight 
and  constitutes  the  bfind-spot  (Fig.  286).  If  the  light  of  a  small  flame 
be  directed,  by  means  of  a  mirror,  into  the  eye  so  that  it  falls  only  on 
to  the  optic  disc,  the  individual  receives  no  sensation  of  fight.  The 
existence  of  the  blind-spot  is  more  easily  shown  by  the  following 
experiment  :  On  closing  the  left  eye  and  gazing  fixedly  with  the  right 
eye  at  the  white  cross  in  the  figure,  on  approximating  the  book  to  the 
eye  a  point  will  be  found,  when  the  book  is  at  a  distance  of  eight 
inches  from  the  eye,  at  which  the  white  circle  becomes  invisible  and 
the  whole  figure  appears  to  be  covered  by  the  black  ground.  By 
measuring  the  apparent  size  of  the  blind-spot  and  its  distance  from 
the  point  of  fixation,  we  find  that  its  situation  on  the  retina  corresponds 
exactly  to  the  point  of  entry  of  the  optic  nerve.  The  blind-spot  is  so 
large  that  at  a  distance  of  about  six  feet  the  image  of  the  head  of  a 
man  will  fall  on  it  and  therefore  be  invisible. 

(6)  At  the  point  of  most  distinct  vision,  i,e.  the  fovea  centralis,  al] 


RETINAL  CHANGES  INVOLVED  IN  VISION 


()27 


the  layers  of  the  retina  are  absent  except  the  outermost,  i.e.  that  of 
the   cones. 

(<?)  '  Purkinje's  fif(ures.'  If  a  stroiio;  Ijirht  be  focused  by  means  of 
a  lens  on  to  the  sclerotic  just  outside  the  cornea,  and  the  eye  be  made 
to  stare  fixedly  at  a  dull  blackground,  an  arborescent  image  of  the 
retinal  vessels  will  appear  on  the  background.  On  moving  the 
illumination  the  image  of  the  vessels  will  move  in  the  same  direction. 
Knowing  the  dimensions  of  the  eyeball  and  the  distance  of  the  back- 
ground from  the  eye  as  well  as  the  angle  through  which  the  light  is 
moved  and  the  apparent  displacement  of  the  image  of  the  vessels, 
the  distance  of  the  sensory  part  of  the 
retina  behind  the  vessels  may  be  calculated 
(Fig.  287).  Direct  measurements  in  this 
way  have  shown  that  the  distance  between 
the  vessels  and  the  sensitive  elements  of  the 
retina  must  amount  to  between  0-17  and 
0-36  mm.  Anatomical  measurements  of  the 
thickness  of  the  retina  show  also  that  the 
average  distance  between  the  vessels  and 
the  layer  of  rods  and  cones  varies  between 
0-2  and  0'3  mm.,  showing  that  it  is  in  this 
layer  that  the  actual  transformation  of  a 
light  stimulus  into  a  nerve  impulse  must 
take  place. 

On  spreading  out  the  retina  under  the 
microscope  and  looking  at  its  external 
surface  we  see  that  the  rods  and  cones 
form  a  sort  of  mosaic,  the  thicker  cones 
being  surrounded  by  the  smaller  circles 
representing  the  cross-sections  of  the  rods. 
Since  each  of  these  is  a  terminal  sense- 
element  the  image  thrown  by  the  dioptric 
mechanism  of  the  eye  on  to  the  retina  must 
be  converted  into  a  mosaic-like  expanse  of  small  isolated  pictures,  and 
our  impression  of  external  objects  must  in  every  case  be  formed  bv  a 
synthesis  of  the  elementary  sensations  produced  by  the  stimulation  of 
every  single  rod  or  cone  cell. 


h:  v. 


Fig.  287.  Uiaf;ram  of  the 
path  of  the  iay.s  of  light  in 
the  formation  of  Purkinje's 
figures. 

V  represents  a  retinal  vessel. 
When  this  is  illuminated  from 
A,  a  shadow  is  formed  on  the 
hinder  layers  of  the  retina  at 
a'.  This  is  projected  along  a 
line  passing  through  the  optic 
a.xis,  and  appears  to  come  from 
a  point  (rt")  on  the  wall.  On 
nu)ving  the  light  from  a  to  b, 
the  image  of  the  vessel  appears 
to  move  from  a"  to  h". 


DIRECT  AND  INDIRECT  VISION 
If  we  fix  our  attention  on  to  an  ()i)ject,  we  direct  our  eyes  so  that 
the  image  of  the  centre  of  the  object  falls  exactly  on  the  fovea  centralis 
of  each  retina.  The  diameter  of  the  central  spot  is  about  1  to  1-5  mm., 
which  corresponds  to  a  visual  angle  of  4°  to  6°.  This  angle  therefore 
represents  the  extent  of  the  visual  field  in  which  we  have  distinct  vision. 


628 


PHYSIOLOGY 


The  light  which  falls  into  the  eye  forms  an  image  of  external  objects 
which  extends  over  the  whole  of  the  retina.  The  sensations 
excited  by  the  stimulation  of  the  periphery  of  the  retina  are  much 
more  indistinct  than  those  excited  by  the  image  on  the  central  spot. 
The  appreciation  of  external  objects,  by  means  of  the  image  they 
throw  on -the  external  parts  of  the  retina,  is  spoken  of  as  indirect 
vision  in  contradistinction  to  direct  vision,  which  implies  fixation  of 
the  object  and  the  formation  of  an  image  of  it  on  the  fovea  centralis. 
The  whole  extent  of  the  objects  which  we  can  see  by  direct  and  indirect 

vision  is  spoken  of  as  the 
visual  field.  In  order  to  de- 
termine the  visual  field  we 
make  use  of  a  perimeter 
(Fig.  288). 

This  instrument  consists  of  a 
band  of  metal  forming  the  arc  of 
a  circle  of  about  35  cm.  radius. 
At  one  end  this  arc  is  fastened  to  a 
pillar,  and  can  be  turned  through 
the  axis  passing  through  the  pillar 
so  as  to  lie  in  various  meridians. 
At  the  centre  of  the  circle  is  another 
pillar,  which  provides  a  chin -rest, 
so  arranged  that  the  eye  of  the 
observed  person  lies  exactly  at  the 
centre  of  the  circle  at  the  top  of 
the  pillar.  At  the  point  roxind 
which  the  arc  rotates  is  a  small 
white  disc.  In  using  the  instru- 
ment the  person,  whose  field  of 
AHsion  is  to  be  determined,  places 
his  eye  at  the  top  of  the  pillar  and 
gazes  fixedly  at  the  white  disc  ; 
another  small  white  disc  is  then  moved  along  the  curved  arc  and  the  point 
noted  at  which  it  is  no  longer  visible,  while  the  observed  person  is  gazing 
fixedly  at  the  white  disc  on  the  axis  of  rotation.  The  arc  is  then  moved  20° 
and  the  same  experiment  carried  out,  and  this  is  continued  until  the  limit  has 
been  determined  in  every  meridian  of  the  visual  field.  The  rotating  arc  is 
graduated,  the  graduations  showing  the  visual  angles  subtended  by  any  portion 
of  the  arc.  As  the  readings  are  made  thcj^  are  marked  down  on  a  chart,  such 
as  that  shown  in  Fig.  289,  so  that  finally  a  graphic  representation  of  the 
visual  field  is  obtained.  The  visual  field  is  more  extensive  on  the  outer  than  on 
the  nasal  side  of  the  eye,  the  latter  being  contracted  by  the  cutting  off  of  some 
of  the  rays  falling  on  the  outer  side  of  the  retina  by  means  of  the  nose. 

Although  stimulation  of  the  peripheral  parts  of  the  retina  does  not 
give  us  much  idea  of  the  nature  of  the  things  we  are  looking  at,  yet 
it  is  of  great  importance  in  informing  us  of  the  relation  of  the  object 
which  is  the  immediate  point  of  attention,  to  its  surroundings.     It 
therefore  plays  a  great  part  in  regulating  the  movements  of  the  body. 


Fig.  288.     Priestley  Smith's  perimeter. 


RETINAL  CHANGES  INVOLVED  IN  VISION 


629 


Its  importance  will  be  at  once  appreciated  if  one  eye  be  closed 
and  the  stimulation  of  the  periplieral  parts  of  the  retina  in  the  other 
eye  be  excluded  by  allo\vin<j;  this  eye  only  to  look  through  a  tube. 
Although  we  can  then  see  the  objects  to  which  we  direct  our  gaze 
perfectly  distinctly,  we  find  that  on  trying  to  move  towards  any  given 
object  our  movements  are  uncertain  and  misdirected. 


CHEMICAL   AND  PHYSICAL  CHANGES   IN  THE   RETINA 
When  light  falls  on  the  retina  chemical  and  physical  changes 
take  place  ;    these  either  originate  or  accompany  the  transmutation 


xn 


Fig.  289.     Perimeter  chart  showing  the  field  of  vision  in  a  normal  (right)  eye. 

of  the  ether  vibrations  into  the  nerve  impulses,  which  ascend  the  optic 
nerve.  If  a  frog  that  has  been  in  the  dark  for  some  time  be  killed,  an 
eye  taken  out,  bisected,  and  the  retina  removed  and  examined  by  a 
weak  light,  it  will  be  found  that  this  latter  has  a  purplish- red  colour. 
On  microscopical  examination  this  colour  is  seen  to  be  confined  to  the 
outer  hmbs  of  the  rods.  After  a  very  short  exposure  to  dift'use  day- 
light the  colour  disappears.  The  colouring-matter  (rhodofsin)  may 
be  dissolved  out  by  means  of  a  solution  of  bile  salts.  The  purple-red 
solution  thus  formed  also  bleaches  rapidly  on  exposure  to  hght.  By 
means  of  this  rhodopsin  photographs  or  '  optograms  '  of  external 
objects  may  be  taken  on  the  retina.  The  rabbit's  eye  is  cut  out  and 
placed  in  front  of  a  window.  After  some  time  the  eye  is  bisected  and 
plunged  into  a  4  per  cent,  solution  of  alum,  which  partially  fixes  the 


630 


PHYSIOLOGY 


optogram,  and  an  inverted  picture  of  the  \Yindow  with  its  cross-bars 
is  obtained  on  the  retina. 

If  a  retina,  which  has  been  bleached  by  exposure  to  light,  be 
replaced  on  the  pigment  layer  lining  the  choroid,  in  a  short  time 
the  colour  will  be  restored.  On  examining  sections  through  the  retina 
it  is  found  that,  in  one  which  has  been  exposed  to  light,  the  cells  of 
the  layer  of  pigmented  epithelium  send  up  fine  processes  full  of  pig- 
mented granules  between  the  outer  limbs  of  the  rods.  In  an  eye  which 
has  been  kept  in  the  dark,  on  the  other  hand,  the  cells  of  the  pigment 
layer  are  quite  flat,  so  that  the  front  part  of  the  retina,  including  the 
rods  and  cones,  can  be  removed  without  any  difficulty  (Fig.  290). 


It, I 


Fig.  290.     Sections  of  the  frog's  retina. 
A,  kept  in  the  dark ;    b,  after   exposure  to  light,  showing  retraction  of 
the  cones,  and  protrusion  of  the  pigmented  epithelium  between  the  outer 
limbs  of  the  rods.    (Engelmaxn.) 

Thus  the  function  of  the  pigmented  epithelium  is  to  supply  visual 
purple  to  the  outer  limbs  of  the  rods  as  fast  as  the  pigment  already 
there  is  bleached  by  light.  It  might  be  thought  that  this  chemical 
change  was  the  active  agent  in  producing  excitation  of  the  optic  nerve 
fibres  ;  but  the  fact  that  in  the  fovea  centralis,*  the  region  of  most 
distinct  vision,  w^e  find  only  cones  which  contain  no  visual  purple 
indicates  that  this  chemical  process  is  not  essential  for  the  conversion 
of  light- waves  into  a  nervous  impulse.  When  light  falls  upon  the 
retina  the  cones  are  retracted,  and  lie  close  upon  the  external  limiting 
membrane  ;  whereas  in  an  eye  that  has  been  kept  in  the  dark  they 
extend  down  between  the  rods  as  far  as  the  pigmented  layer. 

The  falling  of  light  on  the  retina  is  also  accompanied  by  an  electrical 
change,  which  may  be  regarded  as  analogous  to  the  current  of  action  in 
nerve.     It  is,  however,  much  more  complicated  than  the  latter.     The 

*  According  to  Edridge  Green  \'i.sual  purple  diffuses  into  the  fovea  centralis, 
and  plays  an  essential  part  in  vision  as  a  sensitiser  of  the  cones. 


RETINAL  CHANGES  INVOLVED  IN  VISION 


(VM 


eyeball  ol'  the  fro*,'  led  off  fi-oin  its  anterior  and  posterior  surfaces  shows 
a  current  directed  in  the  eyeball  from  behind  forwards  (the  resting  or 
demarcation  current).     It  was  first  shown  by  Holmgren  that  this 


II. 


fflffliiliiiijiiiEuiiiiHmHiillliiiiiiiim^^^^ 


III. 


.     V             .!ti^:Iii    : 

^^^          A.>.B,,^    : 

~44'^^^^fl^Hm*^  ■ 

...,iil-'^^li^^ 

MMm' 

j^i., ;                      ■'■•■•'  i:^;.  ;■■■■  r  '  i                    ■ 

Mi!..       ,;.;:i;i;ii  miiiii  iibii-   .    -.      ^  ^.lljiilTi'j: 

Fig.  2i)l.     Electrical  variation  in  frog's  eye  as  recorded  by  the  string 

galvanometer.    (Eixthovkn  and  Jolly.) 
I,  on  e.\po.sure  to  a  single  flash  ;    II,  on   exposure   to  light  of  moderate 
duration  ;  III,  effect  on  a  light  eye  of  momentary  darkening. 

resting  current  undergoes  modification  when  light  is  allowed  to  fall 
on  the  eyeball.  Of  late  years  the  nature  of  this  modification  has  been 
studied  especially  by  Waller  with  the  galvanometer,  by  (iotch  with 
the  capillary  electrometer,  and  by  Einthoven  and  Jolly  with  the  string 
galvanometer.     The  nature  of  the  response  varies  according  to  the 


632 


PHYSIOLOGY 


strength  and  duration  of  the  stimulus,  and  to  the  condition  of  the  eye, 
whether  fatigued  or  fresh,  light-  or  dark-adapted.  A  typical  response 
to  a  momentary  flash  is  shown  in  Fig.  291,  I.  Within  a  very  short 
latent  period  after  the  incidence  of  the  flash,  i.e.  after  a  latent  period  of 
not  more  than  -01  sec,  there  is  a  small  short  negative  variation 
of  the  resting  cm-rent,  which  is  immediately  followed  by  a  large 
positive  variation,  i.e.  the  resting  current  is  increased.  This  is  followed 
immediately  by  a  diminution  and  then,  after  a  considerable  latent 


II. 


Fig.  292.     Diagrammatic  representation  of  the   reactions  to  light  of  the 
three  hypothetical  substances  a,  b,  and  c.     (Einthoven  and  Jolly.) 
I,  the  three  effects  showTi  separately ;  II,  the  three  effects  combined  to 
form  a  single  curve.     A  is  the  lighting  and  Ai  the  darkening  effect  of  the 
first  substance.     I,  light ;    d,  darkness. 

period,  by  a  second  slow  prolonged  increase  of  the  current.  When 
the  duration  of  the  stimulus  is  longer  the  moment  of  shutting  off 
the  light  is  seen  to  be  followed  immediately  by  a  second  positive  varia- 
tion. This  is  shown  in  Fig.  291,  II.  It  is  possible  to  obtain  this  response 
to  darkness  by  shutting  off  for  a  short  period  of  time  the  light  falling  into 
the  eye.  The  result  of  such  an  experiment  is  shown  in  Fig.  291,  III. 
Einthoven  and  Jolly  explain  these  results  by  the  assumption  that  three 
separate  processes  are  concerned  when  the  retina  is  stimulated.  For 
convenience  they  speak  of  the  changes  in  three  distinct  substances, 
A,  B,  and  c.  Of  these  a  reacts  more  rapidly  than  the  other  two,  and 
its  action  is  specially  marked  in  a  '  light '  eye,  appearing  almost 
isolated  on  sudden  darkening  of  short  duration  (a  flash  of  darkness). 
On  lighting,  it  develops  a  negative,  on  darkening  a  positive  potential 


RETINAL  CHANGES  INVOLVED  IN  VISION  633 

difference.  The  substance  b  reacts  less  rapidly  than  a.  On  lighting, 
it  develops  a  positive,  on  darkening  a  negative  potential  difference. 
Its  action  is  especially  marked  in  a  dark  eye  which  is  illuminated  for  a 
short  time  with  a  weak  light.  Substance  c  reacts  in  the  same  sense  as 
B,  but  much  more  slowly.  Its  action  is  wanting  in  a  completely  hght 
eye.  The  actions  of  these  three  substances  are  represented  diagram- 
matically  in  Fig.  292,  I.  and  11. 

It  is  interesting  to  note  that  the  latent  period  of  the  photo-electric 
reaction  agrees  with  the  latent  period  of  the  light  perception  of  the 
human  eye,  and  may  vary  from  -01  sec.  with  strong  stimuli  to  as  much 
as  2  sec.  with  very  weak  stimuli. 


SECTION  VIII 

VISUAL  SENSATIONS 

The  retinal  changes  which  we  have  just  described  as  occurring  in 
the  retina  on  exposure  to  light  give  us  very  little  information  as  to  the 
nature  and  conditions  of  the  physiological  activity  excited  in  this 
organ  by  the  physical  stimulus  of  Hght.  We  are  therefore  driven  to 
use  as  our  criterion  of  these  physiological  processes  the  changes  excited 
in  consciousness,  and  the  gTeater  part  of  our  knowledge  of  the  physiology 
of  vision  is  derived  from  examination  of  such  of  our  own  sensations  as 
have  their  primary  origin  in  the  retina.  How  far  these  sensations 
can  be  regarded  as  having  their  seat  in  the  retina,  how  far  they  are 
determined  by  physiological  changes  in  the  visual  and  adjacent 
portions  of  the  brain,  it  is  not  possible  to  say.  We  are  only  able  to  deal 
with  the  sensations  as  they  spring  ready  formed  into  our  consciousness. 

NATURE  OF  THE  STIMULUS 

The  word  '  light,'  as  employed  by  physicists,  imphes  a  particular 
kind  of  energy,  which,  arriving  at  the  retina  in  a  certain  way,  excites 
in  us  a  sensation  of  light.  The  conception  is  therefore  primarily 
physiological.  Every  material  substance  is  endowed  with  a  certain 
amount  of  internal  energy,  the  index  to  which  is  its  temperature.  In 
virtue  of  this  energy  it  is  constantly  radiating  energy  at  a  greater  or 
less  rate  through  the  surrounding  ether,  its  internal  energy  at  any 
given  moment  being  determined  by  the  balance  between  the  amount 
of  energy  it  gives  off  and  the  amount  of  energy  which  it  receives  from 
surrounding  bodies.  This  radiant  energy  is  transmitted  through  space 
as  transverse  oscillations  of  the  ether  at  the  rate  of  about  two  hundred 
thousand  miles  per  second  and  with  very  variable  wave-length  and  rate 
of  oscillation.  The  whole  energy  available  to  us  on  the  surface  of  the 
earth  is  derived  from  that  portion  of  the  radiant  energy  of  the  sun  which 
is  intercepted  by  the  earth. 

Since  the  velocities  of  transmission  of  rays  of  various  wave-lengths 
differ  as  these  rays  pass  through  a  dense  medium,  such  as  glass,  it  is 
possible  to  break  up  the  compound  waves  of  radiant  energy  arriving 
at  us  from  the  sun,  or  emitted  by  any  hot  body,  by  allowing  them  to  pass 
through  a  prism.  When  the  luminous  solar  rays  are  passed  in  this 
way  through  a  prism  we  get,  as  is  known,  a  spectrum,  the  rays  which 

634 


^^SUAL  SENSATIONS  635 

are  refracted  the  least  being  red,  while  those  which  are  most  refracted 
are  blue.  Between  these  two  extremes  we  have  rays  of  the  following 
colours — orange,  yellow,  green,  blue,  indigo,  which  merge  one  into 
the  other  without  any  perceptible  break.  The  different  parts  of  the 
visible  spectrum,  when  obtained  from  the  sun,  show  vertical  dark 
lines,  which  are  known  as  Framihofer's  lines.  These  are  due  to  the  fact 
that  certain  rays  emitted  by  the  glowing  centre  of  the  sun  are  absorbed 
in  passing  through  the  gaseous  envelope  which  surrounds  the  sun.  The 
lines  are  distinguished  by  certain  letters  and  have  all  been  assigned  to 
the  existence  of  known  elements  in  a  gaseous  form  in  the  solar  envelope. 
Any  part  of  the  spectrum  is  distinguished  according  to  its  relation 
to  these  lines,  since  each  of  them  has  a  constant  wave-length.  The 
visible  spectrum  extends  from  the  line  A  at  the  limit  of  the  red,  which 
has  a  wave-length  of  760  millionths  of  a  millimetre,  to  the  line  H 
at  the  end  of  the  violet  with  a  wave-len,gth  of  397.  The  \nsible  part 
of  the  spectrum  does  not,  however,  include  even  the  majority  of  the 
rays  which  arrive  at  the  earth  from  the  sun.  Beyond  the  red  we  get 
the  ultra-red  rays,  which  have  a  large  amount  of  energy,  so 
that  their  presence  can  be  easily  detected  by  their  warming  effect 
on  blackened  bodies,  such  as  the  blackened  bulb  of  a  thermometer 
or  a  thermo-jimction,  held  in  this  part  of  the  spectrum.  In  the  same 
way,  beyond  the  \'iolet  end  there  is  a  long  extent  of  rays  with  high 
refrangibility  and  small  wave-length.  Though  not  perceptible  to  the 
eye,  they  reveal  their  existence  by  the  marked  influence  they  exert  on 
salts  of  silver  ;  they  are  therefore  often  spoken  of  as  the  actinic  or 
photographic  rays. 

If  the  investigation  of  the  constituent  rays  of  the  solar  spectrum 
were  carried  out  at  a  considerable  altitude  above  the  sea  and  by  means 
of  quartz  prisms  and  lenses,  the  extent  of  the  in\Tsible  spectrum 
would  be  found  to  be  largely  increased,  since  the  ultra-red  and  ultra- 
violet rays  are  absorbed  by  the  constituents,  especially  the  aqueous 
vapour,  of  the  atmosphere.  Why  can  we  not  see  these  rays  as  well  as 
those  in  the  middle  of  the  spectrum  ?  Is  it  that  they  are  absorbed  by 
the  media  of  the  eye,  through  which  the  ray  of  light  has  to  travel 
before  it  reaches  the  retina,  or  is  their  invisibility  due  to  an  actual 
insensibility  of  the  retina  to  rays  of  high  and  low  wave-lengths  ? 
On  testing  the  absorption  of  these  rays  by  the  transparent  media 
of  the  eye,  we  find  that  the  absorption  of  the  ultra-red  rays  is  but 
sliizht  and  that  a  considerable  proportion  of  these  rays  must  be  always 
arriving  at  the  retina,  so  that  their  invisibility  must  be  determined 
by  the  fact  that  they  are  unable  to  excite  the  special  sensory  elements 
of  the  retina.  On  the  other  hand,  the  absorption  of  the  ultra-violet 
rays  by  the  eye  media  is  practicallv  complete,  althouju'h  these  rays  on 
arriving  at  the  retina  have  the  power  of  evokiuir  sensation.     Thus  it 


636  PHYSIOLOGY 

has  been  observed  that  after  extraction  of  the  lens  for  cataract  the 
visibility  of  the  spectrum,  which  in  the  normal  eye  only  extends  to 
the  line  H  with  a  wave  length  of  397,  is  increased  on  the  violet  side  so 
that  the  spectrum  may  be  seen  as  far  as  a  point  corresponding  to  a 
wave  length  of  313.  It  is  evident  from  this  that  in  the  absorption 
of  the  ultra-violet  rays  by  the  eye  the  lens  takes  a  preponderating  part. 

LUMINOSITY  OF  DIFFERENT  PARTS  OF  THE  SPECTRUM 
The  physiological  nature  of  our  conception  of  light  is  shown  by 
the  fact  that  the  sj)ectrimi  dii?ers  in  its  luminosity,  i.e.  in  its  total 
stimulating  effect  on  the  retina  in  its  different  parts,  and  that  the 
relative  luminosities  of  different  parts  of  the  spectrum  bear  no  rela- 
tion to  the  amount  of  radiant  energy  represented  by  each  kind  of  wave 
length.  The  greatest  energy  is  attained  by  the  ultra-red  rays  and 
there  is  a  gradual  diminution  from  here  to  the  violet  end  of  the  spectrum. 
The  yellow  part  of  the  spectrum,  however,  appears  much  brighter 
than  any  other  part.  The  relative  luminosity  of  different  parts  is 
shown  in  the  following  Table  by  Vierordt  : 


Part  of  spectrum 

Luminosity 

Red  '  B  ' 22 

Orange  '  C ' 

128 

Reddish  yellow  '  D  ' 

780 

YeUow  '  D  '  to  '  E  ' 

1000 

Green  '  E  ' 

370 

Bluish  green  '  F  ' 

128 

Blue  '  G  ' . 

8 

Violet  '  H  ' 

1 

The  limited  excitability  of  the  retina  and  its  special  sensitivity 
to  rays  in  the  middle  of  the  spectrum  present  considerable  advantages 
for  the  normal  functioning  of  the  optical  apparatus.  No  provision 
is  made  for  securing  achromatism.  The  dispersion  of  the  ultra-red 
and  ultra-violet  rays  is  so  great  in  passing  through  the  refracting 
surfaces  of  the  eyeball  that,  if  they  all  arrived  at  the  retina,  and  this 
organ  were  sensitive  to  both  kinds  of  rays,  it  would  be  impossible  to 
obtain  any  clear  image  of  external  objects.  The  image  formed  by  the 
ultra-red  rays  would  be  far  behind  the  retina  when  the  ultra-violet 
rays  were  focused  on  the  retina  and  vice  versa.  As  it  is,  the  retina 
is  unstimulated  by  the  two  ends  of  the  spectrum,  and  its  stimulation 
by  the  red  as  well  as  by  the  blue  rays  is  only  minimal,  so  that,  for  the 
excitation  of  a  mosaic  of  spots  on  the  retina  in  spatial  extension  and 
arrangement  corresponding  to  that  of  the  objects  from  which  the  hght 
reaches  the  retina,  practically  only  the  middle  pai-t  of  the  spectrum  is 
of  importance,  and  the  distance  of  the  image  formed  by  the  reddish- 
yellow  rays  from  that  formed  by  the  green  rays  will  not  be  great 
enough  to  cause  any  appreciable  distortion  of  the  exciting  image. 


VISUAL  SENSATIONS  637 

THE  RELATION  OF  THE  INTENSITY  OF  SENSATION  TO 
THE  STRENGTH  OF  STIMULUS 
Weber's  law,  viz.  that  tlie  increase  of  stimulus  necessary  to 
give  an  increase  of  sensation  always  bears  the  same  ratio  to  the  whole 
stimulus,  holds  good  for  visual  sensations.  This  ratio  in  the  case  of 
white  light  is  about  v^o-  We  can  thus  distinguish  between  two 
lights  of  20  and  201  candle-power,  both  of  them  at  the  same  distance 
from  the  eye,  or  between  two  of  99  and  100  candle-power.  If  the 
illumination  be  excessive  the  law  no  longer  holds  good,  and  we  should 
be  unable  to  tell  the  difference  between  two  lights  of  the  latter  power 
if  held  close  to  the  eye,  or  between  two  arc  lamps  at  a  considerable 
distance,  even  though  one  might  be  much  stronger  than  the  other. 
According  to  some  authors  our  power  of  distinguishing  differences  in 
luminosity  varies  with  difierent  colours. 

TIME  RELATIONS  OF  THE  EXCITATORY  PROCESS 
When  a  stimulus  of  short  duration,  such  as  an  induction  shock, 
is  applied  to  a  muscle,  the  response  of  the  latter  bears  no  likeness 
in  its  intensity  and  its  time-relations  to  the  exciting  stimulus.  The 
muscle  after  a  short  latent  period  begins  to  contract  when  the  stimulus 
has  already  ceased  to  act.  It  contracts  rapidly  at  first,  then  more 
slowly,  and  then  relaxes.  In  the  same  way  the  sensation  evoked  by 
a  momentary  light  stimulus  takes  a  certain  time  to  attain  its  maximum 
and  then  dies  away  slowly,  persisting,  that  is  to  say,  during  a  certain 
interval  after  the  stimulus  has  been  entirely  withdrawn.  This  per- 
sistence of  the  visual  sensation  is  experienced  whenever  we  look  at  a 
brilUant  source  of  light,  such  as  a  candle  or  lamp,  and  then  either 
shut  the  eyes  or  direct  the  gaze  on  to  a  blackened  surface.  We  then 
see  on  the  dark  background  a  bright  image  of  the  candle  or  lamp, 
which  gradually  fades.  This  phenomenon  is  often  spoken  of  as  a 
'  positive  after-image.'  If  the  object  has  been  very  bright  the  image 
in  fading  becomes  coloured.  It  first  appears  greenish  blue,  which 
changes  later  to  violet,  rose  colour,  and  finally  orange  or  green. 

The  slow  rise  and  fall  of  the  sensation  evoked  by  a  momentary 
stimulus,  or  by  a  change  in  the  intensity  of  light  falling  on  the  retina,  are 
responsible  for  the  blurred  outline  of  any  object  that  is  regarded  while 
in  rapid  motion.  If  a  disc  with  alternate  sectors  of  black  and  white, 
such  as  is  shown  in  Fig.  293,  be  caused  to  rotate  slowly,  it  is  easy  to  dis- 
tinguish both  black  and  white  sectors.  As  the  speed  of  rotation 
increases  the  margins  of  the  sectors  become  blurred,  and  the  fact  that 
both  margins  of  each  white  sector  are  blurred  shows  that  the  sensations 
produced  both  by  the  application  and  by  the  shutting  oft'  of  the  stimu- 
lus, and  due  to  the  white  light  reflected  from  the  surface,  are  gradual 


638  PHYSIOLOGY 

and  not  instantaneous.  With  further  increase  in  rate  the  whole  disc 
takes  a  grey  colour,  which,  however,  oscillates  or  '  flickers,'  and  with 
a  still  further  increase  the  '  flicker  '  disappears  and  the  disc  has  a 
uniform  grey  appearance.  The  phenomenon  is  analogous  to  the 
phenomenon  observed  in  muscle  as  the  result  of  intermittent  excita- 
tion. Each  single  shock  gives  rise  to  a  contraction  which  is  more 
prolonged  than  the  shock  itself.  When  the  shocks  are  repeated 
we  obtain,  according  to  their  frequency,  a  series  of  single  contrac- 
tions, a  partial  fusion  of  contractions,  so  that  an  imperfect  tetanus  is 
produced  ("'  flicker  '),  or  finally — with  a  certain  rate  of  interruption  of 
the  stimulus — complete  fusion  of  contraction,  t.e.  complete  tetanus. 
We  see  therefore  that' when  a  portion  of  the  retina  is  excited 

for  a  certain  period  by  rays  of  a 
given  intensity  during  a  period  A, 
and  is  then  unilluminated  during 
a  period  B,  if  A  +  B  is  sufficiently 
small,  e.g.  in  the  case  of  the  disc  if 
the  rotation  is  sufficiently  rapid,  the 
sensation  evoked  is  a  continuous 
one  and  is  equal  to  that  which  would 
be  produced  by  a  continuous  stimu- 

A 

lation   which   is    equal  to     . 

^  A  +  B 

This  fact  is  spoken  of  as  Talbot's 

~^  ."03  l^w.      It   enables  us  to   produce  a 

tgTey    of   any  desired   intensity  by 

varying  the  relative  sizes  of  black  and  white  sectors  on  a  rotating 

disc.     For  complete  fusion  to  take  place  the  period  A  +  B   need 

not  be  less  than  -04  sec.  if  we  are  using  light  of  moderate  strength. 

With  low  intensity  of  illumination    this   value   rises,   i.e.   complete 

fusion  is  obtained  with  a  lower  rate  of  rotation  of  disc  than  when 

we  are  using  bright  illumination.     The  value  also  varies  according  to 

the  colour  of  the  light.     Different  colours  require  different  times  for 

their  action  on  the  retina  in  order  to  produce  the  maximum  sensation. 

If  a  spectrum  be  exposed  to  the  eye  for  a  very  short  period  of  time  it 

appears  colourless  and  shortened  at  the  red  end.     If  the  period  of 

exposure  be  increased  the  red  and  blue  ends  are  seen,  but  no  other 

colour  is  perceptible".     The  sensations  due  to  the  incidence  of  red  rays 

attain  their  maximum  in  the  shortest  time,  then  come  blue  rays,  while 

the  gTeen   take  the  longest  time  to  attain   their  maximum.      This 

difference  between  the  time-relations  and  the  sensations  evoked  by 

the   various   rays  accounts  for  the  fact   that   on  rotating  a  disc  of 

alternate  white  and  black  sectors  at  a  certain  rate  the  sectors  appear 

blurred  and  bounded  by  coloured  fringes. 


VISUAL  SENSATIONS  639 

FATIGUE 
If  a  constant  stinuilus  be  piolonucd.  the  intensity  of  the  resulting 
sensation  rapidly  diminishes,  i.e.  the  apparatus  concerned  in  the  pro- 
duction of  the  sensation  shows  signs  of  fatigue.  This  diminution  in 
the  intensity  of  sensation  may  be  observed  so  early  as  one-iifth  of  a 
second  after  the  beginning  of  the  stimulus.  Connected  with  this 
fatigue  of  the  retina  is  the  phenomenon  known  as  the  '  negative  after- 
image.' If  we  look  at  a  bright  spot  or  source  of  light  for  some  seconds 
and  then  turn  our  gaze  to  a  uniformly  illuminated  white  surface,  we 
see  in  the  middle  of  the  white  surface,  i.e.  at  the  point  of  fixation,  a 
dark  image  of  the  bright  object  which  we  had  previously  looked  at. 
The  stimulus  applied  to  all  parts  of  the  retina  in  this  case  is  uniform. 
Certain  elements,  however,  i.e.  those  which  had  been  previously 
stimulated  by  the  bright  object,  are  fatigued.  Their  response  is 
therefore  less  than  that  of  the  surrounding  untired  retinal  elements, 
and  the  resulting  sensation  is  a  dark  image,  which  is  referred  to  that 
part  of  the  white  surface  from  which  proceeds  the  light  falling  on  the 
fatigued  elements  of  the  retina. 

ADAPTATION 

It  is  common  experience  that  our  eyes  have  the  power  of  adapting 
their  sensitiveness  according  to  the  degree  of  illumination.  When 
we  pass  from  daylight  into  a  dark  room,  such  as  the  developing  chamber 
of  the  photographer,  it  is  at  first  impossible  to  distinguish  any  objects 
even  by  the  dim  red  light  coming  from  the  photographer's  lamp  or  the 
window.  After  a  short  time,  however,  we  begin  to  distinguish  objects 
more  clearly.  Any  slight  defects  in  the  dark  chamber  begin  to  make 
themselves  apparent,  such  as  entry  of  light  under  the  door  and  through 
cracks  or  nail-holes  in  the  ceiling  or  walls.  By  direct  measurement 
it  can  be  shown  that  within  ten  minutes  after  passing  from  daylight 
into  complete  darkness  the  sensitiveness  of  the  retina  increases  twenty- 
five-fold,  and  after  two  hours'  exposure  to  complete  darkness  thirty-five- 
fold. On  the  other  hand,  on  coming  out  of  the  dark  room  we  are  at 
first  dazzled  by  the  flood  of  light  with  which  w^e  appear  to  be  sur- 
rounded ;  the  pupils  constrict  to  their  utmost,  and  accurate  vision 
is  impossible  on  account  of  the  excess  of  light  which  seems  to  pour 
into  our  eyes.  Very  shortly  this  condition  passes  off,  and  within  five 
minutes  vision  is  once  more  normal,  and  the  ordinary  size  6f  the  pupils 
re-established. 

The  process  of  adaptation  affects  not  only  the  quantitative  rela- 
tion between  the  intensity  of  the  stimulus  and  the  resulting  sensation, 
but  determines  also  a  qualitative  alteration  in  the  reaction  of  the  retina 
to  light.     This  is    especially   marked    in  the   case  of  colours.      On 


640  PHYSIOLOGY 

going  into  a  flower-garden  on  a  summer  morning,  when  dawn 
is  just  beginning,  although  all  objects  in  the  garden  can  be  clearly  dis- 
tinguished, there  is  a  striking  difference  in  its  colour-tone  as  compared 
with  that  which  it  presents  in  daylight.  The  scarlet  geraniums  have 
disappeared.  On  close  examination  this  disappearance  is  found  to 
be  due  to  the  fact  that  the  flowers  are  dark,  i.e.  the  light  from  them 
does  not  stimulate  the  retina  at  all.  The  other  coloured  flowers  can 
be  distinguished,  but  only  in  shades  of  grey.  With  a  very  little  increase 
in  illumination  the  blue  flowers  come  into  evidence  and  the  prevailing 
tone  of  the  garden  is  cold,  made  up  as  it  is  of  greens,  blues,  and  gi'eys. 
With  increasing  illumination  the  reds  finally  make  their  appearance. 
After  long  exposure  to  the  darkness  of  night  the  eyes  have  become 
dark-adapted.  The  same  behaviour  of  the  dark-adapted  eye  may 
be  demonstrated  in  the  laboratory.  If  a  person  who  has  been  in  a 
dark  room  for  half  an  hour  observes  a  spectrum  of  low  intensity  the 
w'hole  spectrum  appears  colourless,  its  red  end  being  cut  off.  The 
distribution  of  limainosity  over  the  spectrum  is  also  altered.  Whereas 
the  spectrum  to  the  normal  light-adapted  eye  appears  brightest  in  the 
yellow  between  the  Hnes  D  and  E,  the  spectrum  of  low  intensity  to  the 
dark-adapted  eye  has  its  point  of  greatest  luminosity  in  the  green. 

This  striking  difference  between  the  light-adapted  and  the  dark- 
adapted  eye  does  not  apply  to  small  objects  the  image  of  which, 
when  the  vision  is  directed  towards  them,  will  fall  entirely  on  the 
fovea  centrahs  of  the  retina.  In  the  dark-adapted  eye  the 
sensitiveness  of  the  central  spot  of  the  retina  is  not  nearly  so 
great  as  that  of  the  more  peripheral  portion.  On  a  dark  night  we 
are  often  able  to  distinguish  a  star  which,  however,  disappears  as 
soon  as  we  turn  our  eyes  so  as  to  bring  its  image  on  the  central 
spot  of  the  two  retinae.  Moreover  the  qualitative  change  in  relation 
to  the  colours  observed  in  the  dark- adapted  eye  does  not  apply 
to  the  fovea  centrahs.  In  a  dark  room  a  small  spot  of  light,  whatever 
its  colour,  when  the  visual  axes  are  directed  on  it,  is  seen  in  its  true 
colour  as  soon  as  its  intensity  is  sufficient  for  it  to  be  seen  at  all.  Before 
this  takes  place  it  may  be  seen  by  the  peripheral  parts  of  the  retina,  but 
as  a  colourless  spot  of  light  which  disappears  as  soon  as  the  gaze  is 
directed  on  it.  This  marked  difference  between  the  behaviour  of  the 
fovea  centralis  and  the  more  peripheral  parts  of  the  retina  in  the  dark- 
adapted  eye  has  been  attributed  to  the  difference  we  have  already 
studied  in  the  anatomical  structure  of  these  parts.  The  only  per- 
cipient elements  found  in  the  fovea  centrahs  are  the  cones.  In  the 
adjacent  portion  of  the  retina  we  find  also  the  rods  which  increase  in 
relative  number  as  we  pass  from  the  central  spot  towards  the  periphery. 
Schultz  long  ago  pointed  out  that  in  the  retina)  of  many  night  animals, 
such  as  the  owl,  the  mouscj  ^he  c^-t,  the  rods  are  the  predominating 


VISUAL  SENSATIONS  041 

element,  the  cones  being  absent  or  very  few  in  number.  Von  Kries 
has  suggested  that  in  all  probability  the  retina  is  endowed  with  two 
kinds  of  vision. 

(a)  Vision  by  means  of  rods,  which  are  colour-blind,  so  that  on 
stimulation  by  any  rays  of  the  retina  a  sensation  of  white  or  grey 
is  produced.  The  rods  are  chiefly  excited  by  the  more  refrangible 
rays  of  the  spectrum,  being  totally  unaffected  by  the  red  rays.  They 
show  great  power  of  adaptation.  This  form  of  rod  vision  may  be 
connected  with  the  visual  purple.  In  the  dark-adapted  eye  this  pig- 
ment is  found  pervading  the  whole  of  the  outer  limbs  of  the  rods ;  it 
rapidly  fades  on  exposure  of  the  eye  to  light,  so  that  it  must  be  absent 
in  the  light-adapted  eye.  On  examining  its  absorption  spectrum  we 
find  that  its  absorptive  power  is  greatest  for  the  rays  in  the  green  part 
of  the  spectrum,  and  that  it  allows  the  red  rays  to  pass  almost  without 
absorption,  i.e.  it  absorbs  just  those  rays  which  experiment  shows  us 
have  the  greatest  effect  in  producing  a  sensation  of  light  in  the  dark- 
adapted  eye. 

(6)  The  cones,  on  this  view,  would  represent  a  more  highly  dif- 
ferentiated apparatus  of  vision.  They  alone  are  present  in  that  part 
of  the  retina  which  we  use  exclusively  for  distinguishing  the  finer  details 
of  surrounding  objects  ;  they  are  sensitive  to  all  colours,  and  when 
stimulated  by  all  the  rays  of  the  spectrum  simultaneously  give  rise  to  a 
sensation  of  white  light.  Their  sensitiveness  to  illumination  is,  however, 
inferior  to  that  of  the  rod  apparatus.  According  to  this  theory,  there- 
fore, whereas  in  a  dim  light  we  determine  the  position  of  surrounding 
objects  and  differences  in  their  luminosity  by  means  of  the  rods,  the 
greater  part  of  our  visual  impressions,  including  all  that  we  obtain 
by  daylight  and  our  knowledge  of  the  finer  visual  qualities  of  things, 
are  brought  to  us  by  the  intermediation  of  the  cones. 

COLOUR  VISION 
If  a  ray  of  white  light  be  passed  through  a  prism  it  is  widened  out 
into  a  bright  coloured  band  or  spectruUi,  the  red  rays,  which  are 
least  refrangible,  being  at  one  end,  and  the  blue  rays  at  the  other. 
It  is  usual  to  divide  the  colours  of  the  spectrum  into  seven — red, 
orange,  green,  yellow,  blue,  indigo,  violet ;  but  the  division  is  an 
arbitrary  one,  and  the  colours  shade  into  one  another  so  gradually 
that  no  two  observers  would  agree  exactly  on  the  limits  between 
them.  The  difference  of  wave-length  necessary  to  give  a  distinct 
difference  in  colour  varies  according  to  the  part  of  the  spectrum 
which  is  under  observation.  In  the  middle  of  the  spectrum 
it  is  between  0-7  /mfx  and  20  /u/ul.  At  the  red  end  a  difference  of. 
4"7  /iifi  is  required  to  evoke  a  new  quality  of  sensation,  and  at  the 
extreme  end,  both  red  and  violet,  there  is  a  section  of  the  spectrum 

41 


642  PHYSIOLOGY 

over  which  no  variation  in  colour  can  be  perceived.  By  passing 
the  rays  forming  a  spectrum  through  a  similar  prism  placed  in  the 
reverse  direction,  all  these  rays  can  be  recomposed  to  form  white 
light.  The  sensation  of  white  light  is  therefore  due  to  the  simul- 
taneous incidence  on  the  retina  of  all  the  rays  of  the  spectrum.  That 
we  have  no  suspicion  of  the  existence  of  these  rays  when  we  experi- 
ence a  sensation  of  white  shows  that  our  eye  does  not  possess  any 
resolving  or  analysing  apparatus  such  as  exists  in  the  internal  ear 
for  the  compound  wave  of  sound. 

Any  part  of  the  spectrum,  or  any  coloured  object,  may  be  char- 
acterised in  three  different  ways  : 

(1)  LUMINOSITY.  The  luminosity  of  different  parts  of  the 
spectrum  varies,  being  greatest  in  the  yellow  for  the  light-adapted 
eye.  We  could,  however,  match  the  luminosity  of  the  red  of  one 
spectrum  with  that  of  the  yellow  of  a  second  spectrum  by  increasing 
the  intensity  of  the  beam  of  light  used  to  produce  the  first  spectrum. 

(2)  SHADE  OR  COLOUR.  It  has  been  reckoned  by  Konig  that 
in  the  spectrum  we  can  distinguish  165  different  shades  of  colour. 
Edridge-Green  has  shown  that  when  a  normal  observer  screens  off 
the  rest  of  the  spectrum  until  the  part  left  appears  monochromatic, 
and  repeats  this  operation  through  the  whole  length  of  the  spectrum, 
he  will  mark  off  not  more  than  eighteen  to  twenty-seven  '  mono- 
chromatic patches.'  There  are  certain  colours  which  can  be  appre- 
ciated by  the  eye  which  are  not  present  in  the  spectrum,  such  as  the 
varying  shades  of  ])urple. 

(3)  SATURATION.  When  we  look  at  a  coloured  surf  ace,  e.gr.  red,  our 
eye  is  stimulated  partly  by  the  white  light  which  is  reflected  in  toto  from 
the  surface,  partly  by  the  red  rays  which  are  specifically  reflected  and 
give  the  colour  of  the  object.  According  as  these  red  rays  are  free 
from  mixture  with  white  rays,  so  their  saturation  is  said  to  increase. 
The  degree  of  saturation  of  any  colour  can  be  determined  by  regarding 
it  through  a  spectroscope.  A  completely  saturated  red  would  give 
only  rays  at  the  red  end  of  the  spectrum.  We  can,  however, 
speak  not  only  of  a  psychical  but  of  a  physiological  saturation. 
According  to  the  condition  of  the  retina  and  nature  of  the  stimuli  to 
which  it  has  been  previously  exposed,  so  does  the  saturation  of  any 
given  colour  vary. 

It  might  at  first  be  thought  that  the  retina  could  respond  with  a 
simple  sensation  to  a  stimulus  by  any  part  of  the  spectrum,  a  low 
number  of  ether  vibrations  per  second  producing  a  sensation  of  red, 
a  number  rather  higher  a  sensation  of  orange  ;  so  that  there  might  be 
as  many  simple  colour-sensations  as  we  can  appreciate  different 
shades  in  the  spectrum.  But  a  simple  analysis  of  our  own  sensations 
seems  to  show  that  some  of  the  spectral  colours,  although  simple  in 


VISUAL  SENSATIONS  043 

so  far  as  the  stimuli  are  concerned,  are  compound  so  far  as  the  sensa- 
tion is  concerned.  Thus  most  people  would  say  at  once  that  orange 
is  a  mixture  of  red  and  yellow,  and,  as  a  matter  of  fact,  we  find  that 
on  mixing  rays  from  the  red  with  others  from  the  yellow  part  of  the 
spectrum  we  do  obtain  a  sensation  of  orange.  The  stimulus  obtained 
by  mixing  the  red  and  yellow  rays  is  not  the  same  as  a  stimulus 
caused  by  rays  from  the  orange  part  of  the  spectrum.  In  the  former 
case  compound  waves  made  up  of  the  two  wave-lengths,  656  h/j.  and 
564  /u^t,  are  falling  on  the  retina,  in  the  latter  case  a  simple  wave 
with  a  length  of  608  /x/z,  and  yet  the  sensations  produced  are  identical. 
Experience  shows  that  there  are  relations  between  the  physiological 
effects  produced  by  different  parts  of  the  spectrum  which  have  no 
physical  analogue  in  the  stimuli  themselves.  Such,  for  instance,  are 
the  phenomena  known  as  the  coloured  after-image.  We  have  seen 
that,  as  the  result  of  fatigue,  stimulation  of  any  part  of  the  retina 
by  a  bright  object  produces,  when  stimulation  is  removed,  a  dark 
after-image,  which  has  its  seat  in  the  previously  stimulated  portion 
of  the  retina.  If  we  look  steadfastly  for  a  minute  in  a  bright  light 
at  a  red  disc  on  a  white  ground  and  then  look  away  at  a  uniform 
white  surface,  we  see  an  after-image  of  the  disc  on  the  surface.  This 
after-image  is,  however,  green,  and  the  white  background  takes  on 
a  reddish  tinge.  If  the  disc  in  the  first  instance  has  been  a  greenish 
blue  the  after-image  is  red,  and  to  every  colour  in  the  spectrum  we 
find  there  corresponds  another  which  represents  the  after-image 
evoked  by  stimulation  with  the  first  colour.  If  the  first  disc  has 
been  green  the  after-image  will  be  purple,  and  vice  versa.  We 
can  therefore  arrange  the  spectrum  into  a  series  of  pairs  of  colours 
which  are  known  as  complementary.  The  following  is  a  list  of 
such  pairs,  with  wave-lengths  of  the  rays  involved,  as  determined 
by  Helmholtz  : 

Colours  Wave-lengths 

Red— -greenisli  h\\\c  ....     656 — 492 


Orange — blue  . 
Bright  yellow-  bliir . 
Yellow — indigo 
Greenish  j-ellow — viulel 


608—490 
574—482 
567—465 
564—433 


If  the  retina  be  stimulated  by  any  of  these  pairs  of  colours  simul- 
taneously the  effect  is  not  that  of  colour,  but  of  white.  White  light, 
or  the  sensation  of  white,  can  thus  be  due  either  to  simultaneous 
stimulation  of  the  retina  by  all  tlie  rays  of  the  spectrum,  or  to  stimu- 
lation of  the  retina  by  pairs  of  colours  which  are  known  as  comple- 
mentary. If  these  pairs  be  taken  rather  nearer  in  the  spectrum 
a  colour  is  obtained  representing  a  jiart  of  the  spectrum  situated 
between  the  two  constituents  of  the  pair.     If  the  rays  are  further 


644  PHYSIOLOGY 

away  than  would  correspond  to  the  complementary  colours  we  obtain 
again  a  coloured  sensation,  which,  however,  is  unsaturated,  being 
mixed  with  a  certain  amount  of  white  light.  By  taking  three  colours, 
such  as  red,  green,  and  violet,  or  four  colours,  such  as  red,  yellow, 
green,  and  violet,  it  is  possible  by  mixing  them  in  various  proportions 
to  form  either  white  light  or  any  colour  of  the  spectrum,  besides 
the  various  jmrples  which  do  not  occur  in  the  spectrum. 

These  experiments  of  mixing  colours  can  be  carried  out  in  various  ways  : 
In  every  case  we  aim  at  stimulating  the  retina  simultaneously  with  rays 
of  different  wave-lengths,  or  successively  at  such  short  intervals  of  time  that 
there  is  complete  fusion  of  the  sensations  resulting  from  the  individual  excita- 
tions. In  order  to  determine  fine  differences  in  shade  a  coloiu'ed  surface  is 
always  provided  with  which  a  coloiu',  produced  by  the  fusion  of  the  different 
rays  under  experiment,  may  be  compared  : 

( 1 )  The  most  exact  method  of  mixing  colom's  is  to  employ  a  couple  of  spectra 
and  by  means  of  prisms  to  bring  different  parts  of  the  spectra  on  one  and  the 
same  white  surface  on  which  the  result  of  the  mixtiire  can  be  compared  with 
sample  colour's. 

(2)  In  Maxwell's  '  colour  top'  discs  with  a  radial  slit  are  placed  one  over 
the  other  on  a  disc  which  can  be  made  to  revolve  with  considerable  rapidity. 
By  means  of  the  slit  two  or  three  discs  of  different  colours  can  be  slid  one  into 
the  other,  so  that  the  disc  is  composed  of  sectors  of  variable  extent  of  the  two 
or  three  colours  which  we  wish  to  mix.  These  discs  are  generally  mounted 
on  a  background  of  a  larger  disc,  which  can  be  used  as  a  sample  colour  to  com- 
pare with  the  result  of  the  mixtm-e  of  the  colom-s  in  the  centre.  If  we  are 
determining  the  relative  amount  of  different  colours  necessary  to  produce  white, 
the  outside  disc  w'ould  be  partly  white  and  partly  black,  so  that  on  rotation 
the  effect  of  grey  is  produced,  i.e.  a  weak  white.  Thus  in  one  experiment  the 
small  discs  in  the  centre  were  red,  green,  and  blue.  It  was  found  that  when 
the  sectors  were  chosen  in  the  following  proportion  :  165  red,  122  green,  and 
73  blue,  a  grey  coloru"  was  produced  equal  to  the  grey  obtained  in  the  outer 
disc  by  mixing  100  white  with  260  black. 

These  methods  and  all  others,  in  which  coloured  surfaces  are  used 
suffer  from  the  defect  that  no  pigments  give  perfectly  pure  colour- 
sensations.  On  looking  at  a  red  painted  surface,  for  instance,  in 
a  bright  light  with  a  spectroscope,  it  will  be  found  that  the  spectrum 
contains  yellow  and  green  rays  as  well  as  red.  On  this  account  no 
information  as  to  the  effect  of  mixing  colour-sensations  can  be 
obtained  by  mixing  the  pigments  themselves.  Thus  a  familiar  way 
of  producing  a  green  pigment  is  to  mix  a  blue  and  a  yellow  pigment. 
A  mixture  of  blue  and  yellow  rays  will  give  a  sensation  of  white. 
The  fact  that  blue  and  yellow  pigment  mixed  together  give  a  green 
pigment  is  due  to  the  fact  that  the  blue  pigment  cuts  ofE  the  red 
and  yellow  rays,  and  reflects,  or  allows  to  pass,  the  blue  and  green 
rays,  while  the  yellow  pigment  retains  the  blue  and  violet  rays,  but 
reflects  the  red,  yellow,  and  green  rays.  When  we  mix  the  two 
we  get,  not  an  addition,  but  a  subtraction  ;  the  blue  pigment  absorbs 
the  red  rays  which  the  yellow  pigment  allows  to  pass,  and  the  yellow 


VISUAL  SENSATIONS 


645 


pigment  absorbs  the  blue  rays  which  the  bhio  allows  to  pass.  The 
only  rays  left  over  are  the  green,  and  the  mixture  of  pigment  has  a 
green  colour. 

THEORIES  OF  COLOUR  VISION 

These  facts  show  that  in  all  ])rol)al)ility  the  primitive  colour- 
sensations  are  few  in  number,  and  that  the  various  sensations  excited 
by  the  different  parts  of  the  spectrum  are  not  simple,  but  are  com- 
pounded of  mixtures  of  these  primary  sensations.  The  two  theories 
which  have  obtained  most  vogue,  and  which  enable  us  to  account  for 
a  certain  number  of  the  phenomena  associated  with  colour-vision,  are 
those  known  as  the  Young-Helmholtz  theory  and  the  Hering  theory. 

(a)  THE  YOUNG-HELMHOLTZ  THEORY.  This  theory,  which 
was   first    put   forward    by    Young   and   elaborated    by   Helmlioltz, 


Fiu.  294. 


^  ^  Gr.  JBL  V 

Curves  showing  sensitiveness  of  the  three  varieties  of  nerve  fibres 
to  different  parts  of  the  spectrum. 
1,  red  fibres  ;  2,  green  fibres  ;   3,  violet  fibres. 


assumes  that  there  are  three  primary  colour-sensations — red,  green, 
and  violet- — which  are  represented  by  three  separate  sets  of  elements 
in  the  retina,  or  in  each  cone,  or  by  separate  substances,  each  of 
which  is  affected  by  one  of  these  colours. 

Thus  the  rays  with  a  longer  wave-length  excite  chiefly  the  red 
fibres  or  elements  ;  those  of  medium  wave-length  the  green  percipient 
element  ;  those  of  short  wave-length  the  violet  percipient  element 
of  the  retina.  The  excitability  of  these  three  elements  by  the  rays 
of  different  parts  of  the  spectrum  are  represented  in  the  figure 
(Fig.  294).  At  the  extreme  red  and  violet  end  of  the  spectrum 
alterations  of  the  wave-length  cause  no  alteration  in  colour,  showing 
that  these  rays  only  excite  either  the  red  or  the  violet  fibres.  All 
other  parts  of  the  spectrum  excite  the  three  sets  of  fibres  simultaneously 
but  to  varying  degrees.  Thus  the  greater  part  of  the  red,  e.g.  about 
'  C,'  excites  the  red  percipient  element  strongly,  the  other  two 
only  weakly  ;  the  result  is  a  sensation  of  red.  The  yellow  rays  at 
'  D  '  excite  almost  equally  the  red  and  the  green  percipient  elements, 
but  the  violet  only  slightly.    Yellow  is  therefore  a  mixed  sensation. 


646  PHYSIOLOGY 

The  green  rays  excite  the  green  percipient  element  strongly,  the 
other  two  slightly,  with  green  sensation  as  a  result.  Blue  rays  excite 
green  and  violet  percipient  elements  to  a  moderate  extent,  and  the 
red  rays  to  a  somewhat  less  extent ;  blue  is  therefore  a  mixed  sensa- 
tion composed  chiefly  of  green  and  violet.  Simultaneous  excitation 
of  all  three  elements  evokes  a  sensation  of  white  or  grey,  according 
to  the  intensity. 

The  cases  of  defective  colour-vision  which  occur — the  so-called 
colour-blindness — are  regarded  under  this  theory  as  due  to  the 
absence  of  one  or  other  of  the  elements  which  determine  the  primary 
colour-sensations.  The  normal  eye  is  spoken  of  as  trichromatic 
since  it  has  three  primary  colour-sensations.  Two  kinds  of  dichromatic 
eyes  are  described — those  in  which  the  red  sensation  is  lacking,  and 
those  in  which  the  green  sensation  is  lacking.  In  either  of  these 
cases  the  subject  confuses  red  and  green.  The  ripe  cherry  on  a  tree 
they  may  distinguish  from  the  leaves,  not  by  their  colour,  but  by 
form  or  difference  in  their  luminosity.  It  is  only  when  they  are 
tested  by  means  of  the  spectrum  that  we  find  that  whereas  in  the 
first  case  (red  blindness)  there  is  insensibility  to  the  red  end  of  the 
spectrum,  in  the  second  case  the  red  end  of  the  spectrum  is  seen  as 
well  as  by  the  normal  person,  so  that  the  defect  must  be  located 
towards  the  middle  of  the  spectrum.  Theoretically,  of  course,  violet 
blindness  ought  also  to  exist,  but  cases  of  this  nature  are  so  rare 
that  their  very  existence  is  doubted.  Cases  have  also  been  recorded 
with  total  colour-blindness  (so-called  monochromatic  vision).  Such 
cases  have  been  supposed  to  be  endowed  only  with  vision  similar 
to  that  found  in  the  dark-adapted  eye,  i.e.  with  sensations  only  of 
white  and  black  rather  than  vision  determined  only  by  the  existence 
of  the  violet  perceiving  constituent  of  the  cones.  Indeed  the 
phenomena  we  have  studied  under  the  heading  of  dark  adaptation 
would  tend  to  show  that,  if  we  accept  the  Young-Helmholtz  theory, 
we  should  add  to  the  primary  visual  sensations  those  of  light  and 
dark,  which  have  their  seat  in  the  rods. 

(6)  THE  HERING  THEORY.  According  to  Hering  there  are 
four,  and  not  three,  primary  colour-sensations,  viz.  red,  yellow,  green, 
and  blue.  In  this  theory  the  sensations  of  white  and  black  are 
also  regarded  as  primary  visual  sensations.  These  sensations  are  placed 
in  three  groups — red  and  green,  yellow  and  blue,  white  and  black. 
For  each  pair  of  sensations  he  considers  that  there  is  a  special 
substance  in  the  retina,  dissimilation  or  catabolism  of  which  gives 
rise  to  one  colour-sensation  ;  anabolism  or  assimilation  to  the  other. 
Thus  if  white  light  falls  on  the  retina,  it  causes  a  breaking  down  or 
catabolism  of  the  white-black  substance.  This  breaking  down  excites 
certain  fibres  of  the  optic  nerve,  and  produces  in  consciousness  a 


VISUAL  SENSATIONS  047 

sensation  of  white.  If  the  light  be  now  removed,  this  breaking  down 
gives  place  to  anabolism  or  building  up  of  the  white-black  substance, 
which  excites  the  same  nerve  fibrils  in  a  different  way,  giving  rise  to 
a  sensation  of  black.  The  white-black  substance  is  affected  not 
only  by  white  light  but  also  by  the  colours  red,  green,  yellow,  blue, 
and  their  mixtures.  The  other  two  visual  substances  are  affected 
only  by  red  and  green  or  by  yellow  and  blue  respectively.  Hence 
even  the  spectral  colours  do  not  give  rise  to  pure  sensations,  there 
being  always  some  mixture  of  a  sensation  of  white  with  the  proper 
colour-sensation. 

Most  of  the  phenomena  of  colour-vision  that  we  have  mentioned 
above  can  be  equally  well  explained  on  either  theory.  Thus  the 
fact  that  blue  and  yellow  together  give  rise  to  a  sensation  of  white 
may  be  explained  on  the  Young-Helmholtz  theory  by  saying  that 
the  stimulation  of  all  three  sets  of  fibrils  is  equal,  as  will  be  seen  by 
adding  together  the  ordinates  of  each  curve  in  Fig.  294  at  yellow 
and  at  blue. 

Adopting  Hering's  hypothesis,  we  may  say  that,  anabolism  and 
catabolism  being  equally  excited  in  the  yellow-blue  substance,  no 
change  in  it  takes  place,  and  the  sole  sensation  is  that  produced 
by  the  stimulation  of  the  white-black  substance.  The  pairs  of  colours 
that  we  have  distinguished  are  therefore,  according  to  this  theory, 
not  in  the  strict  sense  of  the  word  comflementary,  but  antagonistic. 
The  fact  that  white  light  appears  to  us  as  a  simple  sensation  and 
gives  us  no  suspicion  of  the  coloured  rays  of  which  it  may  be  com- 
posed is  in  favour  of  Hering's  theory.  Cases  of  colour-blindness 
would  be  reduced  by  Hering  to  two  classes,  viz.  those  in  which  the 
red-green  substance  is  lacking  and  those  in  which  the  yellow-blue 
substance  is  lacking.  Most  of  the  data  with  regard  to  colour-blind- 
ness have  been  worked  out  with  reference  to  the  Young-Helmhcltz 
theory,  and  have  therefore  been  interpreted  in  accordance  with  this 
hypothesis. 

It.  is  very  difficult,  however,  to  harmonise  the  facts  of  colour- 
blindness either  with  this  or  with  Hering's  hypothesis.  It  is  better 
therefore  to  abandon  hypotheses  altogether  and  to  adopt  a  purely 
empirical  classification  of  colour-vision,  as  has  been  done  by  Edridge- 
Green.  This  observer  points  out  truly  that  very  marked  colour- 
blindness may  be  present  without  any  interference  with  the  apprecia- 
tion of  the  luminosity  of  any  part  of  the  spectrum.  A  person  may 
be  able  to  see  the  spectrum  up  to  its  extreme  red  end.  and  yet  dis- 
tinguish in  the  spectrum  only  two  colours,  which  we  may  call  red 
and  violet.  We  may,  in  fact,  regard  discrimination  of  colour  differ- 
ence as  superadded  to  and  evolved  later  than  the  appreciation  of 
light.     Discrimination  may  show  various  degrees  of  deficiency  without 


648  PHYSIOLOGY 

anv  interference  with  the  appreciation  of  kiminosity.  According  to 
Edridge-Green  a  normal  individual  will  name  six  distinct  colours  in  the 
spectrum — red.  orange,  yellow,  green,  blue,  violet.  Such  an  individual, 
when  made  to  map  out  the  spectrum  in  the  manner  indicated  on 
p.  642,  will  distinguish  about  eighteen  monochromatic,  patches. 
A  few  individuals  will  place  another  colour,  which  has  been  called 
indigo,  between  the  blue  and  the  violet,  and  will  mark  out  from 
twenty-two  to  twenty-nine  monochromatic  patches. 

'  Colour-bhndness  '  may  be  brought  about  by  one  of  two  con- 
ditions :  (o)  a  shortening  of  the  red  or  violet  end  of  the  spectrum ; 
(b)  absence  of  power  to  discriminate  between  the  colours  in  the 
spectrum.  The  former  condition  may  be  present  with  complete 
power  of  discrimination  between  the  different  parts  of  the  spectrum 
which  are  visible.  Thus  in  normal  individuals  the  limit  of  the  visible 
red  spectrum  is  between  X  760  and  \  780.  In  a  certain  number 
of  cases  it  is  found  that  the  spectrum  is  not  visible  beyond  \  700 
with  bright  light,  or  beyond  \  620  with  dim  light.  Such  cases  may 
be  said  with  truth  to  suffer  from  red  blindness,  and  they  will  be 
unable  to  see  a  red  lantern  or  appreciate  its  colour  unless  the  red 
light  is  mixed  with  a  considerable  amount  of  orange.  They  may 
be  detected  by  testing  their  power  of  mixing  colours.  A  rose  colour 
consists  of  a  mixture  of  a  violet  and  red  light.  In  an  individual 
with  a  shortened  red  end  of  the  spectrum  only  the  violet  element 
of  the  rose  would  be  visible,  so  that  he  would  be  inclined  to  class 
it  with  the  blues  rather  than  with  the  reds.  Cases  also  occur  in 
which  there  is  a  shortening  of  the  violet  end  of  the  spectrum,  but 
they  have  little  or  no  practical  importance. 

Of  the  second  class  of  cases,  distinguished  by  deficiency  of  power 
of  discriminating  colours,  all  grades  are  known.  A  very  large  pro- 
portion of  individuals,  as  much  as  20  per  cent.,  present  a  power  of 
distinguishing  colours  which  is  below  normal,  and  Edridge-Green 
distinguishes  these  various  classes  (calling  the  normal  person  hexa- 
chromic)  as  pentachromic,  tetrachromic.  trichromic,  and  dichromic. 
If  we  regard  a  spectrum  in  very  dim  light  it  appears  gTcy.  With  a 
slight  increase  in  luminosity  we  can  make  out  two  colours,  red  at 
one  end  and  violet  at  the  other.  On  further  increasing  the  Kiminosity 
the  spectrum  appears  trichromic,  being  composed  of  the  colours 
red,  green,  and  violet.  In  colour-blind  individuals  this  limitation 
of  the  colours  distinguished  applies  to  all  strengths  of  luminosity. 
Thus  the  dichromic  sees  only  red  and  violet,  the  trichromic  sees  red, 
green,  and  violet.  It  is  the  dichromic  cases  to  which  the  name  of 
'  colour-blind  '  has  been  chiefly  applied,  the  trichromic  cases  having 
received  the  name  of  '  anomalous  trichromats  '  (on  the  Young- 
Helmholtz  theory).     The  ordinary  '  red- blind  '  person    is    generally 


VISUAL  SENSATIONS  649 

a  dichromic  with  shortening  of  the  red  end  of  the  spectrum.  The 
'  green-blind  '  person  is  a  dichromic  without  shortening  of  the  red 
end.  It  is  an  instructive  experience  to  make  either  a  dichromic 
or  a  trichromic  mark  out  on  a  spectrum  a  monochromatic  patch. 
In  a  dichromic,  such  a  patch  at  the  red  end  will  include  red.  orange, 
yellow,  and  green.  In  a  trichromic,  red,  orange,  and  yellow  will 
probably  be  included  in  the  patch.  This  method  is  the  most 
accurate  way  of  determinin<:  diminution  of  the  power  of  colour  dis- 
crimination and  shows  with  ease  even  the  minor  degrees  of  colour 
blindness. 

CONTRAST  PHENOMENA 

Simultaneous  Contrast.  If  a  grey  disc  be  placed  on  a  piece  of 
red  paper,  and  the  whole  covered  with  tissue  paper,  the  disc  will 
take  on  a  jxreenish  tinge.  If  the  ground  colour  be  green,  the 
disc  will  appear  red ;  if  blue,  the  disc  will  appear  yellow ;  in 
fine,  whatever  be  the  ground  colour,  the  colour  of  the  disc  will  be 
complementary  to  it.  These  effects  are  spoken  of  as  simultaneous 
contrast. 

Successive  Contrast.  If,  after  gazing  steadily  for  some  time  at  a 
red  disc  on  a  white  surface,  the  eyes  be  turned  towards  a  plain  white 
surface,  a  negative  after-image  of  the  disc  is  seen  on  the  paper 
coloured  green,  i.e.  the  complementary  colour  of  the  red  disc. 
Surrounding  this  the  paper  appears  red.  If  we  look  at  the  sun 
for  some  time,  and  then  turn  our  eyes  away,  there  is  at  first  a 
positive  after-image,  and  we  see  a  bright  sun  wherever  we  look.  In 
a  short  time  this  disappears  and  gives  way  to  a  black  sun  (a  negative 
after-image).  Thus  we  may  say  that  stimulation  of  any  part  of  the 
retina  with  any  colour  is  followed  by  a  colour-sensation  referred  to 
the  same  part  of  the  visual  field  and  complementary  to  the  first. 

It  has  been  much  discussed  whether  these  phenomena  are  simply 
effects  of  judgment,  or  whether  they  are  produced  by  definite  changes 
taking  place  in  the  retina.  Helmholtz  explains  them  by  the  first 
hypothesis,  and  looks  upon  them  as  cerebral  processes.  Hering,  on 
the  other  hand,  has  extended  his  theory  so  as  to  embrace  these 
phenomena,  and  ascribes  them  to  definite  changes  in  the  retina,  or 
at  any  rate  in  the  peripheral  part  of  the  visual  mechanism.  A  corollary 
to  his  theory  that  we  mentioned  above  is  that  if  dissimilation  of  a 
visual  substance  be  excited  at  any  point  of  the  retina,  assimilation  of 
the  same  substance  is  set  up  in  the  parts  of  the  retina  immediately 
adjoining  that  point.  To  this  process  the  name  of  '  retinal  induction  ' 
has  been  given.  In  this  way  the  phenomena  of  simultaneous  contrast 
may  be  explained.  Thus  if  a  ray  of  red  light  falls  on  any  spot,  it 
may  be  supposed  to  excite  dissimilation  of  the  red-green  substance 


650 


PHYSIOLOGY 


at  this  spot.  This  sets  up  assimilation  of  the  same  substance  in  the 
adjoining  parts  of  the  retina,  and  the  red  object  is  therefore 
surrounded  with  a  green  halo,  which  at  once  becomes  evident  if  we 
increase  our  appreciation  for  slight  colour-tones  by  diminishing  the 
total  amount  of  light  by  means  of  tissue-paper. 

It  has  been  much  debated  whether  the  contrast  phenomena  depend  upon 
psychical  or  retinal  events.  There  is  no  doubt  that  the  question  must  be 
answered  in  the  latter  sense,  and  that  these  phenomena  are  quite  independent 
of  the  judgment  of  the  individual.  Tliis  is  shown  clearly  by  two  experiments. 
A  box  (Fig.  295)  is  di\'ided  into  two  long  compartments,  a  b  and  c  d.  At  a 
the  compartment  is  closed  by  a  red  glass-plate  and  at  c  by  a  blue  glass-plate. 
Apertures  are  pro\'ided  at  h  and  d  for  the  observer's  eyes.  At  -f  and  +  two 
small  grey  crosses  are  fixed  about  the  middle  of  the  compartment  on  sheets 


Purple 


Purple       Yellow  Green 

Purple 

Fig.  295. 


Purple 


of  transparent  glass.  On  looking  through  the  openings  b  and  d  and  converging 
the  ej'eballs  so  as  to  fix  the  line  o,  we  get  a  fusion  more  or  less  complete  of  the 
two  colours  red  and  blue,  so  that  the  background  appears  piu-ple  ;  or  there 
may  be  a  struggle  between  the  colours,  at  one  time  blue,  at  another  red  pre- 
dominating. To  the  judgment,  however,  there  is  one  background  and  not  two, 
and  therefore,  according  to  the  theory  of  Helmholtz,  the  grey  crosses  should 
by  contrast  both  acquire  the  same  induced  coloiu-,  which  would  be  comple- 
mentary for  purple.  But  it  is  fomid  that  the  two  crosses  are  perfectly  distinct 
in  colour,  that  which  is  seen  by  the  e3'e  against  the  blue  ground  being  yellow 
while  that  on  the  red  groimd  is  green,  showing  that  the  phenomena  of  simul- 
taneous contrast  are  peripheral  and  not  central  in  their  causation.  The  same 
fact  is  very  definitely  estabUshed  by  the  following  experiment  devised  by 
Sherrington.  The  disc  (Fig.  296)  presents  two  rings,  each  half-blue  and  half- 
black.  The  outer  ring  is  intensified  when  at  rest  by  simultaneous  contrast,  the 
black  half  being  seen  against  the  siurounding  yellow,  while  the  luminosity  of 
the  blue  half  is  increased  by  the  effect  of  the  surrovmding  black.  In  the  inner 
ring  the  blue  half  is  darkened  by  contrast  with  the  surrounding  yellow,  while 
the  black  half  is  not  evidtnt  at  all.  If  the  disc  be  rotated,  we  get  two  concentric 
rings  on  an  apparently  homogeneous  field.  It  is  found,  however,  that  the  outer 
ring  flickers  long  after  complete  fusion   has  taken   place  in   the  inner   ring. 


VISUAL  SENSATIONS  651 

showing  that  the  stimulation  of  the  retina  by  the  outer  ring  is  increased  under 
the  influence  of  contrast. 

On  this  theory  successive  contrast  phenomena  are  analogous 
to  certain  phenomena  we  have  already  studied  in  other  tissues.  If 
extensive  breaking  down  of  the  visual  stuff  has  been  occurring, 
when  the  stimulus  is  removed  there  will  be  a  swing-back  of  the 
condition  of  the  protoplasm  of  the  nerve-endings  in  the  opposite 
direction,  and  the  catabolic  will  be  replaced  by  anabolic  changes  ; 
just  as,  on  breaking  a  constant  current  that  has  been  flowing  through 
a  nerve,  the  condition  of  raised  irritability  at  tEe  cathode  gives  place 
to  a  condition  in  which  the  irritability  is  depressed  below  the  normal. 


Fig.  296. 

The  improving  effect  on  the  heart  of  stimulation  of  tht  vagus  is 
also  analogous  to  a  successive  contrast  effect.  During  stimulation 
of  the  vagus  the  breaking  down  of  the  contractile  substance  is  stopped 
or  checked,  so  that  building  up  or  anabolism  can  go  on  without 
interruption.  When  the  excitation  of  the  vagus  ceases  there  is  an 
extra  store  of  contractile  material  in  the  muscle-cells.  This  causes 
the  beat  to  be  more  vigorous,  and  we  may  say  that  the  increased 
anabolism  has  been  followed  by  a  period  of  increased  catabolism, 
just  as  strong  stimulation  of  a  part  of  the  retina  with  green  (anabolism) 
gives  rise  to  a  red  after-image  (catabolism). 

It  seems  probable  that,  as  McDougall  has  pointed  out,  the  examples 
of  simultaneous  contrast  depend  on  inhibitory  processes  analogous 
to  those  which  w^e  have  studied  in  the  spinal  cord  in  dealing  with 
reciprocal  innervation  and  the  conditions  for  the  isolation  of  any 
effective  reflex.  Just  as  the  flexor  reflex,  due  to  nocuous  stimulation 
of  the  paw,  inhibits  the  extensor  or  stepping  reflex,   by  blocking 


652  PHYSIOLOGY 

the  synapses  of  those  elements  on  the  sensory  path  which  would 
pour  their  impulses  into  the  final  common  path  of  the  extensors,  so 
stimulation  of  any  portion  of  the  retina  will  tend  to  inhibit  processes 
of  a  similar  kind  occurring  in  adjacent  parts  of  the  retina  or  their 
central  connections. 

Stimulation  of  one  part  of  the  intestine  causes  inhibition  of  the 
activity  of  the  intestine  below  the  point  of  stimulation.  If  this 
inhibition  occurred  on  both  sides  of  the  stimulated  spot  we  should  have 
a  phenomenon  exactly  analogous  to  the  process  of  simultaneous  contrast. 
In  the  same  way  the  increased  briskness  of  the  antagonistic  reflex 
which  follows  the  temporary  inhibition  accompanying  the  primary 
reflex  can  be  compared  to  the  negative  after-image  resulting  on 
prolonged  stimulation  of  any  point  in  the  retina,  while  alternating 
after-images,  positive  and  negative,  which  may  succeed  a  single 
positive  stimulation,  have  their  analogue  in  the  alternating  rhythmic 
movements  of  flexion  and  extension  of  the  two  legs  which  may  follow 
single  stimulation  of  one  of  them.  The  phenomena  of  binocular 
contrast  show  that  the  retinae  are  not  alone  concerned  in  the  pro- 
duction of  these  phenomena,  but  that  we  are  dealing  also  with  the 
central  connections  of  the  optic  nerves,  the  activities  of  which  must 
be  regulated  by  the  same  laws  as  those  determined  from  our  study 
of  the  more  lowly  activities  of  the  spinal  cord. 


SECTION    IX 

MOVEMENTS  OF  THE  EYEBALLS 

Ix  order  to  obtain  distinct  vision  of  any  object,  an  image  ui 
it  must  be  formed  on  the  fovea  centralis.  Visual  attention,  i.e. 
the  fixing  of  the  gaze  on  any  object,  involves  the  adjustment  of  the 
visual  axes  by  movements  of  the  eyeball,  in  order  that  the  image  of  the 
object  of  attention  shall  fall  on  the  central  spot  in  each  eye. 

The  eyeball  rests  on  a  pad  of  fat  surrounded  by  a  denser  capsule 
of  connective  tissue,  the  capsule  of  Tenon,  from  which  it  is  separated 
by  a  lymph  space.  Within  this  space  it  is  able  to  rotate  around  axes 
which  pass  through  a  point  almost  in  the  middle  of  the  eyeball.  These 
movements  of  rotation  are  carried  out  by  the  six  ocular  muscles,  the 
four  recti  and  the  two  obhque.  The  four  recti  muscles — ^the  superior, 
inferior,  external,  and  internal — arise  from  a  continuous  tendinous  oval 
ring  which  is  attached  at  the  back  of  the  orbit  to  the  margin  of  the  optic 
foramen  and  sphenoidal  fissure.  From  this  common  origin  the  muscles 
pass  forwards  as  flat  bands  close  to  the  walls  of  the  orbit  ;  they  come 
in  contact  with  the  eyeball  at  its  equator,  passmg  through  the  sur- 
rounding lymph  space,  and  are  attached  to  the  eyeball  about  7  mm. 
behind  the  margin  of  the  cornea,  their  positions  being  indicated  by 
their  names.  Of  these  muscles  the  internal  rectus  is  the  thickest  and 
strongest  ;  the  superior  rectus  is  the  thinnest  and  weakest. 

The  superior  obhque  muscle  arises  in  a  short  tendon  attached 
to  the  back  part  of  the  orbit  in  front  of  and  internal  to  the  optic  fora- 
men. The  muscle  runs  forwards  in  the  upper  and  inner  angle  of  the 
orbit  and  ends  in  a  round  tendon,  which  passes  through  a  fibrous 
pulley  at  the  upper  and  inner  angle  behind  the  anterior  margin  of  the 
orbit.  The  tendon  then  makes  a  sharp  bend  and  passes  outwards, 
backwards,  and  downwards  between  the  superior  rectus  muscle  and 
the  eyeball,  and  is  attached  to  the  latter  just  below  the  outer  edge 
of  the  superior  rectus,  behind  the  attachments  of  the  rectus  muscles 
and  about  half-way  between  the  anterior  and  posterior  poles  of  the 
eyeball. 

The  inferior  oblique  muscle  rises  from  the  orbital  plate  of  the 
superior  maxilla,  just  within  the  anterior  margin  of  the  orbit.  The 
muscle  forms  a  flat  band  and  passes  upwards,  backwards,  and  out- 
wards between  the  superior  rectus  and  the  wall  of  the  orbit,  and  ends 

653 


654 


PHYSIOLOGY 


et>t.sup. 


r.int 


in  a  tendinous  expansion,  which  is  inserted  under  the  external  rectus 
muscle  into  the  posterior  and  outer  part  of  the  eyeball,  somewhat 
behind  the  line  of  attachment  of  the  superior  oblique  muscle. 

In  discussing  the  actions  of  these  muscles  we  may  assume  the 
eyes  to  be  in  what  is  known  as  their  primary  position,  i.e.  with  the 
visual  axes  parallel  and  directed  to  a  point  on  the  horizon.  It  is 
evident  that  if  the  muscles  rotate  the  eyeball  about  an  axis  in  a 
plane  at  right  angles  to  the  visual  axes,  the  pupils  will  move  inwards, 
outwards,  or  in  any  direction,  but  will  not  rotate.  On  the  other  hand, 
if  the  axis  of  rotation  of  a  movement  produced  by  any  muscle  lies  in  a 

plane  which  is  not  vertical  to  the 
visual  axes,  then  the  movement  of  the 
pupil  will  be  associated  with  rotation 
of  the  eyeball.  The  first  of  these  con- 
ditions is  practically  fulfilled  by  the 
external  and  internal  rectus  muscles, 
as  is  shown  in  the  diagram  (Fig.  297). 
These  muscles  by  their  contraction  will 
move  the  pupil  directly  outwards  or 
directly  inwards.  The  axis  of  rotation 
in  the  diagram  would  run  vertically 
through  the  eyeball.  The  other  four 
muscles  produce  movements  with  axes 
of  rotation  which  are  not  at  right 
angles  to  the  visual  axis.  The  rectus 
superior,  for  instance,  produces  rotation 
round  the  axis  joining  r.suf.  and 
r.m/.,  and  will  therefore  produce  move- 
ment of  the  eyeball  upwards  and 
inwards  with  a  certain  amount  of  rotation  of  the  eyeball  on  its 
antero- posterior  diameter.  The  rectus  inferior  in  the  same  way 
moves  the  eyeball  downwards  and  inwards  with  rotation.  The  obliquus 
superior  moves  the  eyeball  downwards  and  outwards,  and  the  obliquus 
inferior  upwards  and  outwards,  in  both  cases  with  some  rotation  on 
its  antero-posterior  axis  (Fig.  298).  The  only  movements  of  the  eyeball 
therefore  which  can  be  carried  out  by  the  action  of  one  muscle,  or  by 
the  reciprocal  action  of  a  pair  of  muscles,  are  the  movements  outwards 
and  inwards,  which  are  involved  in  the  common  actions  of  convergence 
of  the  visual  axes  and  conjugate  deviation  of  both  eyeballs.  Move- 
ments upwards  or  downwards  will  require  the  co-operation  of  at  least 
two  muscles.  In  order  to  direct  the  gaze  upwards  a  contraction  of  the 
superior  rectus  which  moves  the  eyeball  upwards  and  inwards  must 
be  associated  with  a  contraction  of  the  inferior  oblique  muscle 
which    rotates  the  eyeball  upwards    and   outwards.      In  the  same 


next. 


Fig.  297.  Diagram  to  show  jjuints 
of  attachment  and  lines  of  action 
of  extrinsic  ocular  muscles. 


MOVEMENTS  OF  THE  EYEBALLS  655 

way  the  inferior  rectus  muscle  will  be  associated  with  the  superior 
oblique. 

As  we  have  seen,  four  out  of  six  muscles  when  acting  singly  cause 
rotation  of  the  eyeball  on  its  antero-posterior  axis.  The  question 
arises  whether  these  movements  of  rotation  ever  occur  under  normal 
circumstances.  This  may  be  tested  in  the  following  way  :  The  gaze 
is  first  directed  at  a  brilliant  line  of  light,  e.g.  a  straight  electric 
incandescent  filament.  The  gaze  is  then  directed  to  a  uniform  white 
surface.  On  this  white  surface  a  negative  after-image  of  the  vertical 
line  is  seen.  It  is  found  that  in  whatever  direction  the  eyes  be  turned, 
upwards,  downwards,  or  obliquely  to  right  or  left,  the  after-image 
always  retains  its  vertical  direction.  If  there  were  rotation  of  the 
eyeballs  on  their  antero-posterior 
diameters,  the  stimulated  portions 
of  the  retina,  i.e.  those  which  are  oW.LoI 
the  seat  of  the  after-image,  would 
lie  obliquely,  and  the  apparent 
direction  of  the  negative  after-  IS^ , , — • — , — ilZ — . — . ; lis.* 

"  en  iA        Oft     on    lA      1    in    Qn    Qt\        A(\  e:n 

image  would  be  also  oblique. 
We  see  therefore  that,  under 
normal  circumstances,  no  rota- 
tion of  the  eyeball  on  its 
antero-posterior    diameter    takes  >-^j 

place.      The     actions    of     the    dif-  Fig.  298.     Diagram  to  show  direction  in 

ferent      muscles      are     alwavSSO       ^^^h;;;h  PupilwUl  move  under  the  action 

ot  tne  various  ocular  muscles. 

co-ordinated  that  all  movements 

of  the  eyeballs  take  place  round  axes,  which  lie  in  a  plane  passing 
through  the  centre  of  rotation  of  the  eyeballs  and  at  right  angles 
to  the  visual  axes. 

In  man  movements  of  the  eyes  are  always  bilateral  and  take  place 
in  such  a  way  that  an  image  of  one  and  the  same  object  will  fall  on  the 
central  spot  of  each  retina.  These  movements  are  simple  in  character 
and  are  of  only  two  kinds,  viz.  : 

(1)  Movements  of  both  eyes  with  maintenance  of  parallelism  of 
the  visual  axes  ;  to  this  class  belong  the  movements  of  conjugate 
deviation  employed  in  following  the  passage  of  an  object  across  the 
field  of  vision  from  right  to  left,  or  vice  versa,  as  well  as  less  extensive 
upward  and  downward  movements  of  both  eyeballs. 

(2)  The  movement  of  convergence  of  the  axes  of  both  eyes,  which 
is  always  associated  with  accommodation  for  near  objects,  and  there- 
fore with  contraction  of  the  ciliary  muscles  and  of  the  constrictors  of 
the  pupils. 

Other  movements  can  be  effected,  but  only  with  effort.  Thus 
we  can  converge  the  axes  of  the  eyes  so  as  to  look  at  a  near  object 


656  PHYSIOLOGY 

lying  to  one  side  of  us.  Such  an  action  is,  however,  associated  with  con- 
siderable effort,  and  in  nearly  all  cases  is  replaced  by  movements  of  the 
head.  Whenever  we  wish  to  examine  an  object  closely  we  turn  the 
head  so  that  the  object  lies  between  the  two  eyes,  and  a  simple  move- 
ment of  convergence  serves  to  bring  the  image  of  the  object  on  to  the 
two  foveas  centrales. 


BINOCULAR  VISION— CORRESPONDING  POINTS 
When  we  fix  our  gaze  on  any  object,  although  an  image  of  the 
object  is  formed  on  each  retina,  the  object  appears  as  single  and  not 
as  double.  On  the  other  hand,  gentle  pressure  on  one  eyeball,  so  as  to 
shift  its  gaze  slightly  from  that  imposed  on  it  by  the  co-ordinated  action 
of  the  ocular  muscles,  at  once  causes  the  object  to  appear  double.  This 
shows  that  the  single  appearance  of  an  object  seen  with  the  two  eyes 
is  due  to  the  fact  that  the  image  from  this  object  must  fall  upon 
points  in  the  retina,  simultaneous  stimulation  of  which  produces  only 
a  single  sensation.  These  points  are  known  as  '  corresponding 
'points.'  It  is  evident  that  to  each  point  in  one  retina  only  one  point 
can  exist  in  the  other  retina  which  corresponds  to  it,  since  for  every 
position  of  the  eyes  a  luminous  point  can  only  throw  an  image  on  a 
definite  point  in  each  retina . 

Such  corresponding  points  are,  in  the  first  place,  the  central  spots  in 
each  retina.  When  we  look  at  any  spot  the  axes  of  the  above  eyes  are 
so  directed  that  the  image  of  the  spot  falls  upon  the  fovea  centralis 
of  the  two  retinae.  The  image  of  all  points  to  the  right  of  this  spot  will 
fall  on  the  nasal  side  of  the  right  retina  and  on  the  temporal  side  of  the 
left  retina,  and  vice  versa.  If  the  right  retina  were  cut  out  and  placed 
on  the  left,  the  corresponding  points  of  the  two  retinae  would  be  nearly 
over  one  another. 

This  statement  is  not  absolutely  accurate,  as  is  shown  bj'  a  careful  investiga- 
tion of  the  corresponding  points  by  means  of  the  haploscope.  In  this  instru- 
ment a  white  screen  is  placed  vertically  at  the  far  point  of  vision  of  the  eyes, 
which  are  made  somewhat  myopic  by  means  of  a  convex  lens.  Each  eye  looks 
through  a  cjdindrical  tube,  the  axis  of  which  coincides  with  the  visual  axes. 
On  each  half  of  the  white  field  is  a  mark  which,  however,  appears  single, 
since  its  image  falls  on  the  fovea  centralis  of  the  two  retinae.  If  in  the  left 
field  of  vision  a  line  be  drawn  verticallj^  upwards  from  the  mark,  and  in  the 
right  field  of  vision  another  line  vertically  dowiiwards,  the  two  lines  appear 
as  a  single  hne  passing  through  the  mark.  It  will  be  seen  that  the  upper 
half  of  the  line  is  not  absolutely  continuous  with  the  lower  half,  but  appears  to 
form  a  shght  angle  mth  it,  showing  that  the  general  statement  made  above  is 
not  absolutely  correct.  By  means  of  this  instrument  we  can  determine  the 
extent  and  situation  of  all  the  points  in  the  two  retinae  which  correspond. 
The  totality  of  all  the  points  in  space,  the  lines  from  which  to  the  eyes  will  fall 
on  corresponding  points,  is  kno^vn  as  the  horopter.  Its  determination  is, 
however,  only  of  theoretical  interest. 


MOVEMENTS  OF  THE  EYEBALLS  057 

It  might  be  thought  that  single  vision  with  the  two  eyes  was  due 
to  the  fact  that  the  nerve  fibres  from  corresponding  points  in  the  two 
retina)  pass  to  and  terminate  in  identical  nervous  structures  in  the 
brain.  This  is  not  the  case.  Sint^le  viision  is  largely  the  result  of 
experience,  and  we  can  show  by  experiment  that  both  elements  are 
present  in  the  fused  sensation  obtained  from  the  two  eyes.  Thus  if 
the  left  eye  is  directed  on  to  a  red  surface  and  the  right  eye  on  to  a 
blue  surface,  we  may  obtain  either  a  fusion  of  the  fields  with  the 
production  of  a  purple  colour,  or  a  struggle  of  the  two  fields  so  that 
the  whole  field  appears  sometimes  red  and  sometimes  blue.  In  the 
same  way  if  two  figures,  lying  side  by  side,  one  ruled  with  vertical  lines 
and  the  other  with  horizontal  lines,  be  looked  at  so  that  the  image  of 
the  right  figure  falls  on  the  right  retina  and  of  the  left  figure  on  the 
left  retina,  we  do  not  see  a  single  figure  with  the  lines  crossing  one 
another  so  as  to  form  a  network,  but  we  again  obtain  a  struggle  so 
that  first  one  figure  is  seen  with  the  vertical  lines  prominent,  and  then 
this  wanes  and  is  succeeded  by  the  other  figure  in  which  the  horizontal 
lines  are  prominent.  Which  figure  we  see  most  easily  seems  to  be 
dependent  on  the  direction  of  the  eye  movement.  If  the  eyes  are 
moved  vertically  upwards  and  dowTiwards  the  figure  with  the  vertical 
lines  comes  more  into  prominence,  while  the  figure  with  the  horizontal 
lines  is  seen  when  the  eyes  are  moved  from  side  to  side. 


42 


SECTION  X 

VISUAL  JUDGMENTS 

LOCALISATION  AND  PROJECTION.  Much  discussion  has  been 
wasted  on  the  question  why  we  see  things  upright  while  the  images 
on  our  retina  are  inverted.  The  answer  is  a  simple  one.  We  do  not 
look  at  nor  are  we  conscious  of  the  image  on  our  retina.  When 
we  say  that  we  see  anything  we  are  not  expressing  merely  a 
sensation,  but  we  are  giving  an  interpretation  of  certain  sensations 
in  the  light  of  long  experience  which  has  involved  a  large  number 
of  sensations  besides  that  of  vision.  Thus  a  new-bom  child  sees, 
i.e.  receives  images  on  its  retina  which  excite  impulses  in  the 
brain,  but  it  is  unable  to  interpret  anything  that  it  sees.  In  the 
first  few  months  there  is  indeed  no  connection  between  the  visual 
sensations  and  eye  movements  ;  it  is  only  about  the  third  month 
after  birth  that  the  child  will  follow  a  lighted  candle  or  bright  object 
with  its  eyes,  and  this  association  of  ocular  movements  with 
retinal  impressions  gradually  extends  also  to  many  other  movements. 
The  continual  and  at  first  apparently  aimless  movements  of  the 
infant  bring  in  a  flood  of  muscular  and  tactile  impressions  which  only 
after  many  trials  are  recognised  as  corres'ponding  wdth  sensations 
arriving  from  the  eyes.  It  at  first  finds  that  with  the  right  hand  it 
can  touch  objects  lying  on  the  right  side  of  the  field  of  vision.  It 
becomes  conscious  therefore,  not  of  the  left  side  of  its  retina,  but  of  a 
series  of  objects  which  have  distinct  relations  to  its  right  hand,  and  of 
a  certain  thing  seen  outside  itself.  The  projection  and  localisation  of 
visual  impressions  are  therefore  not  intuitive  or  innate  qualities 
attached  to  stimulation  of  each  point  of  the  retina,  but  are  the  result 
of  experience,  the  testing  and  comparing  of  visual  sensations  with 
tactile  and  muscular  sensations  from  all  parts  of  the  body.  From  these 
experiences  we  learn  to  associate  stimulation,  say,  of  the  right  side 
of  the  retina  with  the  presence  of  objects  lying  in  front  of  and  to 
the  left  of  the  body,  and  to  project  our  visual  sensations  in  this 
direction.  If,  for  instance,  we  press  the  finger,  with  closed  eyehds,  on 
the  outer  side  of  the  right  eyeball,  a  luminous  ring,  or  phosphene, 
will  be  seen  apparently  towards  the  left,  i.e.  the  region  whence  the 
pressed- upon  part  of  the  retina  will  be  normally  stimulated  by  rays 
of  hght. 

658 


VISUAL  JUDGMENTS 


659 


The  projection  of  visual  impressions  is  well  shown  in  Scheiner's  experiment. 
Two  needles  are  placed  one  behind  the  other  on  a  wooden  rod,  one  at  18  cm. 
and  the  other  at  a  distance  of  60  cm.  from  the  eye.  One  eye  is  closed,  and 
then  a  card  is  held  before  the  other.  In  the  card  two  small  holes  are  pierced 
by  means  of  a  needle  at  a  distance  from  one  another  less  than  the  diameter 
of  the  pupil.  On  accommodating  now  for  one  needle,  the  other  needle  appears 
double.  Thus  if  the  eyes  are  accomiiodated  for  the  distant  needle  F 
(Fig.  299,  II),  the  image  of  N  is  formed 
behind  the  retina,  and  since  only  a  very 
narrow  bundle  of  raj's  can  pass  through 
the  holes  in  the  card  two  images  of  the 
needle  are  formed  on  the  retina.  In  the 
same  way,  if  the  eye  be  accommodated 
for  the  near  needle  the  image  of  F  falls 
in  front  of  the  retina,  and  therefore  there 
will  be  again  two  images  of  it  on  the 
retina.  In  the  former  case,  if  the  hole  /3 
be  covered  with  a  card,  the  left-hand 
image  disappears.  In  the  latter  case, 
on  covering  p  the  right-hand  image  dis- 
appears, showing  that  the  apparent  posi- 
tion of  the  object  depends  on  the  relation 
of  its  image  in  the  retina  -to  the  point  of 
fixation,  i.e.  to  the  fovea  centraUs. 

JUDGMENT  OF  SIZE.  The 
apparent  size  of  an  object  is  deter- 
mined in  the  first  place  by  the 
magnitude  of  its  image  formed  on 
the  retina,  and  therefore  by  the 
visual  angle  which  the  object  sub- 
tends at  the  optical  centre  of  the 
eye,  as  will  be  evident  from  the 
diagram  (Fig.  300).  The  apparent 
size  of  any  given  object  varies  in- 
versely in  proportion  to  the  distance. 
Thus  the  size  of  an  image  on  the 
retina  of  an  object  two  inches  long  at 
a  distance  of  one  foot  is  equal  to  the 

image  of  an  object  four  inches  long  at  a  distance  of  two  feet.  An 
object  can  be  seen  if  the  visual  angle  subtended  by  it  (the  angle 
AcB  in  Fig.  300)  is  not  less  than  sixty  seconds.  This  is  equivalent  to 
an  image  on  the  fovea  centralis  about  -tyw  across,  which  is  about  the 
diameter  of  a  cone. 

The  visual  angle  is,  however,  by  no  means  the  most  important 
factor  in  our  judgment  of  size.  Thus  as  a  man  walks  away  from  us 
his  size  does  not  appear  to  vary,  although  the  visual  angle  subtended 
by  him  on  our  retina  is  continually  diminishing.  Where  the  size  of 
an  object  is  known  to  us,  as  in  the  instance  just  mentioned,  it  is  used 


Fig.  299.  Diagram  to  illustrate  Schei- 
ner's experiment. 
F,  the  far  needle ;  N,  the  near 
needle  ;  a  and  ,3,  two  pinhojes  in  a 
piece  of  card.  The  continuous  lines 
indicate  the  path  of  the  rays  for  which 
the  eye  is  accommodated. 


660 


PHYSIOLOGY 


Fig.  300. 


as  a  means  of  judging  the  size  of  surrounding  objects.  Where 
the  size  of  the  object  is  unknown  our  judgment  of  its  size  is 
determined  by  a  comparison  of  its  apparent  size,  as  judged 
from  the  size  of  the  retinal  image,  with  the  muscular  efEort  of  the 
convergence  and  accommodation  which  are  present  at  the  same  time. 
Thus  if  we  gaze  at  the  sun  for  a  minute  so  as  to  gain  a  negative 
after-image  the  size  of  this  image  will  be  constant.  Its  apparent 
size,  however,  will  vary  according  to  the  distance  of  the  surface  on  which 
we  direct  our  gaze  :  on  looking  at  a  piece  of  paper  held  near,  it  may  be 
about  one  inch  across  ;  on  looking  at  a  distant  wall,  it  may  be  several 
feet  across.     If  we  look  through  a  piece  of  coarse  wire  gauze  at  a 

distant  window,  the  meshes  of 
the  gauze  appear  to  be  in  the 
neighbourhood  of  the  window 
and  extremely  large  ;  on 
directing  the  gaze  then  to  an 
object  held  just  in  front  of 
the  wire  gauze,  the  mesh  will 
look  extremely  small.  On 
the  other  hand,  if  we  cut  out  the  movements  of  accommodation  and 
convergence  by  looking  at  a  piece  of  wire  gauze  through  a  minute 
pin-hole  in  a  card,  the  size  of  the  meshes  will  increase  as  the  gauze 
is  brought  near  to  the  eye.  In  this  case  we  judge  of  their  size  entirely 
by  the  visual  angle  they  subtend. 

In  the  muscular  elements  which  contribute  to  this  judgment  of 
size,  the  convergence  of  the  axes  is  more  important  than  the  accommoda- 
tion of  each  eye,  so  that  judgTuent  is  but  httle  affected  if  we  paralyse 
accommodation  altogether  by  dropping  atropine  into  the  eye.  The 
visual  axes  may  be  regarded  as  practically  parallel  for  any  object  at  a 
greater  distance  than  five  metres ;  for  such  obj  ects  no  act  of  accommoda- 
tion is  necessary.  In  judging  of  the  size  of  any  object  beyond  this 
distance  we  have  only  the  visual  angle  to  go  by,  which  of  course  gives  by 
itself  no  information  unless  we  know  the  distance  of  the  object.  Here 
the  obscuration  of  the  outlines  of  the  object  in  consequence  of  the 
deficient  transparency  of  the  atmosphere  plays  a  large  part  in  our  judg- 
ments and  may  be  upset  in  either  direction  by  changes  in  transparency 
of  the  atmosphere.  Thus  when  walking  on  the  Downs  in  foggy  weather 
a  gigantic  object  may  be  seen  looming  through  the  mist,  which,  on 
advancing  a  couple  of  paces,  is  seen  to  be  a  sheep.  On  the  other  hand,  in 
the  clear  air  of  the  Alps  the  traveller  continually  under- estimates  the 
size  of  distant  objects,  and  takes  a  mass  of  rocks  of  the  size  of  St.  Paul's 
for  a  traveller  wending  his  way  up  the  snow  arete. 


VISUAL  JUDGMENTS 


6G1 


ILLUSIONS  OF  SIZE 
The  distance  between  two  points  appears  longer  if  a  number  of 
points  be  interposed  between  the  two.  Thus  if  two  equal  quadri- 
lateral figures  be  divided — one  by  horizontal  and  the  other  by  vertical 
lines — the  one  divided  by  horizontal  lines  will  appear  elongated  ver- 
tically, and  that  divided 
by  vertical  lines  elongated 
horizontally  (Fig.  301). 
Apparently  it  requires  a 
somewhat  less  effort  to 
pass  directly  from  one 
point   to  the  other  than  Fro.  SOL 

when    the    gaze    has    to 

follow  an  interrupted  line.  The  eye  muscles  probably  make  a  separate 
effort  of  movement  at  each  interruption  of  the  line.  To  these  move- 
ments is  due  the  illusion  in  Fig.  302,  where  parallel  lines  seem  to  diverge 
or  converge.  Of  two  equal  lines,  one  of  which  is  vertical  and  one  hori- 
zontal, the  vertical  line  seems  the  longer.  WTien  the  eye  is  moved 
upwards,  the  tendency  of  the  superior  rectus  to  move  the  eye  inwards 
has  to  be  counteracted  by  a  pull  of  the  inferior  oblique  muscle  turning 

the  eye  outwards,  A  greater  effort 
is  therefore  required  than  when 
the  eye  is  moved  either  inwards  or 
outwards,  and  it  has  been  sug- 
gested that  it  is  this  greater 
muscular  effort  which  is  respon- 
sible for  our  over- valuation  of  the 
length  of  vertical  as  compared 
with  that  of  horizontal  lines. 

It  must  not,  however,  be 
imagined  that  an  actual  move- 
ment of  the  eyes  is  necessary  in 
order  to  judge  of  the  size  and 
distance  of  any  object.  If  a  white 
thread  be  hung  up  in  a  dark 
and  be  illuminated  for  an  instant  of  time  by  an  electric 
spark  it  is  impossible  for  an  observer  in  the  dark  room  to  move 
his  eyes  so  that  the  image  of  the  thread  shall  fall  on  the  corre- 
sponding points  of  the  two  retina)  before  the  illumination  has 
disappeared.  In  spite  of  the  fact,  however,  that  the  image  of 
the  thread  falls  on  non-corresponding  points,  as  will  be  seen  from 
the  diagram  (Fig.  303),  the  thread  is  seen,  not  as  double,  but  as 
single,  and  a  very  correct  impression  may  be  obtained  of  its  size  and 


/////////////////J 
///////////////xo 


Fio.  302. 


room 


662 


PHYSIOLOGY 


position.  In  this  judgment  or  interpretation  a  number  of  separate 
processes  must  be  involved.  The  fact  that  the  eyes  are  not  accom- 
modated for  the  thread  evokes  at  once  the  associated  movements 


L.E. 
Fig.  303.     The  eyes  are  directed  to  the  point  h.     A  thread  hung  obliquely  at  a 
under  these  circumstances  gives  rise  to  the  images  shown  in  the  upper  figures 
• — i.e..  two  images  which  do  not  lie  on  corresponding  points.     Nevertheless  the 
thread  is  seen  as  single. 

which  would  be  necessary,  if  time  allowed,  to  bring  the  non-corre- 
sponding images  on  to  corresponding  points  of  the  retina.  We  do  not 
therefore  assume  a  doubleness  of  an  object,  even  when  its  images 
fall  on  non- corresponding  points,  unless  our  gaze  is  voluntarily  directed 
on  the  object. 

THE    JUDGMENT    OF    SOLIDITY.     The    fusion    of    non-corre- 
sponding images  to  a  single  visual  conception  is  responsible  for  our 

appreciation  of  solidity.  If  we  look  at 
any  object  which  is  not  too  far  from  the 
eyes,  first  with  the  right  and  then  with  the 
left  eye,  we  shall  see  that  the  images  in 
the  two  eyes  are  not  identical.  If  we 
look,  for  instance,  at  a  truncated  pyramid, 
we  shall  see  with  the  right  eye  rather  more  of  the  right  side  of 
the  pyramid  and  with  the  left  eye  rather  more  of  the  left  side 
(Fig.  304).  If  these  two  images  a  and  h  be  so  arranged  that  they 
fall  on  corresponding  points  of  the  two  retinae,  there  is  no  confusion 
of  sensation,  but  the  resulting  impression  is  that  of  a  solid  object. 
This  is  the  principle  involved  in  the  stereoscope,  which  allows  us 
to  combine  two  images  of  this  character  so  that  they  fall  on  corre- 
sponding points  of  the  two  retinae. 


Fig.  304. 


VISUAL  JUDGMENTS 


663 


S 


In  Brewster's  stereoscope  (Fig.  305),  which  is  almost  invariably  used  at  the 
present  time,  the  combination  of  the  two  pictures  is  effected  by  means  of  two 
half-lenses  with  convex  surfaces,  and  their  thinner 
margins  directed  inwards  so  that  they  act  as  prisms. 
A  vertical  black  screen  is  placed  between  the  two 
lenses.  On  looking  through  the  lenses  towards  the 
point  s,  the  direction  of  the  rays  is  changed  by  the 
prisms  so  that  the  image  of  the  pictures  b  and  b' 
fall  on  corresponding  points  of  the  retinae — b  into 
the  left  eye  and  b'  into  the  right  eye.  The  ordinary 
photographs  for  these  stereoscopes  are  taken  by 
means  of  a  double  camera  with  lenses  at  a  distance 
apart  considerably  greater  than  that  between  the  two 
eyes.  On  this  account  there  is  actually  an  exaggera- 
tion of  the  solidity  of  the  combined  images. 


B' 

■T 


w    \ 


I 


A' 

Fio    305.     Brewster's 
stereoscope. 


When  only  one  eye  is  used  the  external 
world  has  a  much  flatter  appearance.  Some 
idea  of  solidity  is  still  gained  from  the  fact 
that  the  accommodation  has  to  be  altered  in 
order  to  bring  different  parts  of  the  sohd  objects 
into  focus.  The  judgment  is  also  aided  by  the  effects  of  light  and 
shade.  The  inadequacy  of  such  means  in  default  of  the  stereoscopic 
images  in  binocular  vision  is  at  once  appreciated  when  we  try  to 
dissect  or  to  carry  out  any  fine  manipulation  using  only  one  eye. 


SECTION  XI 

THE  NUTRITION  OF  THE  EYEBALL 

The  eyeball  is  protected  in  front  by  the  eyelids.  These  are  lined 
internally  with  a  delicate  mucous  membrane  continuous  with  the  con- 
junctiva covering  the  anterior  surface  of  the  eyeball.  This  membrane  is 
kept  constantly  moist  by  the  secretion  of  the  lacr}Tual  gland,  a  small 
acino-tubular  gland  built  up  on  the  type  of  a  serous  gland,  situated  at 
the  upper  and  outer  angle  of  the  orbit.  The  secretion,  '  the  tears,' 
has  a  shghtly  alkaline  reaction  and  contains  about  98-2  per  cent, 
water  and  1-8  per  cent,  total  sohds,  viz.  0-5  per  cent,  coagulable  protein 
and  1-3  per  cent,  inorganic  salts,  of  which  sodium  chloride  is  the  most 
important  constituent.  Since  the  tears  are  constantly  flowing  over 
the  eyes  they  serve  not  only  to  moisten  the  surface  but  to  wash  away 
any  irritant  material  or  bacteria  which  may  be  deposited  from  the 
air.  The  tears  have  a  bactericidal  power  which  is  lost  if  the  fluid  be 
boiled  for  two  or  three  minutes.  Our  knowledge  as  to  the  nervous 
mechanism  of  the  secretion  of  the  tears  is  still  incomplete.  Stimulation 
of  the  conjunctiva  evokes  an  increased  secretion  of  lacrymal  fluid 
which  can  also  be  induced  by  emotional  conditions.  It  is  stated 
that  lacrymal  secretion  can  be  produced  by  the  stimulation  of  the 
cervical  sympathetic  as  well  as  by  stimulation  of  certain  cranial  nerves 
e.g.  facial  and  fifth  nerve.  Structural  changes  analogous  to  those 
to  be  described  in  the  salivary  glands  have  also  been  found  in  the 
lacrymal  gland  as  a  result  of  secretion.  The  excess  of  fluid  is  drawn 
off  from  the  conjunctival  sac  by  the  nasal  duct,  which  leads  to  the 
nasal  cavity  on  the  same  side.  If  the  eyes  be  kept  open  for  some 
minutes,  the  conjunctiva  covering  the  eyeball  becomes  dry  and 
irritation  is  set  up.  Normally  the  membrane,  and  especially  that 
over  the  cornea,  is  kept  moist  and  transparent  by  involuntary  move- 
ments of  the  eyelids,  which  close  or  blink  about  twice  a  minute,  so 
distributing  the  lacrymal  secretion  over  the  whole  conjunctival 
surface.  This  blinking  is  a  reflex  act,  the  afferent  channels  being 
fibres  of  the  fifth  nerve,  and  the  efferent  the  fibres  of  the  facial  nerve 
supplying  the  orbicularis  palpebrarum.  It  is  spoken  of  as  the  '  con- 
junctival reflex,'  and  is  one  of  the  last  reflexes  to  disappear  in  chloro- 
form or  ether  narcosis. 

Just  below  the  mucous  membrane  of  the  lids  we  find  a  series 

664 


THE  NUTRITION  OF  THE  EYEBALL 
specialised    sebaceous    glands,    the    '  Meibomian    glands.' 


605 

of  specialised  sebaceous  glands,  the  '  Meibomian  glands.'  The 
fatty  secretion  of  these  glands  is  poured  out  at  the  edge  of  the 
lids,  keeping  these  and  the  eyelashes  greasy,  and  so  preventing 
their  being  wetted  by  the  tears.  Any  overflow  of  tears  from  the 
conjunctival  sac  is  thereby  prevented,  unless  the  secretion  becomes 
excessive  ;  so  that  the  whole  of  the  fluid  under  normal  circumstances 
is  kept  within  the  sac  and  flows  away  only  through  the  nasal  ducts. 

INTRAOCULAR  PRESSURE.     The  eyeball  is  formed  of  a  tough 
inextensible    capsule,   the   sclerotic,    filled   with   fluid   or   semi-fluid 


Fig.  306.     Arrangement  of  apparatus  for  measurement  of  intraocular  pressure. 

(Hexdersok  and  Stabling.) 

G  is  a  piston-recorder  for  recording  graphically  the  changes  in  pressure. 

contents.  In  order  that  the  eyeball  may  be  suflB.ciently  rigid  to 
maintain  the  normal  relations  of  the  various  refractive  media,  and 
to  afford  a  fixed  point  for  the  action  of  the  cihary  muscle,  this  fluid 
must  be  under  pressure.  On  connecting  a  small  manometer  with 
the  anterior  chamber,  care  being  taken  to  prevent  any  escape  of 
the  intraocular  fluid,  it  is  found  in  the  normal  eye  that  this  pressure 
is  about  25  mm.  Hg. 

The  problem  of  measuring  intraocular  pressure  is  analogous  to  that  of 
measuring  the  intracranial  pressure.  The  eyeball  represents  a  cavity  into  which 
fluid  is  continually  being  poured  and  from  which  it  is  being  absorbed,  the 
intraocular  tension  determining  the  exact  balance  between  the  processes  of 
secretion  and  absorption.  It  is  therefore  necessary  in  determining  the  amount 
of  this  pressure  to  take  care  that  no  fluid  either  enters  or  leaves  the  eyeball.  For 
this  purpose  we  can  make  use  of  the  arrangement  represented  in  the  accompany- 
ing diagram  (Fig.  .S06).  Tlae  steel  needle  A  is  connected  to  a  capillary  glass  tube, 
CB.  This  has  a  lateral  opening,  through  which  a  bubble  of  air  can  be  introduced 
into  the  tube.     By  means  of  a  T-piece  the  capillary  is  connected  with  a  water 


666  PHYSIOLOGY 

manometer  e,  and  with  a  reservoir  f,  containing  0-9  per  cent,  salt  solution.  The 
pressure  in  the  apparatus  is  now  raised  to  about  25  cm.  of  water.  While  the 
fluid  is  dropping  from  the  end  of  the  needle,  it  is  thrust  through  the  lateral 
part  of  the  cornea,  so  as  to  lie  in  the  middle  of  the  anterior  chamber.  A  bubble 
is  then  introduced  by  the  side  tube,  D,  into  the  capillary  tube,  and  the  reservoir 
adjusted  to  such  a  height  that  the  bubble  remains  stationary.  We  know  then 
that  the  pressure  inside  the  eye  exactly  balances  the  pressure  of  the  fluid  in 
the  reservoir,  and  we  have  also  provided  that  there  shall  be  no  appreciable 
escape  of  fluid  from  the  eye  or  entry  of  fluid  into  the  eye.  If  the  bubble  remains 
stationary  for  three  or  four  minutes  we  know  that  equilibrium  is  attained,  and 
we  can  read  off  the  height  of  the  intraocular  pressvire  on  the  manometer  E 
connected  with  the  reservoir. 

On  making  an  opening  into  the  cornea  the  fluid  drains  away 
and  the  eyeball  becomes  soft  and  collapsed,  the  cornea  being  folded, 
and  the  eye  being  naturally  useless  as  an  optical  instrument.  The 
fluid  which  flows  away,  and  which  forms  the  aqueous  humour  and 
also  fills  the  interstices  of  the  gelatinous  tissue  of  the  vitreous,  con- 
tains only  a  minute  trace  of  protein,  consisting,  in  every  100  parts, 
of  987  parts  water  and  1'2  to  1"3  total  soUds,  of  which  only  0*08 
to  0"12  part  consists  of  protein.  If  a  cannula  be  kept  in  the  anterior 
chamber  this  fluid  rapidly  alters  its  character,  becoming  coagulable, 
and  containing  3  to  4  per  cent,  of  proteins. 

The  intraocular  fluid  is  continually  being  renewed.  The  eyeball 
receives  a  rich  vascular  supply,  which  forms  a  close  network  of  vessels 
and  capillaries  in  the  choroid  coat,  with  its  prolongations  the  ciHary 
processes  and  iris.  The  chief  seat  of  formation  of  the  intraocular 
fluid  is  the  ciliary  processes.  Here  there  is  a  constant  transudation 
of  fluid  from  the  blood-vessels  into  the  anterior  part  of  the  vitreous 
cavity,  the  amount  of  the  transudation  varying  with  the  pressure 
in  the  blood  capillaries  (Fig.  307),  being  increased  by  any  rise  in  the 
capillary  blood  pressure  or  by  any  fall  in  the  intraocular  pressure. 
Of  the  fluid  poured  out  by  the  ciHary  processes  a  very  small  propor- 
tion (perhaps  one-fiftieth)  passes  backwards  into  the  vitreous  humour 
and  gradually  drains  out  of  the  eyeball  by  the  lymphatic  spaces  of 
the  optic  nerve.  By  far  the  larger  amount  passes  forward  through 
the  fibres  of  the  suspensory  Ugament  into  the  posterior  chamber  (the 
annular  cavity  between  the  iris  in  front  and  the  lens  and  ciliary 
processes  behind),  and  thence  round  the  margin  of  the  iris  into  the 
anterior  chamber.  From  the  anterior  chamber  it  passes  into  the 
spaces  of  Fontana  at  the  outer  angle  of  the  chamber,  whence,  under 
pressure,  it  can  filter  slowly  between  the  endothelial  cells  lining  the 
canal  of  Schlemm  into  this  vessel  and  so  drain  away  into  the  venous 
system.  A  considerable  resistance  is  offered  to  the  passage  of  fluid 
into  the  canal  of  Schlemm.  Hence  the  constant  transudation  of 
fluid  from  the  ciliary  processes  raises  the  intraocular  pressure  to 
25  mm.  Hg,  and  a  continuous  production  of    about  6  cubic  milli- 


THE  NUTRITION  OF  THE  EYEBALL  667 

metres  of  fluid  per  minute  suffices  to  maintain  the  pressure  at  this 
height. 

If  the  formation  of  intraocular  fluid  be  increased  by  rise  of  blood 
pressure,  the  intraocular  pressure  must  also  rise  until  a  point  is 
reached  at  which  the  increased  filtration  through  the  anterior  angle 
is  just  equal  to  the  increased  production  resulting  from  the  rise  of 
blood  pressure.     Within  wide  limits  therefore  the  intraocular  pressure 


I.O.P. 

1^          \ ^                                                   37 

Art.  B.P. 

mm.  Hg. 
mm.  Rz, 

100                                                f      f 

I' 

P             Q        R            S 

10  sec. 

\                 \         \               \ 

mm.  Hg 


mm.  Hg. 


Fig.  307.  Curve  showing  effects  on  the  intraocular  pressure  (in  the  dog)  of 
mechanical  interference  with  the  circulation.  Blood -pressure  measured  in 
left  carotid,  intraocular  pressure  in  right  eye.  From  p  to  s  the  descending 
thoracic  aorta  was  occluded.  From  Q  to  r  the  right  vertebral  and  sub- 
clavian arteries  were  also  occluded.     (Henderson  and  Starling.) 


varies  with  the  blood  pressure.     This  is  shown  by  the  following  records 
of  both  pressures  in  different  animals  (Henderson  and  Starling) : 


Arterial  pressure 

128  mm.  Hg. 

158  mm.  Hg. 

180  mm.  Hg. 

70  mm.  Hg. 


Dog 


Intraocular  pressure 
26  mm.  Hg. 
34  mm.  Hg. 
40  mm.  Hg. 
23  mm.  Her. 


Conversely  the  intraocular  pressure  may  be  altered  by  increasing 
or  diminishing  the  ease  with  which  the  fluid  escapes  through  the 
filtration  angle.  If  the  anterior  angle  becomes  blocked  as  the  result 
of  inflammatory  changes,  or  other  causes,  the  intraocular  pressure 
rises  gradually  until  it  attains  a  height  far  above  normal.  The 
eyeball  to  the  finger  feels  stony  hard,  and  the  increased  pressure 


668  PHYSIOLOGY 

afEects  seriously  the  circulation  of  blood  through  the  retinal  vessels, 
so  that  atrophy  of  the  retina  is  produced  together  with  disturbance 
of  the  nutrition  of  the  whole  eyeball.  This  condition  of  raised  intra- 
ocular tension  occurs  in  the  disease  known  as  glaucoma. 

The  constant  renewal  of  the  intraocular  fluid  is  important  not 
only  for  the  maintenance  of  the  intraocular  pressure  but  also  for 
the  nutrition  of  the  structures,  such  as  the  lens,  suspensory  ligament, 
and  vitreous  humour,  which  do  not  receive  any  vascular  supply. 


THE  ORGANIC  SENSATIONS 

SECTION  XII 

SENSATIONS  OF  MOVEMENT  AND  POSITION 

In  studying  the  phenomena  of  reflex  movements,  as  presented  by 
the  spinal  animal,  our  attention  was  drawn  to  the  importance  of 
the  afferent  impulses  transmitted  to  the  central  organ  by  means  of 
a  special  system  of  sense-organs,  called  by  Sherrington  the  proprio- 
ceptive system.  These  afferent  impressions  intervene  at  a  later  period 
in  every  reflex  action  than  do  the  initiating  sensory  (exteroceptive) 
impulses.  They  arise  as  a  result  of  the  reflex  movement  itself,  and 
serve  to  regulate  the  extent  of  this  movement  as  well  as  the  co- 
ordinated changes  in  the  other  muscles  of  the  body.  Whether  they 
be  synergic  or  antagonistic,  the  abolition  of  the  impulses  arising  in 
this  system  has  an  effect  similar  to  that  of  the  destruction  of  the 
governor  of  an  engine.  The  movements  excited  by  peripheral  stimu- 
lation become  excessive  and  conflicting  ;  there  is  no  longer  the  give- 
and-take  of  the  antagonistic  muscles  surrounding  the  joint,  and  the 
result  is  a  state  of  disorder  and  inco- ordination,  termed  ataxy. 

Of  the  proprioceptive  impulses  a  certain  proportion  reach  the 
cerebral  cortex  and  arouse  states  of  consciousness  which  we  speak 
of  as  sensations  of  position,  movement,  or  resistance,  and  which 
form  the  basis  of  judgments  as  to  these  conditions.  In  conscious- 
ness they  are  contrasted  with  the  sensations  arising  from  the  other 
sense-organs  in  the  same  way  as  they  are  in  the  subconscious  regula- 
tion of  the  motor  adaptations  of  the  body.  All  the  senses  which  we 
have  so  far  considered  give  us  information  of  thhigs,  i.e.  of  a  material 
world  which  can  afiect  ourselves,  but  which  we  conceive  of  as  existing 
altogether  apart  from  our  sensations  of  it.  Indeed  the  visual  and 
auditory  sensations  we  project  to  distances  remote  from  the  body. 
The  sensations,  on  the  other  hand,  which  are  aroused  through  the 
intermediation  of  the  proprioceptive  system  we  refer  entirely  to 
ourselves.  By  them  we  receive  information  of  the  condition  of  the 
material  '  me,'  i.e.  of  ourselves  as  things  apart  from  the  objects 
which  surround  us  and  the  changes  in  which  ordinarily  excite  our 
activity. 

669 


670  PHYSIOLOGY 

Consciousness  we  have  seen  to  be  developed  in  proportion  to  the 
differentiation  of  the  educatable  association  centres,  which  are 
responsible  for  our  powers  of  ideation,  and  by  means  of  which  the 
different  reflex  movements  which  we. call  volitional  are  carried  out, 
guided,  augmented,  or  inhibited,  according  to  the  past  experience 
of  the  individual.  Volitional  movement  is  therefore  a  movement 
determined  by  previous  neural  events,  of  which  a  part  at  any  rate  is 
represented  in  consciousness  as  feeling,  emotion,  or  desire.  Where  an 
act  is  involuntary,  i.e.  does  not  need  the  guidance  of  experience,  indi- 
vidual or  racial,  for  its  performance,  the  afferent  impulses  which  arouse 
it  are  also,  as  a  rule,  devoid  of  representation  in  consciousness.  Thus 
we  have  no  sensation  of  the  passage  of  a  bolus  along  the  oesophagus. 
The  proprioceptive  impulses  also  only  affect  consciousness  where 
they  are  necessary  for  the  guidance  of  volitional  movement.  The 
tactile  and  gustatory  impressions  from  the  tongue  have  a  very  full 
representation  in  consciousness.  VoUtion,  however,  only  interferes 
for  the  rejection  or  acceptance  of  the  food  taken  into  the  mouth, 
and  is  not  required  for  the  minute  direction  of  the  movements  of 
mastication  and  deglutition.  The  muscular  sensibility  of  the  tongue, 
and  therefore  our  voluntary  control  of  its  movement,  is  extremely 
slight,  although  there  must  be  a  continual  flow  of  afferent  impressions 
from  the  tongue  to  the  lingual  motor  centres  to  guide  the  complex 
movements  both  of  mastication  and  deglutition.  In  the  case  of  the 
palate  muscles,  as  of  the  oesophagus,  muscular  sensibility  is  entirely 
wanting. 

It  has  been  suggested  that  afferent  impressions  from  the  muscles 
can  play  only  a  subordinate  part  in  our  sensations  of  movement,  since 
we  are  not  aware  of  the  part  taken  by  each  individual  muscle  in  any 
given  movement.  Such  a  statement  is  absurd.  We  have  no  objective 
phenomenal  experience  of  our  muscles.  All  that  we  are  aware  of 
and  can  judge  of  by  our  other  senses  is  the  movement  as  a  whole, 
and  our  sensation  of  movement  is  therefore  referred  to  the  whole 
movement  and  not  to  the  individual  muscles. 

The  sensations  arising  in  the  proprioceptive  system  can  be 
divided  into  two  main  classes  : 

(1)  The  sensation  of  the  relative  positions  of  parts  of  the  body. 

(2)  The  sensations  which  inform  us  of  the  position  of  the  head, 
with  regard  to  its  surroundings,  i.e.  with  regard  to  the  direction 
of  the  pull  of  gravity.  (It  must  be  remembered  that  *  downwards  ' 
always  means  towards  the  centre  of  the  earth,  '  upwards  '  away 
from  the  centre  of  the  earth,  i.e.  against  the  gravitational  forces.) 
This  orientation  sense  depends  on  the  integrity  of  a  special  sense- 
organ  contained  in  the  labyrinth  of  the  internal  ear.  It  is  therefore 
sometimes  spoken  of  as  the  labyrinthine  sense. 


SENSATIONS  OF  MOVEMENT  AND  POSITION  671 

THE  SENSE   OF   RELATIVE  POSITION,   INCLUDING   THE 
MUSCULAR  SENSE 

Without  using  our  eyes  we  are  able  at  any  moment  to  tell  the 
position  of  our  limbs.  If  one  arm  be  moved  passively  into  any 
position  we  can  without  difficulty  move  the  other  arm  into  an  exactly 
similar  position.  We  thus  know  the  extent  to  which  we  move  the 
limb  and  the  static  position  attained  as  the  result  of  the  movement. 
If  the  movement  is  resisted,  we  are  able  to  adjust  the  force  of  the 
muscular  contraction  to  the  resistance,  and  to  form  therefore  a  fair 
idea  as  to  the  strength  of  the  resistance. 

(a)  PASSIVE  MOVEMENTS.  A  large  number  of  different  sense- 
organs  contribute  to  the  formation  of  these  judgments.  In  the 
appreciation  of  passive  movement  the  chief  end-organs  involved  are 
those  in  connection  with  the  joints  and  their  Hgaments,  though  it 
is  probable  that  the  deeper  sense-organs  in  the  soft  parts  around 
the  joints  also  contribute  to  the  total  sensation.  Cataneous  sensa- 
tions apparently  play  but  little  part  in  the  judgments  of  passive 
movement.  It  is  true  that  the  alternating  movements  of  the  hind 
limbs,  which  occur  in  a  spinal  animal  when  it  is  held  up  by  the  hands 
under  the  fore  hmbs,  are  started,  partly  at  any  rate,  by  the  stretching 
of  the  skin  of  the  thighs  ;  but  this  effect  is  one  rather  of  initiation  of 
movement,  and  can  hardly  be  regarded  as  proprioceptive  in  character. 

The  strength  of  the  sensation  of  passive  movement  depends 
on  the  extent  of  the  movement  as  well  as  on  the  rate  with  which 
it  is  carried  out.  The  deUcacy  of  perception  varies  in  different 
joints.  Thus  in  some  joints  a  movement  of  0"25°  per  second  is 
appreciated  as  a  movement,  while  in  other  joints  the  movement  must 
be  as  extensive  as  r4°  per  second.  It  is  more  easily  appreciated  when 
the  joint  surfaces  are  pressed  together  than  when  they  are  pulled 
apart,  showing  that  the  nerve-endings  in  the  joint  surfaces  play  a 
part  in  the  origination  of  the  sensations. 

(6)  THE  SENSE  OF  MOVEMENT  (MUSCULAR  SENSATION). 
This  term  is  appUed  to  those  sensations  by  which  we  judge  of  the 
extent  and  force  of  any  active  movement  which  we  may  have  carried 
out.  Many  authors  have  ascribed  an  important  part  in  this  act 
of  judgment  to  the  so-called  '  sense  of  innervation,'  i.e.  a  sense  of 
the  actual  energy  which  is  being  discharged  from  the  motor  cells 
of  the  central  nervous  system  to  the  muscles,  and  have  thought 
that  when  we  raise  a  weight  we  judge  of  its  amount,  not  by  the 
degree  of  stretching  of  the  muscle  or  pressure  on  sensory  nerves  in 
the  muscle,  but  by  the  amount  of  force  we  voluntarily  put  out  to 
raise  the  weight.  The  fact,  however,  that  we  can  judge  of  weights, 
when  the  muscles  are  made  to  contract  by  electrical  stimuli  and  not 


672 


PHYSIOLOGY 


by  voluntary  impulses,  shows  that  this  sense  is  in  large  part,  if  not 
entirely,  peripheral.  It  is,  however,  very  complex  in  nature,  and 
is  served  by  a  whole  array  of  different  end-organs  in  the  skin,  joints, 
tendons,  and  muscles.  The  muscles  themselves  are  known  to  be 
well  suppUed  with  afferent  nerves.      Stimulation  of  the  central  end 


pr.e. 


Fig.  308.     A  neuro-muscular  spindle  of  the  cat.     (Ruffini.) 
c,  capsule  ;  -pr.e,  primary  ending  ;  s.e,  secondary  ending  ;  fl.e,  plate  ending 
(all  these  are  probably  sensory  in  function). 


V 


Fig.  309.     Part  of  a  muscle -spindle  more  highly  magnified. 
n,  nerve-fibres  passing  to  spindle  ;    a,  annular  endings  of  axis  cylinders  ; 
s,  spiral  endings  ;    d,  dendritic    endings  ;    sh,  connective-tissue  sheath  of 
spindle.     (RuFFiNi.) 

of  a  muscular  nerve  may  reflexly  excite  or  inhibit  movements  of 
other  muscles.  Sherrington  has  shown  that,  after  section  of  the 
motor  roots,  over  one-third  of  the  fibres  in  a  muscular  nerve  remain 
undegenerated,  proving  their  connection  with  the  posterior  root 
ganglia.  The  sensory  nerve-endings  in  the  muscle  are  represented 
partly  by  the  tendon  nerve-endings  and  partly  by  the  muscle-spindles. 
The  former  are  richly  branched  end-arborisations  of  nerve  fibres 
on  the  surface  of  the  tendon  bundles.  The  muscle-spindles  consist 
of  one  or  more  muscle  fibres,  often  continuous  with  normal  fibres, 
enclosed  in  a  sheath  composed  of  several  layers  of  fibrous  tissue  with 


SENSATIONS  OF  MOVEMENT  AND  POSITION         673 

intervening  lymph-spaces.  One  or  more  nerve  fibres  pierce  this 
sheath  and,  after  making  many  spiral  turns  round  the  muscle  fibres, 
branch  freely  and  terminate  in  little  knobs  on  the  surface  of  the 
fibres  (Fig.  308,  309) .  The  cross-striation  of  the  muscle  fibres  within 
the  spindle  is  but  faintly  marked.  It  is  evident  that  the  continuity 
of  these  sense-organs  with  the  contracting  muscle  ensures  in  the  best 
possible  way  that  the  organs  should  be  affected  by  the  slightest  change 
of  tension  of  the  muscle,  and  should  transmit  information  of  the  state 
of  tension  to  the  central  nervous  system. 

THE  PSYCHOLOGICAL  SIGNIFICANCE  OF  SENSATIONS  OF 
MOVEMENT.  Not  only  are  these  organic  sensations  of  importance 
as  affording  us  information  of  the  condition  of  our  own  bodies  as 
distinct  from  the  objects  in  the  world  around,  but  they  enter  into 
and  qualify  our  judgments  derived  from  all  the  sensations  which 
arise  in  the  special  sense-organs. 

When  we  regard  the  continuous  aimless  activity  of  a  healthy 
baby,  we  see  that  all  ideas  of  space,  of  extension,  of  relative  position 
are  wanting,  or  at  any  rate  are  not  present  to  guide  the  movements. 
Bit  by  bit  muscular  experience  is  acquired.  The  child  learns  that  a 
given  movement  of  the  right  arm  will  bring  the  hand  in  contact 
with  something  which  is  exciting  the  left  side  of  his  retina.  The 
surface  of  the  thing,  if  of  sufficient  extension,  can  excite  tactile 
sensations  in  all  the  fingers  of  the  right  hand.  By  moving  one  finger 
over  the  object  the  tactile  sensations  are  found  to  be  continuous  ; 
by  moving  the  whole  hand  forwards  the  thing  is  found  to  possess 
extension  in  a  direction  away  from  the  body,  and  therefore  in  the 
third  plane  of  space.  Thus  gradually  is  acquired  not  only  ideas 
of  extension,  distance,  and  space,  but  certain  movements  are  cor- 
related with  stimulation  of  definite  regions  of  the  skin  or  of  the  retina. 
Tactile  and  retinal  impressions  therefore  acquire  local  sign,  and 
power  is  acquired  of  moving  the  limbs  to  a  degree  and  in  a  direction 
adapted  to  stimuli  arising  from  any  part  of  the  tactile  or  retinal 
surfaces.  The  child  gradually  acquires  the  power  of  following  a 
bright  object  with  its  eyes,  i.e.  of  contracting  the  ocular  muscles 
so  as  to  keep  the  retinal  image  of  the  object  on  the  fovea 
centralis,  and  up  to  adult  age  we  are  still  engaged  in  this  balancing 
of  nmscular  movement  against  sense  impressions — a  balancing 
in  which  the  muscular  sensations  are  the  constant  guide  and 
criterion  of  success.  Only  by  the  muscular  sensations  are  we 
informed  whether  our  willed  movement  has  been  carried  out  or  not. 
It  is  in  virtue  of  the  muscular  and  allied  sensations  that  we  are 
able  to  clothe  our  visual  and  tactile  sensations  with  properties  of 
extension,  solidity,  and  resistance,  which  create  them  in  consciousness 
as  parts  of  a  material  world. 

43 


SECTION  XIII 

THE  LABYRINTHINE  SENSATIONS 

Throughout  almost  the  whole  of  the  animal  kingdom,  and  in 
practically  all  freely  moving  metazoa,  we  find  a  sense-organ 
which  has  often  been  designated  as  an  auditory  organ.  This 
organ,  which  is  situated  in  the  integument,  is  in  the  form  of 
a  small  sac  generally  open  to  the  exterior,  and  lined  by  cells  pro- 
vided with  hairs  and  richly  supplied  with  nerves.  Kesting  among 
the  hairs  is  a  small  concretion,  generally  of  carbonate  of  lime,  which 
is  known  as  an  otoUth.  These  sacs  have  generally  been  regarded 
as  auditory  in  function,  hence  the  term  otolith  applied  to  the  con- 
cretion. The  evidence  for  audition,  i.e.  the  power  of  appreciating 
vibrations  in  the  elastic  medium  surrounding  them,  is  scanty.  Thus 
in  fishes  this  power  has  been  stated  to  be  absent  unless  the  vibrations 
are  of  sufficient  amplitude  to  affect  the  sense-organs  of  the  skin.* 
On  the  other  hand,  there  is  evidence  that  these  otolith  organs  are 
connected  with  equilibration.  Section  of  the  nerves  going  to  them 
in  the  crayfish  causes  disturbance  of  locomotion.  Steinach  has 
succeeded  in  the  crayfish  in  replacing  the  concretion  by  a  small  particle 
of  iron.  The  animal's  behaviour  and  movements  were  perfectly 
normal  until  it  was  brought  within  a  powerful  magnetic  field.  Under 
the  influence  of  this  field  the  effect  of  gravity  on  the  iron  particle 
was  annulled  and  replaced  by  a  force  of  attraction  in  another  direction, 
ghid  the  effect  was  at  once  seen  as  pronounced  disorders  of  locomotion, 
the  animal  swimming  in  an  abnormal  position. 

From  a  sac,  such  as  that  present  throughout  the  lower  animals, 
the  organ  of  hearing  in  the  higher  vertebrata  is  developed.  Arising 
as  a  pit  in  the  epiblast  in  the  neighbourhood  of  the  hind-brain,  the 
auditory  sac  becomes  shut  off  from  the  exterior,  and  then,  by  an 
outgrowth  in  various  directions,  forms  the  complex  membranous 
labyrinth  of  the  internal  ear.  This  membranous  labyrinth,  as  we 
have  seen,  can  be  divided  into  two  parts,  viz.  the  canalis  media 
of  the  cochlea  in  front,  and  the  saccule,  utricle,  and  semicircular 
canals  behind.  The  canahs  media  of  the  cochlea  is  concerned  with 
the  reception  and  analysis  of  sound  waves.     In  the  lower  vertebrates 

*  On  the  other  hand,  Piper  has  succeeded  in  detecting  an  electrical  variation 
in  the  eighth  nerve  of  fishes  in  response  to  a  sound  stimulus. 

674 


THE  LABYRINTHINE  SENSATIONS  675 

ill  which  auditory  sensations  are  wanting  the  cochlea  is  absent, 
and  in  fishes  is  represented  merely  by  a  small  diverticulum  known 
as  the  lagena.  With  the  development  of  air-breathing  vertebrates 
we  see  the  first  signs  of  a  special  organ  of  hearing.  Thus  a  primitive 
cochlea  is  present  in  the  amphibia,  and  especially  in  the  anura,  and 
in  some  of  the  reptiles  as  well  as  in  birds  it  acquires  a  bend  and  shows 
the  beginning  of  a  spiral  arrangement.  Only  in  the  mammals  does 
it  attain  a  degree  of  development  at  all  comparable  with  that  found 
in  man,  and  characterised  by  the  formation  of  one  and  a  half  to  four 
spiral  tmns  in  the  cochlea  as  well  as  in  the  canalis  media. 

This  development  of  auditory  functions  cannot  involve  any 
abrogation  of  the  important  part  played  by  the  otolith  organ  through- 
out all  the  lower  classes  of  the  animal  kingdom.  In  man,  as  in  the 
crayfish,  it  is  the  otolith  organ  which  determines  his  behaviour 
in  relation  to  the  force  of  gravity,  and  is  therefore  responsible  not 
only  for  the  maintenance  of  equilibrium  but  also  for  the  sensations 
which  enable  him  consciously  to  orientate  himself  and  to  know 
the  position  in  which  he  happens  to  be  at  any  given  moment. 
With  the  increasing  importance  of  visual  sensations  in  deter- 
mining the  behaviour  of  the  animal,  close  connections  are  established 
between  the  central  connections  of  the  nerves  running  from  the 
otolith  organ  and  the  parts  of  the  brain  concerned  with  the  innerva- 
tion of  the  eye  muscles.  By  this  means  the  position  of  the  eyes 
is  constantly  adapted  to  the  position  of  the  head. 

The  auditory  part  of  the  internal  ear  has  already  been  described. 
That  part  of  the  labyrinth  which  represents  the  primitive  otoHth 
organ  consists  of  a  bony  framework  containing  perilymph,  in  which 
is  contained  the  membranous  lab}'Tinth  with  the  endings  of  the 
vestibular  division  of  the  eighth  nerve.  The  osseous  labyrinth 
consists  of  a  cavity,  the  vestibule,  into  which  open  behind  the  three 
bony  semicircular  canals.  In  the  vestibule  are  contained  two  little 
membranous  sacs,  the  utricle  and  saccule,  the  cavities  of  which  are 
connected  by  means  of  the  saccus  endolympJiaticus.  Into  the  utricle 
open  the  three  semicircular  canals,  the  three  canals  having  five 
openings.  These  semicircular  canals  are  arranged  in  three  planes, 
each  of  which  is  at  right  angles  to  the  other  two,  so  that  in  the  organ 
are  represented  the  three  planes  of  space.  We  may  distinguish  on 
each  side  an  external  or  horizontal  canal,  an  anterior  or  superior 
vertical  canal,  and  a  posterior  vertical  canal.  The  two  outer  canals 
lie  always  exactly  in  the  same  plane,  which  is  practically  horizontal 
in  the  normal  position  of  the  head.  Each  posterior  vertical  canal  lies 
in  a  plane  which  is  parallel  to  that  of  the  superior  vertical  canal  of  the 
opposite  side.  We  thus  see  that  these  semicircular  canals  form 
together  three  planes — one  horizontal  and  two  vertical,  the  two  latter 


676 


PHYSIOLOGY 


being  at  right  angles  to  one  another  (Fig-  310).  The  membranous 
canal  lies  within  the  osseous  canal,  a  considerable  space  inter- 
vening between  the  two  canals.  At  one  end  the  osseous  canal 
is  dilated  and  the  membranous  canal  undergoes  a  corresponding 
dilatation  so  as  to  fill  up  the  whole  bony  canal.  In  this  dilatation, 
which  is  known  as  the  ampulla,  we  find  the  ending  of  a  branch  of 
the   vestibular  nerve  in  a  special    sense    epithelium,    forming    the 


Flu.  310.     Figure  fruni  Ewald  showing  the  .situation  of  the  three  semi- 
circular canals  in  the  skull  of  the  pigeon. 


crista  acustica  (Fig.  311).  The  crista  is  composed  of  hair-cells  with 
sustentacular  cells  between  them.  The  fibres  of  the  vestibular  nerve 
end  in  arborisations  among  the  hair-cells,  the  hairs  of  which  project 
into  the  endolymph  filling  the  ampulla.  In  the  utricle  and  saccule 
we  also  find  special  sense-organs,  known  as  the  macula  acustica, 
the  structure  of  which  is  very  similar  to  that  of  the  crista  in  the 
ampullae.  Among  the  hairs,  however,  of  the  macula  is  found  a 
small  concretion  of  carbonate  of  lime,  the  otolith. 

The  first  accurate  experimental  investigation  of  the  functions 
of  these  different  parts  we  owe  to  Flourens.  This  observer  showed 
that,  whereas  extirpation  of  the  cochlea  caused  deafness,  extirpation 


THE  LABYRINTHINE  SENSATIONS 


677 


of  the  vestibule  and  semicircular  canals  left  the  auditory  sense  intact, 
but  caused  marked  disorders  of  equilibration.  That  the  peculiar 
arrangement  of  the  semicircular  canals  in  the  three  planes  of  space 
was  connected  in  some  way  with  the  functions  of  these  structures 
was  also  indicated  by  Flourens'  observation  that  destruction  of  tlie 
horizontal  canals  on  each  side  gave  rise  to  continual  nodding  move- 
ments of  the  head  in  the  plane  of  the  injured  canals.  By  many 
physiologists    the    results    obtained    by    Flourens    were    as(;ribed    to 


FiQ.  311.     Eud-organ  of  vestibular  nerve  in  ampulla  of  semicircular  canal 
('  crista  acustica  '). 

continued  irritation  of  the  peripheral  sense-organs  or  of  the  central 
parts  of  the  brain  in  consequence  of  the  lesion.  The  accurate  experi- 
ments of  Goltz,  and  especially  those  of  his  pupil  Ewald,  showed 
that  these  efiects  might  last  twelve  to  eighteen  months,  or  be  per- 
manent, and  must  therefore  be  regarded  as  an  Ausfnllserscheinung, 
i.e.  as  due  to  abolition  of  a  fimction  and  not  to  the  arousing  of  a 
function  by  abnormal  stimulation. 

Most  of  the  experiments  on  this  subject  have  been  carried  out  on 
pigeons  on  account  of  the  easy  accessibility  of  their  semicircular  canals. 
Confirmatory  observations  have,  however,  been  made  on  mammals. 
After  destruction  of  all  the  canals  or  of  the  whole  membranous 
labyrinth   on   both  sides,   disturbances   of ,  equilibrium   are   aroused 


678 


PHYSIOLOGY 


whicli  may  last  for  a  considerable  time.  The  animal  can  neither 
stand,  nor  j&y,  nor  maintain  any  fixed  attitude,  but  is  constantly 
moving  about  incoherently  and  often  so  violently  that  it  is  necessary 
to  pad  its  cage  in  order  to  prevent  it  from  injuring  itself.  Although 
the  movements  are  so  violent,  very  little  guidance  suffices  to  stop 
them  altogether.  Any  support  given  by  the  hand  enables  the  animal 
to  rest  quietly.  After  some  months  these  disorders  gradually  dis- 
appear, and  the  animal  learns  to  guide  its  movements  by  sensa- 
tions of  touch  and  sight  alone  ;  but  they  are  instantly  brought 
back    in    all    their    severity    if    the    eyes    be    bandaged,   so    as   to 

deprive  the  co  -  ordinating 
centres  of  the  guiding  visual 
sensations. 

The  same  effect  is  pro- 
duced if  that  part  of  the 
brain  which  alone  is  educat- 
able,  viz.  the  cerebral  cortex, 
be  excised.  Extirpation  of 
the  cerebral  hemispheres  in 
pigeons  causes  no  disorders 
of  equilibrium,  but  extirpa- 
tion, after  destruction  of  the 
labyrinth,  brings  back  the 
disorders  which  were  noted 
during  the  first  days  after 
operation,  and  these 
disorders  are  now  permanent. 
Recovery  even  in  the  presence  of  the  cerebral  hemispheres  is, 
however,  never  really  complete.  Although  the  animal  may  be  able 
to  walk  and  fly  very  fairly,  it  sufEers  from  a  loss  of  power  and 
loss  of  tone  which  afEect  all  its  muscles,  but  especially  those 
moving  the  trunk  and  neck.  If  the  labyrinth  has  been  extirpated 
only  on  one  side,  then  this  loss  of  tone  is  noticed  chiefly  on  the 
opposite  or  contralateral  side  of  the  body  (Fig.  312).  Loss  of  tone 
after  complete  destruction  is  well  shown  in  the  following  experiment 
devised  by  Ewald  : 

A  small  lead  bullet  is  hung  up  by  a  thread  to  the  beak  of  the 
pigeon.  As  the  bird  moves  about  the  bullet  swings,  the  head  following 
its  movements  ;  finally  the  bullet  happens  to  fall  over  the  beak 
of  the  animal — the  head  is  now  found  to  be  fixed  in  the  position  shown 
in  the  figure  (Fig.  313).  The  anterior  muscles  of  the  neck  are  too 
weak  and  toneless  to  restore  the  head  to  its  normal  position  against 
the  weight  of  the  bullet.  No  such  phenomena  are  presented  by  a 
normal  bird. 


Fig.  312.     Abnormal    posture   of   pigeon, 

which  the  labyrinth  had  been  extirpated  on    ^\^q 
one  side  five  days  previously.     (Ewald.) 


THE  LABYRINTHINE  SENSATION'S  679 

The  same  absence  of  tone  is  seen  in  maninials.  A  dog  with  both 
labyrinths  destroyed  may  jump  down  from  a  table  once,  but  will 
not  repeat  the  experiment,  since  the  muscles  of  the  fore  Umbs  are 
too  toneless  to  support  the  head  against  the  shock  of  the  jump,  and 
he  knocks  his  head  against  the  ground  as  his  legs  collapse  under 
liim.  If  only  one  canal  be  put  out  of  action,  as,  for  instance,  by 
stopping  it  with  dentist's  amalgam,  the  head  is  thrown  into  oscilla- 
tions in  a  corresponding  plane,  or  perhaps  rather  we  should  say  that 
when  the  head  oscillates  in  this  plane  there  are  no  corresponding 
sensations  set  up  which  tend  to  inhibit  the  movements.  The  same 
efiect  may  be  produced 
temporarily  by  painting  any 
one  of  the  canals  with 
cocaine  so  as  to  paralyse 
its  nerve-endings.  The  con- 
verse experiment  of  isolated 
stimulation  of  one  canal  has 
also  been  effected  by  Ewald. 
For  this  purpose  Ewald,  by 
means  of  a  dentist's  burr, 
opened  one  bony  canal  at 
two  spots.  By  the  hole 
furthest  away  from  the 
ampulla    he    introduced    an  ^,^^  .^^.^ 

amalgam    stopping,     so     as 

to  prevent  any  current  of  fluid  backwards  through  the  canal.  Over 
the  second  hole  he  fixed,  by  means  of  plaster  of  Paris,  a  tube  which 
was  connected  by  a  flexible  rubber  tube  with  a  rubber  ball.  By  this 
means,  while  the  bird  was  sitting  quietly  on  its  perch,  he  could 
suddenly  blow  upon  the  exposed  membranous  canal  without  dis- 
turbing the  bird  in  any  way.  By  the  air  pressure  thus  produced 
on  the  canal  a  stream  of  endolymph  was  caused  in  the  direction 
of  the  ampulla.  Every  time  this  was  done  he  found  that  the  animal 
moved  its  head  and  eyes  in  the  direction  of  the  current  and  always 
exactly  in  the  plane  of  the  canal  which  was  being  stimulated.  By 
this  means  proof  was  brought  of  the  correctness  of  the  theory  put 
forward  by  Breuer  and  Mach,  viz.  that  the  specific  stimulus  of  the 
nerve-endings  in  the  ampulla  is  afforded  by  the  current  of  the  endo- 
lymph in  the  semicircular  canals. 

Since  the  endolymph  is  a  fluid  with  inertia  it  will  not  immediately 
follow  a  rotational  movement  of  the  bony  walls  of  the  semicircular 
canals.  Thus  a  sudden  turning  of  the  head  from  left  to  right  will 
cause  movement  of  endolymph  towards,  and  therefore  increased 
pressure  on,  the  ampullary  nerve-endings  of  the  left  horizontal  canal, 


680  PHYSIOLOGY 

and  movement  of  endolymph  away  from,  and  therefore  diminished 
pressure  on,  the  corresponding  ampulla  of  the  right  side.  In  this 
way,  for  movement  in  any  given  plane,  the  two  corresponding  semi- 
circular canals  of  the  two  sides  are  synergic,  and  unite  in  sending 
impulses  which  guide  the  equilibrating  centres,  and  inform  us  of 
the  position  of  our  head  in  space,  -i'  One  canal  can  be  affected  by 
and  transmit  the  sensation  of  rotation  abont  (me  axis  in  one  direction 
only  ;  and  for  complete  perception  of  rotation  in  any  direction  about 
any  axis  six  semicircular  canals  are  required  in  three  pairs,  each 
pair  having  its  two  canals  parallel  (in  the  same  plane),  and  with 
their  ampullae  turned  opposite  ways.  Each  pair  would  thus  be 
sensitive  to  any  rotation  about  a  line  at  right  angles  to  its  plane 
or  planes,  the  one  canal  being  influenced  by  rotation  m  the  one  direc- 
tion, the  other  by  rotation  in  the  opposite  direction  "  (Crum  Brown). 
These  reflex  movements  of  head  and  eyes  are  the  invariable  result 
of  movements  set  up  in  the  endolymph,  and  occur  equally  well  in 
the  absence  of  the  cerebral  hemispheres.  If  an  animal  or  man  be 
placed  on  a  turntable  and  rotated,  his  first  tendency  will  be  to  turn 
Jiis  head  and  eyes  m  the  opposite  direction  to  that  of  rotation.  If 
the  rotation  be  continued,  the  endolymph  gradually  takes  up  the 
movement  of  the  surroimding  parts  ot  the  head,  and  if  the  eyes  be 
closed,  no  movement  of  head  or  eyes  is  observed.  If  now  the  rotation 
be  stopped,  the  endolymph  will  tend  to  go  on  moving,  and  the  effect 
will  be  the  same  as  if  a  movement  of  rotation  were  suddenly  begun 
in  the  opposite  direction.  Head  and  eyes  will  now  be  turned,  without 
any  volimtary  impulse,  in  the  direction  of  the  previous  rotation,  and 
in  consciousness  there  will  be  an  actual  sensation  of  rotation  in  the 
opposite  direction.  This  sensation  is  in  opposition  to  the  sensations 
derived  from  other  parts,  and  hence  the  feeling  of  giddiness  and  the 
actual  disorders  of  equihbrium  which  are  its  concomitants. 

That  this  feehng  of  giddiness  on  rotation  is  due  to  impulses  started 
in  the  semicircular  canals  is  shown  by  the  fact  that,  in  a  large  number 
of  deaf-mutes  where  these  organs  are  imperfectly  developed,  it  is 
impossible  to  produce  giddiness  and  the  associated  eye  movements 
by  passive  rotation. 

THE  FUNCTION  OF  THE  OTOLITHS 
The  semicircular  canals  are,  as  we  have  seen,  a  higher  develop- 
ment of  the  otolith  organ.  The  primitive  part  of  this  organ  is  repre- 
sented by  the  maculae  in  the  utricle  and  saccule.  It  is  to  these  organs 
that  we  must  ascribe  our  powers  of  appreciating  the  static  position 
of  the  head,  as  well  as,  to  a  slight  degree,  movements,  not  of  rotation, 
but  in  one  plane  forwards  or  backwards. 

A  consideration  of  the  structure  of  the  otolith  organ  shows  at 


THE  LABYRINTHINE  SENSATIONS  681 

once  that  the  incidence  of  the  weight  of  the  otohths  on  the  hairs  of 
the  macula  will  vary  according  to  the  position  of  the  head.  Thus  in 
the  diagram  (Fig.  201,  p.  450)  in  a  (normal  position)  the  chief  weight 
of  the  otolith  falls  on  the  hairs  from  b  to  c,  whereas,  when  the  head 
has  been  rotated  round  a  right  angle  so  that  the  man,  for  instance, 
is  lying  oil  liis  right  side,  the  chief  weight  of  the  otoliths  will  fall  on 
the  hairs  from  c  to  d.  The  nerve-endings  stimulated  by  the  weight 
of  the  otoliths  will  therefore  vary  according  to  the  position  of  the 
head.  The  cerebellum  and  its  associated  structures  represent  a 
mechanism  for  the  regulation  of  the  movements  of  the  trunk  as 
a  whole  and  the  position  of  its  centre  of  gravity  in  relation  to  the 
position  of  the  head. 

The  beginning  and  ending  of  all  movements  of  the  head,  or  any 
change  in  the  rate  at  which  it  is  moving,  must  cause  a  momentary 
alteration  of  the  incidence  of  pressure  of  the  otohths  on  the  sensory 
hairs.  Any  translatory  movements  of  the  head  must  therefore 
excite  a  set  of  nerve  fibres  which  will  be  constant  for  each  direction. 
We  are  therefore  justified  in  ascribing  to  these  organs  the  functions 
possessed  by  the  otolith  organ  throughout  the  animal  kingdom, 
viz.  the  transmission  of  impulses  to  the  central  nervous  system 
which  are  aroused  by  the  position  or  movements  of  the  head,  and, 
hke  the  sensations  from  the  muscles,  regulate  and  govern  any  motor 
reaction  to  a  sensory  stimulus.  Of  these  afferent  impulses  a  certain 
proportion  will  arrive  at  the  cerebral  cortex,  and  in  consciousness 
will  inform  us  of  our  position  in  space  and  of  the  direction  and  extent 
of  any  movement,  active  or  passive,  of  the  head. 


L 


BOOK  III 
THE  MECHANISMS  OF  NUTRITION 


CHAPTER  IX 

THE  EXCHANGES   OF  MATTER  AND   ENERGY 
IN  THE   BODY 

GENERAL   METABOLISM 

All  the  energy  which  leaves  the  body  as  heat  or  work  is  derived 
from  processes  of  oxidation,  the  carbon,  hydrogen,  nitrogen,  and 
sulphur  of  the  food-stuffs  uniting  with  oxygen  in  the  body  and  being 
eliminated  in  the  form  of  carbon  dioxide,  water,  urea  and  other 
substances,  and  sulphates.  In  a  starving  animal  this  discharge  of 
energy  must  be  associated  with  a  loss  of  body  substance.  The 
necessity  for  taking  food  is  determined  by  the  need  of  replacing 
this  loss.  The  food-stuffs  cannot,  like  the  coal  or  fuel  of  a  steam- 
engine,  be  utilised  directly  as  a  source  of  energy,  but  must  be 
built  up  to  a  greater  or  less  degree  into  the  structure  of  the  living 
protoplasm.  The  total  amount  of  living  material  in  the  body, 
though  maintained  fairly  constant  in  the  adult  animal,  may  yet 
undergo  alterations  under  varying  conditions,  and  these  alterations 
are  naturally  more  marked  in  the  growing  animal.  We  have  in  this 
chapter  to  inquire  into  : 

(1)  The  nature  and  amount  of  the  substances  which  may  serve  as 
food-stuffs  and  are  necessary  for  maintaining  the  weight  of  the  body 
constant  or  providing  for  its  growth  ; 

(2)  The  relation  between  the  total  amount  of  material  taken 
up  by  the  body  and  the  total  amount  given  out ; 

(3)  The  variations  in  the  total  chemical  exchanges  determined 
by  variations  in  the  output  of  energy  by  the  body  ;  and 

(4)  The  significance  of  the  various  classes  of  food-stuffs  as  sources 
of  energy  and  in  the  replacing  of  tissue  waste. 

We  have  therefore  to  make  balance-sheets  of  two  kinds,  namely  : 
(I)  an  accurate  comparison  of  the  ingesta  (food  and  oxygen)  and 
the  egesta  (carbon  dioxide,  water,  urea,  &c.) ;  and  (2)  one  showing 
the  amount  of  potential  energy  introduced  into  the  body  com})ared 
with  the  amount  of  energy  set  free  in  the  body. 


686 


SECTION  I 

METHODS  EMPLOYED  IN  DETERMINING  THE 
TOTAL  EXCHANGES  OF  THE  BODY 

The  determination  of  the  material  exchanges  of  the  body  involves 
an  accurate  comparison  of  its  income  and  output.  The  income 
consists  of  the  food-stuffs  and  oxygen.  The  food-stufEs  may  be 
divided  into  two  classes,  namely,  (1)  the  organic  food-stuffs,  which 
on  oxidation  may  serve  as  sources  of  energy,  and  (2)  the  inorganic 
food-stufEs,  such  as  salts  and  water. 

The  latter  class  neither  add  to  nor  subtract  from  the  total  energy 
of  the  organism,  but  their  presence  is  a  necessary  condition  of  all 
vital  processes,  and  as  they  are  contained  in  the  various  excreta 
a  corresponding  amount  must  be  present  in  the  food  in  order  to  make 
good  this  loss. 

In  spite  of  the  bewildering  complexity  of  the  nature  of  the  foods 
taken  by  man,  their  essential  constituents  can  always  be  confined 
to  the  three  classes,  proteins,  fats,  and  carbohydrates,  and  any 
analysis  of  the  food  must  give  the  relative  amounts  present  of  these 
three  classes  of  substances.  The  approximate  analysis  of  the 
food-stuffs  presents  little  diflS.culty.  The  nitrogen  is  determined 
by  Kjeldahl's  method.  The  figure  thus  obtained  is  multiphed  by 
the  factor  6-25,  and  the  resulting  figure  is  taken  to  represent  the  total 
protein  in  the  food.  Of  course  such  a  valuation  may  give  too  high 
a  value  when  the  food-stuff  is  one  that  is  rich  in  nitrogenous  extrac- 
tives. The  total  fat  is  determined  by  extracting  the  food  in  a 
Soxhlet  apparatus  with  ether.  It  is  advisable  to  precede  this 
extraction  by  an  extraction  with  boiUng  alcohol.  The  total  ethereal 
and  alcohoUc  extract  obtained  is  reckoned  as  fat.  The  amount  of 
water  is  determined  by  drying  the  food-stuff  at  110°  C,  and  the 
amount  of  inorganic  constituents  by  ashing  the  dried  remainder. 
Carbohydrates  may  be  determined  directly  by  boihng  the  food 
with  dilute  acids  in  order  to  convert  all  its  disaccharides  and 
polysaccharides  into  hexoses,  which  are  then  reckoned  as  glucose, 
and  estimated  by  their  copper-reducing  power.  In  most  cases, 
however,  the  total  protein,  fat,  and  ash  are  subtracted  from  the  dried 
weight  of  the  food  and  the  remainder  is  taken  as  carbohydrate. 

Although  the  methods  for  the  analysis  of  food-stuffs  are  by  no 

686 


THE  TOTAL  EXCHANGES  OF  THE  BODY  087 

means  difHcnilt,  the  total  analysis  of  the  food  during  a  metabolism 
experiment  may  become  extremely  tedious  on  account  of  the  very 
large  number  of  analyses  which  have  to  be  performed.  The  labour 
is  lightened  by  the  fact  that  nearly  all  the  ordinary  food-stuffs  have 
bjeen  subjected  to  analysis  and  their  average  composition  pubhshed 
by  the  Agricultural  Board  of  the  United  States.  Since,  however,  the 
foods  vary  in  composition,  especially  in  water  content,  from  time 
to  time,  a  calculation  of  the  total  income  of  proteins,  fats,  and 
carbohydrates  from  data  given  by  workers  in  other  lands  must 
present  a  considerable  margin  of  error.  In  order  to  attain  greater 
accuracy  some  observers  have  made  a  complete  food  in  the  form 
of  biscuits  or  of  preserve  which  is  prepared  in  large  quantities  at 
the  beginning  of  the  experiment  and  used  as  the  sole  food 
throughout  the  experiment.  Pfiiiger,  for  instance,  converted 
the  horse-flesh,  with  which  he  desired  to  feed  his  dogs  in  a  meta- 
bolism experiment,  into  sausage  meat  which  was  sealed  up  in  cases 
and  sterilised.  The  sausage  meat  having  been  analysed  at  the 
beginning  of  the  experiment,  it  was  only  necessary  thereafter  to 
weigh  the  amount  eaten  by  the  dog  in  order  to  know  accurately 
the  total  amount  of  protein,  fat,  and  carbohydrate  ingested  by  the 
animal.  In  experiments  on  man  it  has  been  endeavoured  to  obtain 
the  same  result  by  limiting  the  food  to  a  few  articles  of  diet  which 
could  be  accurately  analysed  in  each  case.  The  monotony  of  such 
a  diet  tends  to  interfere  with  the  success  of  the  experiment,  since 
the  subject  of  the  experiment  loses  his  appetite  and  his  processes 
of  nutrition  are  not  normally  carried  out.  It  is  usually  possible 
to  steer  a  middle  course  between  the  two  extremes  of  too  much 
and  too  little  variation  of  diet,  and  so  to  obtain  values  for  the 
composition  of  the  ingesta  which  cannot  differ  very  largely  from 
their  true  composition. 

The  material  output  of  the  body  consists  of  the  products  of  com- 
bustion of  the  food-stuffs,  which  are  turned  out  by  the  various  channels 
of  excretion,  namely,  the  kidneys,  the  alimentary  canal,  the  lungs, 
and  the  skin.  These  excreta  must  therefore  be  collected  and  analysed. 
In  addition  to  the  main  sources  of  excretion,  small  quantities  of 
material  are  lost  by  the  shedding  of  the  cuticle,  by  the  growth 
and  cutting  of  the  hair  and  nails,  and  so  on.  In  most  cases 
the  losses  in  this  way  are  so  small  that  they  may  be  disregarded. 
The  nitrogen  of  the  food-stuffs  and  that  derived  from  the  dis- 
integration of  the  tissues  of  the  body  is  excreted  ahnost  exclusively 
in  the  urine,  a  small  amount  being  thrown  out  by  the  alimentary 
canal.  The  total  nitrogen  nuist  be  therefore  determined  both  in  the 
faeces  and  in  the  urine.  The  nitrogen  in  the  faeces  ia  derived  from 
two  sources.     Part  represents  those  nitrogenous  constituents  of  the 


088 


PHYSIOLOGY 


tissues  whicli  have  resisted  the  digestive  processes  of  the  ahmentary 
canal.  There  is  in  addition  a  certain  amount  derived  from  the 
intestine  itself.  During  complete  starvation  faecal  masses  are  formed 
in  the  intestine,  and  it  has  been  calculated  that  in  a  normal  individual 
about  one  gramme  of  nitrogen  a  day  is  excreted  by  the  mucous 
membrane  of  the  gut  and  contributes  to  the  formation  of  the  faeces. 
It  is  usual  therefore  to  regard  one  gramme  of  the  nitrogen  of  the 
fgeces  as  belonging  to  the  output  of  the  body  and  representing  the 
result  of  nitrogenous  metabolism,  while  the  balance  is  taken  as 
belonging  to  undigested  food-stuffs,  and  is  subtracted  from  the  total 
nitrogen  of  the  latter  in  reckoning  the  real  income  of  the  body.  A 
small  amount  of  nitrogen  is  also  lost  by  sweat,  but  this  can  be  dis- 
regarded unless  the  sweating  is  profuse,  when  the  loss  of  nitrogen 
by  this  channel  may  rise  to  as  much  as  -4  per  cent,  of  the  total  nitro- 
genous output  of  the  body.  Although  a  trace  of  ammonia  has  been 
described  as  occurring  in  the  expired  air,  the  amount  is  so  minute 
that  any  loss  of  nitrogen  by  the  lungs  can  be  neglected.  That  the 
loss  both  by  lungs  and  skin  under  ordinary  circumstances  can  be 
disregarded  is  shown  by  the  fact  that  it  is  possible  to  account  directly 
for  the  whole  nitrogen  of  the  body  by  a  comparison  of  the  composition 
of  food  with  that  in  the  urine  and  faeces.  If,  for  instance,  an  animal 
is  kept  on  a  sufficient  diet  which  contains  a  perfectly  regular  amount 
of  nitrogen,  after  a  few  days  a  condition  known  as  nitrogenous  equili- 
brium is  set  up,  i.e.  the  total  nitrogen  of  faeces  and  urine  is  exactly 
equal  to  the  total  nitrogen  of  the  food.  The  same  thing  applies 
to  the  sulphur,  as  is  shown  in  the  following  Table  (quoted  by 
Tigerstedt) : 


Days  of 
experiment 

Nitrogen 
of  food 

Kitrogen 
excreted 

Per  cent, 
difference 

Sulpliur 
ingested 

Sulphur 
excreted 

1-7 

8-17 

154-81 
213-72 

153-02 
213-2G 

-0-51 
-0-21 

12-77 

12-79 

In  order  to  express  the  nitrogenous  metabolism  in  terms  of 
protein,  we  use  the  factor  employed  in  estimating  the  amount  of 
protein  in  the  food,  i.e.  we  multiply  the  total  nitrogen  of  the  excreta 
by  625.  This  will  give  the  total  protein  which  has  been  broken 
down  during  the  period  of  the  experiment.  Much  more  important 
from  the  energy  standpoint  is  the  determination  of  the  total  processes 
of  oxidation  of  the  body,  information  on  which  is  given  by  a  com- 
parison of  the  oxygen  intake  with  the  output  of  carbon, dioxide  and 
water.  The  estimation  of  these  substances  presents  much  greater 
difficulties  than  the  investigation  of  the  nitrogenous  exchange  and 


THE  TOTAL  EXCHANGES  OF  THE  BODY  689 

involves  the  use  of  some  form  of  respiration  apparatus.  The  fol- 
lowing are  the  chief  methods  which  have  been  employed  for  this 
purpose  : 

I.  THE  METHOD  OF  HALDANE.  This  method  is  extremely- 
convenient  when  dealing  with  the  gaseous  exchanges  of  small 
animals,  such  as  mice,  rats,  guinea-pigs,  or  rabbits.  The  animal 
is  placed  in  the  chamber  c,  which  may  be  simply  a  wide-mouthed 
bottle  (Fig.  314).  This  chamber  is  supplied  with  a  thermometer, 
and  can  be  kept  at  any  desired  temperature  by  immersion  either 
in  warm  or  cold  water.  On  the  inlet  side  of  the  bottle  is  a 
series  of  tubes  or  bottles,  some  of  which  contain  sulphuric  acid 
and  pumice-stone,  while  the  others  contain  soda  lime.  On  the 
outlet  side  of  the  vessel  is  a  corresponding  series  of  vessels  for  the 


Soda  Lime      HjSO^ 


Fig.  314.     Haldane-Pembrey  respiration  apparatus. 
c,  chamber  for  animal  ;   M,  gas  meter. 

absorption  of  water  and  of  carbon  dioxide.  On  the  further  side 
of  these  vessels  is  a  gas  meter.  During  an  experiment  air  is  sucked 
through  the  whole  apparatus  by  means  of  an  aspirator  or  a  water 
pump,  the  amount  of  air  passing  through  the  apparatus  being  measured 
by  the  meter.  The  animal  is  thus  supplied  with  pure  air  freed  from 
water  vapour  and  from  carbon  dioxide.  Any  water  or  carbon  dioxide 
produced  by  the  animal  is  absorbed  by  the  vessels  interposed  in  the 
course  of  the  outgoing  air.  These  vessels  are  weighed  at  the  beginning 
of  the  experiment  and  at  the  end,  and  the  difference  in  weights  will 
therefore  give  the  amounts  of  carbon  dioxide  and  water  which  have 
been  discharged  by  the  animal. 

The  intake  of  oxygen  by  the  animal  is  determined  indirectly. 
.Since  it  gives  off  only  carbon  dioxide  and  water,  and  absorbs  only 
oxygen  during  its  stay  in  the  chamber,  the  loss  of  weight  of  the 
animal  during  its  stay  in  the  chamber,  subtracted  from  the  total 
amount  of  carbon  dioxide  plus  water  it  gives  off.  will  represent  the 
amount  of  oxygen  absorbed. 

The  advantage  of  this  apparatus  is  that  it  can  be  fitted  up  in 
any  laboratory,  and  is  accurate  for  the  purposes  to  which  it  is  applied. 
It  is  not,  however,  appropriate  for  long-continued  experiments  or 
for  experiments  on  larger  animals  or  on  man  himself.     Most  of  the 

44 


690  PHYSIOLOGY 

data  with  regard  to  the  respiratory  exchange  under  various  circum- 
stances have  therefore  been  obtained  by  one  of  the  three  following 
methods  : 

II.  THE  METHOD  OF  REGNAULT  AND  REISET.  The  prin- 
ciple of  this  method  consists  in  placing  the  animal  that  is  to  be  the 
subject  of  investigation  in  a  closed  chamber  containing  a  given 
volume  of  air.  The  carbon  dioxide  produced  by  the  animal 
is  absorbed  by  means  of  caustic  alkali,  and  the  oxygen  consumed 
by  the  animal  is  made  good  by  allowing   oxygen  to  flow  into  the 

chamber  from  a  gasometer. 
The  inflow  of  oxygen  is 
regulated  so  as  to  keep 
the  pressure  of  air  in 
the  chamber  constant.  At 
the  end  of  the  experi- 
ment the  alkali  is  titrated 
and  the  amount  of  carbon 
dioxide   absorbed   thus 

^eso»BED  ,  -«««««  p  determined.    The  air  in  the 

-'     ' '     ' '  chamber   is   also   analysed 


^W 


I  tCAKBOH  DiatlOt  > ' 

ABSORBED 


Fig.  315.     Air  circuit  in   Bencdicf.s    rcspii'ation       g^   ^s  to   be  certain  that  it 
apporat\is. 

contams  an  excess  neither 

of  carbon  dioxide  nor  of  oxygen.      The  amount  of  oxygen  absorbed 

by  the  animal  is  known  already,  the  oxygen  which  has  been  allowed 

to  flow  in  having  been  measured. 

A  modification  of  this  method  has  been  devised   by  Benedict 

and  is  especially  applicable  to  cUnical   purposes.     In   this   method 

the    individual    who    is    the    subject    of    the    experiment    breathes 

through    a    nose-piece    into    a    wide    metal    tube,   the   mouth   being 

kept  closed.     The  metal  tube  forms  part  of  a  closed  system  through 

which   a  current   of  air  is   maintained   by   means   of  a   pump.      In 

the    course    of    the    current    of    air    are    interposed   vessels   for  the 

absorption    of   carbon    dioxide    and    of    water,   and   the   volume    of 

gas   in    the    system   is    maintained    constant    by   admitting    oxygen 

to    it    in    proportion    as    the    oxygen    of    the    system    is    used    up 

in  respiration.     In  Fig.  315  is  given  a  diagrammatic  scheme  of  the 

air  circuit,  and  in  Fig.  316  a  diagram   of   the   arrangement  of  the 

whole  respiration  apparatus,  showing  the  nose-piece  for  breathing, 

the  tension  equaliser,  the  air-purifying  apparatus,  and  the  oxygen 

cylinder.     The   tension  equahser,  A,  is  attached  to  the  ventilating 

pipe  near  the  point  of  entrance  of  the  air  into  the  lungs.     It  consists 

of  a  j)an  with  a  rubber  diaphragm  (which  may  be  conveniently  made 

from  a  lady's  bathing-cap).      As   the    air   is  drawn    into   the   lungs 

the   rubber   diaphragm   sinks,  to  rise   again    with  i^xpiration.      The 


THE  TOTAL  EXCHANGES  OF  THE  BODY 


cm 


respiratory  movements  can  thus  proceed  without  altering  appreciably 
the  pressure  within  the  closed  system  of  tubes.  By  the  admission  of 
oxygen  the  supply  of  oxygen  is  adjusted  so  as  to  keep  the  bag  from 
becoming  either  too  much  distended  or  too  much  flattened.  As 
the  air  leaves  the  lungs  and  passes  into  the  constantly  moving  current 
of  air,  it  is  carried  along  by  the  pump  and  flows  through  two  Wolff's 
bottles  containing  strong  sulphuric  acid  and  pumice  for  the  removal 
of  water  vapour.    It  then  passes 

through  a  brass  cyhnder,  c,  filled  "^U     ^rj 

with  soda  lime  for  the  absorp- 
tion of  carbon  dioxide.  From 
here  it  passes  again  through 
sulphuric  acid  in  a  Kipp  gener- 
ator for  the  absorption  of  water 
given  off  by  the  soda  lime. 
Since  the  air  so  deprived  of 
moisture  would  be  uncomfort- 
able to  breathe,  it  is  then 
carried  through  another  Kipp 
generator  containing  water  with 
a  trace  of  sodium  carbonate  for 
the  neutralisation  of  any  acid 
fumes  which  may  be  given  off 
by  the  sulphuric  acid.  It  then 
passes  back  to  the  tube  from 
which  the  subject  is  breathing. 
In  this  way  it  is  possible  to 
determine  very  accurately  the 
amount  of  oxygen  used  up  and 
the  amount  of  carbon  dioxide 
given  off   in  the  course  of   an 

experiment  lasting  one  to  three  hours  or  longer.  The  oxygen  con- 
sumption is  measured  by  weighing  the  cyhnder  of  this  gas,  chosen 
small  for  this  purpose,  before  and  after  the  experiment. 

III.  PETTENKOFER'S  METHOD.  In  the  apparatus  designed  by 
Pettenkofer  the  animal  or  man  was  placed  in  a  chamber  through 
which  a  constant  current  of  fresh  air  was  passed.  The  amount  of  air 
passing  through  the  chamber  was  measured  by  means  of  a  meter. 
Throughout  the  experiment  continuous  samples  both  of  the  air  enter- 
ing the  chamber  and  of  the  air  leaving  the  chamber  were  taken.  The 
analyses  of  these  samples  served  to  show  the  composition  of  the  whole 
air  entering  and  leaving  the  chamber,  and  therefore  the  changes  in 
the  air  caused  by  the  presence  of  the  animal.  The  advantage  of  this 
apparatus  is  that  an  adequate  ventilation  can  be  kept  up,  and  the 


Fig.  316.     Arrangement  of   apparatus  in 
Benedict's  method  for  determination  of 
respiratory  exchange. 
N,  tubes  inserted  into  nostrils  of  patient  ; 
A,  tension  equaliser;    c,  cylinder  contain- 
ing soda  lime  for  absorbing  CO.,. 


692  PHYSIOLOGY 

apparatus  can  be  built  of  any  size.  In  the  apparatus  of  Tigerstedt 
built  on  this  plan  the  chamber  had  a  capacity  of  100-6  cubic  metres, 
and  was,  in  fact,  a  small  room.  A  similar  respiratory  apparatus  has 
been  built  by  Atwater. 

IV,  ZUNTZ  AND  GEPPERT'S  METHODS.  For  many  purposes 
the  methods  devised  by  Zuntz  and  Geppert  present  many  advan- 
tages, especially  when  it  is  desired  to  take  the  respiratory  ex- 
changes in  man  or  any  animal  during  a  limited  period  of  time.  The 
subject  of  the  experiment  has  his  nostrils  clamped  and  breathes 
into  and  out  of  a  face-piece.  This  face-piece  is  provided  with 
valves  either  of  aluminium  or  of  animal  membrane,  which  serve 
to  separate  the  in-going  from  the  out-going  current  of  air.  In 
the  course  of  the  out-going  current  is  placed  a  very  delicate  gas 
meter  which  presents  practically  no  resistance  to  the  air  current. 
A  branch  from  the  efflux  tube  passes  to  a  gas  analysis  apparatus. 
By  an  ingenious  method  it  is  arranged  that  an  aliquot  part  of  the 
whole  of  the  out-going  air  is  drawn  off  into  this  apparatus,  so  that 
the  experiment  can  be  interrupted  at  any  time,  and  the  analysis 
of  this  sample  will  give  the  average  composition  of  the  expired  air, 
and  therefore,  on  multiplication  by  the  total  gas  passing  through 
the  gas  meter,  the  total  output  of  carbon  dioxide  during  the  course 
of  the  observation.  One  advantage  of  this  method  is  that  the 
apparatus  is  portable,  and  can  be  applied  to  the  investigation  of  the 
respiratory  exchanges  of  patients  in  hospitals  or  of  man  or  animals 
while  they  are  walking  about.  It  has  been  used,  for  instance,  by 
Zuntz  and  his  pupils  in  an  interesting  series  of  researches  on  the 
gaseous  metabolism  of  men  at  high  altitudes. 

By  means  of  one  or  more  of  these  methods  we  may  arrive  at  a 
correct  idea  of  the  total  income  and  output  of  an  individual  for  periods 
of  many  days.  The  following  details  by  Tigerstedt  may  serve  as  an 
example  of  the  results  obtained  in  such  an  experiment.  The  experi- 
ment lasted  two  days.  The  subject  was  a  man  of  twenty-six  years 
of  age,  weighing  about  65  kilos,  who  had  previously  taken  no  food 
for  five  days.  The  Tables  on  p.  693  represent  his  material  income  and 
output. 

As  we  should  expect  in  a  man  who  had  fasted  five  days,  this  balance- 
sheet  shows  a  marked  retention  of  the  food  taken  in,  i.e.  a  marked 
excess  of  income  over  output.  Thus  of  the  nitrogen  ingested,  13  grm., 
which  is  equivalent  to  81-3  grm.  of  protein,  was  retained  ;  of  the 
carbon,  302  grm.  was  retained.  Of  this  302  grm.,  42-7  grm.  would 
be  contained  in  the  81*3  grm.  of  protein,  so  that  the  rest  of  the  carbon, 
namely,  259*6  grm.,  was  probably  laid  down  in  the  form  of  fat. 
This  would  correspond  to  339  grm.  of  fat.  Of  the  salts  contained 
in  the  ash  of  the  food,  25  grm.  were  retained  in   the   body.     The 


THE  TOTAL  EXCHANGES  OF  THE  BODY 


G93 


carbon  and  nitrogen  reappearing  in  the  excreta  serve  as  an  index 
of  the  amount  of  metabolism  of  the  food-stuffs  which  had  occurred 
during  the  two  days.  In  order  to  supply  the  energy  requirements 
of  the  body  during  the  time  of  the  experiment,  498  grm.  of  carbo- 
hydrate, 59  grm.  of  alcohol,  and  138  grm.  of  fat  had  been  completely 

Total  Income 


Food 

n 

N. 

c. 

2 

a 
2 

Fat 

Ash 

2 
o 

o 

Bread       . 
Butter      . 
Cheese 
Salt  meat 
Milk 
Broth 
Beer 

Beef  steak 
Potatoes  . 
Water 

373 

388 

116 

26 

2313 
658 

1413 
700 
452 

2335 

7-3 

0-4 

4-3 

11 

11-3 

11-8 

1-2 

20-6 

0-9 

36 

37 

56 

16 

2047 

580 

1273 

533 

359 

2335 

337 
351 

60 

10 

266 

78 

77 

167 

93 

46 

3 
27 

9 
71 
74 

S 
129 

6 

4 

337 

35 

85 

33 

1 

278 
4 

95 

67 

82 

9 
7 
5 
2 

16 
9 
3 

7 
5 

59 

Totals 

8773 

59-3 

831-6 

7275 

1439 

371 

497 

525 

61 

59 

Total  Output 


Total 
amouDt 

N. 

C. 

Water 

Solids 

Protein 

Fat 

Carbo- 
hydrate 

Asli 

Respiration . 
Urine 

Faeces     . 

2701 

2564 

455 

41-5 

4-8 

453-C 
32-5 
43-8 

2248 

2490 

363 

91-6 

30 

20 

27 

21 
15 

Totals     . 

5720 

46-3 

529-3 

5101 

91-6 

30 

20 

27 

36 

oxidised.  The  amount  of  protein  used  up  during  this  time  can  be 
obtained  by  multiplying  the  nitrogen  of  the  urine  plus  1  grm.  of 
nitrogen  of  the  faeces  by  the  factor  6-25,  and  is  found  to  amount  to 
271-9  grm. 

THE  ENERGY  BALANCE-SHEET  OF  THE  BODY 
The  energy  income  of  the  body  is  measured  by  the  potential 
energy  of  the  food-stuffs,  i.e.  the  amount  of  energy  which  can  be 
evolved,  either  as  heat,  work,  or  in  any  other  form,  by  the  oxida- 
tion of  the  food-stuffs  to  the  end-products  which  occur  in  the 
body.       Since    it    is   convenient    to    have    a    uniform     method    of 


694 


PHYSIOLOGY 


expressing  the  total  potential  energy  of  a  food-stuff,  we  generally 
express  it  in  calories,  and  speak  of  the  heat-value  of  a  food-stufT. 
The  heat-value  of  any  given  food  is  the  amount  of  large  calories  * 
which  it  evolves  on  complete  combustion  with  oxygen,  and  is  deter- 
mined by  burning  a  weighed  quantity  of  the  dried  food-stuff  in 
oxygen  in  the  bomb  calorimeter.  The  following  heat-values  have 
been  obtained  for  different  food-stuffs  : 


Substance 

Heat  value 

Lean  meat 

.     5-656  (or  5-345  Rubner) 

Lard 

.     9-423 

Butter 

.     9-231 

Grape  sugar 

.     3-692 

Cane  sugar. 

.     4-116 

Starch 

.     4-191 

In  the  case  of  some  food -stuffs  it  is  necessary  to  draw  a  distinction 
between  the  absolute  heat-value  and  the  physiological  heat-value. 
Since  carbohydrates  and  fats  undergo  complete  oxidation  in  the 
body  to  carbonic  acid  and  water,  their  physiological  heat-values,  i.e. 
the  values  of  these  food-stuffs  to  the  organism,  are  identical  with 
their  absolute  heat-values.  Proteins,  however,  do  not  undergo  com- 
plete oxidation.  When  they  are  oxidised  in  the  bomb  calorimeter 
the  nitrogen  is  set  free  in  a  gaseous  form.  In  the  animal  body 
no  nitrogen  is  eliminated  in  the  gaseous  form,  the  whole  of  it 
being  excreted  as  urea  and  allied  substances  still  endowed  with 
a  considerable  store  of  potential  energy,  which  can  be  set  free 
when  their  oxidation  is  completed  in  a  calorimeter.  In  order  to 
determine  the  physiological  heat-value  of  protein  we  must  subtract 
from  its  absolute  heat-value  the  heat-value  of  the  excretory  products 
in  .  the  form  of  which  it  leaves  the  body.  The  physiological  heat 
value  of  proteins  has  been  determined  by  Rubner  in  the  following 
way  :  A  dog  was  fed  with  the  same  protein  which  had  served  for 
the  determination  of  the  absolute  heat- value.  While  the  dog  was 
receiving  this  food  its  urine  was  collected,  dried,  and  its  heat- value  deter- 
mined by  combustion  in  the  calorimeter.  It  was  found  that  for  each 
gramme  of  protein  which  had  undergone  disintegi-ation  in  the  body 
an  amount  of  urine  was  passed  corresponding  to  a.  heat-value  of 
1-0945  calories.  The  heat- value  of  the  faeces  formed  under  the  same 
diet  was  0-1854  calorie  for  each  gramme  of  protein.  Rubner 
further  reckoned  that  a  certain  amount  of  heat  would  be  required 
for  the  solution  of  the  proteins  and  of  the  urea,  and  reckoned  this 
at  0-05  calorie.     The  reduced  or  physiological  heat-value  of   protein 

*  A  calorie  is  the  amount  of  heat  necessary  to  raise  a  gramme  of  water  from 
0°  C.  tol°C.  A  large  calorie  is  the  heat  required  to  raise  a  kilogramme  of  water 
from  0°  C.  to  1°  C,  and  is  therefore  equal  to  1000  small  calories. 


THE  TOTAL  EXCHANGES  OF  THE  BODY  695 

is     therefore     equal     to     5-:}45  -  (1-0945  +  0-1854  +  <>05)  =  4-015 
calories. 

A  deteriniiiatioii  of  the  heat-values  of  the  various  food-stuffs 
shows  minute  differences  between  individual  members  of  the  same 
class.  Since  it  is  impossible  to  reckon  out  accurately  the  relative 
amounts  of  the  different  kinds  of  protein,  carbohydrate,  &c.,  contained 
in  each  diet,  Rubner  has  calculated  the  average  physiological  heat- 
values  of  the  three  classes  of  food-stuffs.  These  figures  have  been 
universally  adopted,  and  are  as  follows  : 

1  grm.  protein  =4-1  calories 

1  grm.  fat  =  9-3       „ 

1  grm.  carbohydrate  =  4-1       ,, 

Careful  experiments  have  shown  that  just  as  there  is  no  loss  of 
matter  in  the  body,  so  also  the  sum  of  the  energies  put  out  by  the 
body  is  equal  to  the  sum  of  the  energy  obtained  by  the  oxidation 
of  the  tissues  and  of  the  food-stuffs  in  the  tody  during  the  same 
time.  In  an  earlier  chapter  I  have  quoted  the  results  of  an  experi- 
ment by  Rubner  on  a  dog,  which  demonstrated  this  equivalence,  as 
proving  the  important  fact  that  the  fundamental  doctrine  of  the 
Conservation  of  Energy  applies  to  the  organised  as  to  the  inanimate 
world.  Similar  results  have  been  arrived  at  by  Atwater  in  a  series 
of  experiments  with  a  special  calorimeter  on  man.  It  may  be  suffi- 
cient here  to  give  the  figures  from  one  such  experiment  : 


a 

b 

c 

d 

e 

f 

a 

h 

i 

Date 

Gals. 

Cals. 

Cals. 

Cals. 

Cals. 

Cals. 

Cals. 

Cals. 

c 

Dec.  9-10  . 

2519 

110 

142 

-85 

+    3 

2349 

2414 

-1-65 

+  2-8 

10-11  . 

2519 

110 

133 

-25 

-44 

2345 

2386 

-f-41 

-Hl-7 

11-12  . 

2519 

110 

132 

-21 

-93 

2391 

2413 

-(-22 

-fO-9 

12-13  . 

2519 

110 

133 

-14 

—  O'i 

2345 

2375 

+  30 

-fl-3 

Total  4  days 

10076 

440 

540 

-145 

-189 

9430 

9588 

4-158 

Average      | 

one  day    I 

2519 

110 

135 

-36 

-47 

2357 

2397 

-1-40 

+  1-7 

_ 

,  ^ 

.  — . 

,  ^ 

'^-j 

^  — 

o 

"2 

'o 

"o 

c  — 

8- 

-t-.2 
^  9 

si 

o 

a 

o 

S 

S.S 

O.S 

°5 

g« 

it 

3 

1 

a 

o  to 

9  '5 

•a 

o 

Hi  _ 

m  - 
11 

3 
8 

p 

s 

=  IT 

■Z3  o    : 

■3  -a  u 

n 

c 

E 

o  c 

o 

o 

s"=  s 

2  c^ 

a.2f 

3  o  .2 

•S 

-i. 

■^  1  ^ 

p 

ll 

Z.    3 

Estin 
rial 
a     ( 

rt 

—    CM 

<a  ^_  •  ■ 

696 


PHYSIOLOGY 


If  we  take  into  account  the  great  difficulties  of  such  an  experi- 
ment, we  cannot  but  be  impressed  with  the  closeness  of  agreement 
between  the  total  output  of  energy  reckoned  as  heat  and  measured  by 
the  warming  of  a  given  volume  of  water  and  the  total  income  of  energy 
as  estimated  from  the  chemical  reactions  involved  in  the  metabolic 
changes  which  had  taken  place  during  four  days  of  the  experiment. 
The  important  result  which  comes  out  in  such  experiments  is  that 
the  food-stuffs  produce  the  same  amount  of  energy  when  oxidised 
in  the  body  as  Avhen  burnt  to  the  same  end-products  outside  the 


Double 
Window 


i 

Calorimeter 
Chamber. 


I 


kC 


^ 


Air  <  Water  +  COj;  deficient  in  Oxygen 


i 


^^a^g^j^?^^^?^^;'?^^;;^^^^ 


/? 


I      CO^       I  I    Water     I 

-■removed  ' '  removed 


by 


[Soda-Lime^  H 


Air 
Pump. 


Air  minus  CO,  and  Wa 


H;S04.  I  \ 

ter,  deficient  in  Oxygen.     >,^^  |        » 


Ony^en  enters.' 
Fig.  317.     Diagram  to  show  the  principle  of  the  Atwater-Benedict  calorimeter. 
(After  Halliburton.) 

body,  so  that  it  becomes  easy  in  any  given  research  to  sum  accurately 
the  energy  income  of  the  body. 

The  Atwater  calorimeter  has  been  improved  to  such  an  extent 
by  Benedict  and  his  fellow  workers  that  it  has  practically  replaced 
all  other  forms  for  physiological  purposes.  It  consists  of  a  room 
or  chamber  with  double  non-conducting  walls.  All  round  the  inner 
wall  of  the  room  are  fitted  coils  of  pipes  through  which  a  stream 
of  water  flows.  The  pipes  are  fitted  with  discs  so  as  to  take  up 
rapidly  heat  produced  in  the  room.  The  current  of  water  is  accurately 
adjusted  so  as  to  maintain  the  temperature  of  the  inner  wall  constant. 
As  the  inner  wall  and  outer  wall  are  kept  at  the  same  temperature, 
no  heat  is  lost  to  the  exterior,  the  whole  of  the  heat  produced  by 
the  animal  or  individual  in  the  chamber  being  communicated  to 
the  water  passing  through  the  chamber.  The  temperatures  of  the 
entering  and  leaving  water  are  taken  by  accurate  thermometers 
reading  to  a  hundredth  or  a  thousandth  of  a  degree  Centigrade. 
Knowing  the  amount  of  water  that  has  passed  through  in  a  given 
time  and  the  difference  in  temperature  during  the  same  time,  it  is 


THE  TOTAL  EXCHANGES  OF  THE  BODY  G97 

easy  to  calculate  the  amount  of  heat  given  off  by  the  animal  under 
investigation.  It  is  generally  convenient  to  maintain  a  constant 
difference  of  temperature  between  the  entering  and  leaving  water  by 
appropriate  adjustment  of  the  amount  of  water  passing  through  the 
apparatus.  The  equality  of  temperature  between  the  inner  and 
outer  casing  is  recorded  by  electric  thermo  couples,  any  difference  of 
temperature  being  at  once  compensated  by  electrically  warming 
the  cooler  part.  The  chamber  contains  a  bicycle  or  other  arrange- 
ment for  the  performance  of  mechanical  work.  It  is  adequately 
ventilated  by  a  current  of  air  passing  through  an  apparatus  similar 
to  that  of  Benedict,  described  on  p.  690.  It  is  thus  possible  to 
estimate  simultaneously  the  total  heat  production  of  an  indi\4dual 
as  well  as  the  respiratory  exchanges,  including  both  carbon  dioxide 
output  and  oxygen  intake.  The  general  principle  of  the  calorimeter 
is  shown  in  the  diagram  (Fig.  317).  The  calorimeter  is  also  supphed 
with  bed,  table,  chair,  &c.,  and  food  can  be  introduced  through  a 
double  window  so  that  an  experiment  may  be  continued  over  two 
or  three  days  on  one  and  the  same  individual 


SECTION  II 

THE  METABOLISM  DURING  STARVATION 

It  will  tend  to  simplify  our  task  if  we  deal  first  with  the  results 
of  the  experiments  which  have  been  made  on  the  inetaboHc  ex- 
changes of  animals  during  starvation,  i.e.  during  a  period  when  the 
whole  energy  involved  in  the  maintenance  of  the  movements  of 
respiration  and  circulation,  and  in  the  maintenance  of  the  body 
temperature,  &c.,  is  derived  from  the  animal's  own  tissues.  It  must 
be  remembered  that  the  tissues  of  an  animal  comprise  tw^o  distinct 
classes.  In  the  first  class  must  be  placed  the  living  machinery  of  the 
body,  generally  composed  of  proteins  or  their  near  allies.  In  the 
second  class  are  the  fatty  tissues  of  the  body,  which  form  no  part 
of  the  ordinary  machinery,  but  function  simply  as  a  storehouse 
of  material  which  can  be  utilised  for  the  production  of  energy.  In 
addition  to  the  store  of  fat  there  is,  in  a  well-fed  animal,  a  certain 
reserve  of  carbohydrate  in  the  form  of  glycogen,  deposited  in  the 
liver  and  muscles  of  the  body.  This  store  of  glycogen  is  drawn  upon 
to  a  large  extent  at  the  beginning  of  a  period  of  starvation.  The 
total  amount  of  glycogen  present  at  any  time  is  so  small  in  com- 
parison w^ith  the  possible  amount  of  fat  that  it  cannot  provide  the 
energy  necessary  for  the  prolonged  period  during  which  the  main- 
tenance of  life  is  possible  in  a  complete  state  of  inanition,  although 
it  plays  an  important  part  during  the  first  one  or  two  days  of  a  period 
of  starvation. 

Contrary  to  general  belief,  the  condition  of  an  animal  which 
is  completely  deprived  of  food  is  not  a  painful  one.  For  this 
statement  we  have  not  only  such  evidence  as  can  be  derived  from 
inspection  of  animals  placed  in  this  condition,  but  also  evidence 
derived  from  men  who  have  voluntarily  or  involuntarily  been 
deprived  of  food  for  considerable  periods.  Especially  instructive  in 
this  connection  are  the  cases  of  the  so-called  professional  '  fasting 
men,'  two  of  whom,  Succi  and  Cetti,  have  been  subjected  to  com- 
plete metabolic  investigation  during  the  period  of  their  starvation. 
During  the  first  day  or  two  there  is  a  craving  for  food  at  meal- times. 
This,  however,  passes  off,  and  during  the  later  portions  of  the  experi- 
ment even  the  desire  for  food  may  be  entirely  absent.  As  might 
be  expected,  the  restriction  of  food  is  followed  by  a  diminution  in 

698 


THE  METABOLISM  DURING  STARVATION  699 

the  amount  of  water  required  by  the  animal.  The  essential  char- 
acteristic of  the  state  of  inanition  is  an  ever-increasing  weakness, 
accompanied  by  a  strong  disincHnation  to  undertake  any  mental 
or  physical  exertion  whatsoever.  The  animal  passes  its  time  in  a 
state  of  sleep  or  of  semi-stupor.  In  the  case  of  Succi,  who  fasted 
for  thirty  days,  considerable  muscular  exertion  was  undertaken  on 
the  twelfth  and  on  the  twenty-third  day  of  starvation  without  any 
appreciable  ill-effects.  A  strong  effort  of  the  will  must  have  been 
necessary  in  his  case  to  overcome  the  autornatic  instinct  to  preserva- 
tion of  life  by  the  utmost  economy  in  the  expenditure  of  energy.  The 
pulse-rate  and  the  body  temperature  remain  nearly  normal  until  a 
few  days  before  death,  which  is  ushered  in  by  an  increase  in  the  somno- 
lent condition  of  the  animal  and  by  a  gradual  slowing  of  respiration 
and  fall  of  temperature.  The  urine  is  naturally  diminished  with 
diminution  in  the  output  of  urea  and  in  the  amount  of  water  consumed. 
Some  fa3ces  are  formed,  and  may  be  voided  during  or  at  the  close  of 
the  starvation  period.  In  Succi  their  amount  varied  from  9'5  to 
22  grm.  a  day  and  contained  from  0"3  to  TO  grm.  nitrogen.  On  micro- 
scopic examination  they  consisted  of  an  amorphous  material  enclosing 
a  number  of  crystals  of  fatty  acids. 

During  the  whole  of '  the  starvation  period  energy  is  being 
used  up  in  the  body  for  the  maintenance  of  its  temperature  and 
the  vital  movements  of  respiration  and  circulation.  Since  this 
energy  is  derived  from  the  destruction  and  oxidation  of  the  tissues 
of  the  body,  it  is  evident  that  starvation  must  be  associated  with 
a  constant  and  steady  loss  of  body  weight.  In  experiments  on 
man  the  daily  loss  of  weight  during  the  first  ten  days  amounts 
to  between  1  and  1-5  per  cent,  of  the  original  total  weight.  This 
loss  of  weight  does  not  affect  all  parts  of  the  body  alike.  It  might 
be  imagined  that,  since  the  loss  of  weight  is  determined  by  the  using 
up  of  the  tissues  of  the  body  for  the  production  of  energy,  those 
organs  which  are  most  active  should  show  also  the  greatest  loss  of 
weight.  The  very  reverse  of  this  is  the  case,  as  will  be  seen  from  the 
Table  on  p.  700. 

Those  organs  of  the  body  which  are  most  necessary  for  the  main- 
tenance of  life,  the  brain,  the  heart,  the  respiratory  muscles,  such 
as  the  diaphragm,  undergo  very  little  loss  of  weight.  Of  the  other 
tissues  the  fat,  which  is  a  mere  reserve  to  provide  for  such  contin- 
gencies, is  drawn  upon  first,  and  during  starvation  97  per  cent,  of  the 
total  fat  of  the  body  may  be  consumed.  The  nitrogen  needs  of  the 
body  during  starvation  seem  to  be  supplied  chiefly  at  the  expense 
of  the  muscles  and  glands,  which  waste  to  a  very  marked  degree. 
The  muscles  being  used  simply  as  reserve  material,  it  is  easy  to 
understand  the  condition  of  lethargy  and  muscular  inactivity  which 


700  PHYSIOLOGY 

characterises  the  state  of  inanition.  During  starvation  all  tissues 
of  the  body  undergo  a  process  of  autolysis  or  disintegration,  giving 
up  the  products  of  this  process  to  the  common  circulating  fluid. 
The  nutritional  demands  of  a  tissue  are  determined  by  its  activity. 
Hence  the  active  tissues  of  the  body  take  up  the  material  set  free 


Loss  IN 

Weight  of 

DiFFERENr  Organs  during  Starvation 

Fat-free  animal  contains  in  percentage 

Fresh  fat-free 

of  weight 

organ  loses  in 

Organ 

l)ercentage  weight 
duiing  a  24  days' 

Well-nourished 

Starvation 

fast 

Skeleton 

14-78 

21-50 

5 

Skin 

10-30 

11-29 

28 

Muscles 

53-77 

48-39 

42 

•  Brain  and  cord 

0-94 

1-11 

22 

Eyes 

0-11 

0-16 

3 

Heart 

0-54 

0-69 

16 

Blood      . 

7-14 

5-69 

48 

Spleen     . 

0-39 

0-26 

57 

Liver 

3-98 

3-05 

50 

Pancreas 

0-33 

0-19 

62 

Kidney 

0-66 

0-45 

55 

Genitals 

0-30 

0-23 

49 

,  Stomach  and  intestine 

5-81 

6-02 

32 

Lungs      .          .          .          .   j              0-89 

0-97 

29 

from  all  the  other  cells  of  the  body  and  so  maintain  their  weight 
at  the  expense  of  all  other  parts.  A  similar  predominance  of  the 
nutrition  of  active  over  inactive  tissues  is  to  be  observed  in  cases  of 
partial  starvation,  i.e.  where  the  deprivation  of  food  only  applies 
to  a  single  food  constituent.  Thus  Voit,  in  a  series  of  experiments, 
fed  pigeons  on  a  food  which,  while  normal  in  all  other  respects, 
contained  a  deficiency  of  calcium  salts.  On  killing  the  birds  after 
a  certain  length  of  time,  it  was  found  that  while  the  bones  used  in 
the  necessary  movements  of  the  animals  presented  a  normal  appear- 
ance, the  others,  such  as  the  sternum  and  skull,  showed  a  marked 
deficiency  of  lime  salts  and  had  undergone  a  process  of  rarefaction 
giving  rise  to  the  condition  known  by  pathologists  as  osteoporosis. 
Many  other  instances  of  the  sacrifice  of  a  temporarily  useless  tissue 
on  behalf  of  tissue  of  high  physiological  value  are  known.  Thus 
the  salmon  and  its  congeners,  which  live  part  of  the  year  in  the  sea, 
lay  their  eggs  and  undergo  their  early  development  in  the  fresh  water 
of  the  upper  reaches  of  rapid  streams.  An  adult  salmon  leaves  the  sea 
in  the  early  summer  months  in  a  magnificent  state  of  muscular  develop- 
ment, fit  to  perform  the  prodigious  feats  of  swimming  which  are 
required  in  order  to  get  it  over  the  rapids  of  the  river  which  it  has  to 


THE  METABOLISM  DURING  STARVATION 


701 


ascend.  It  takes  no  food.  In  the  upper  reaches  of  the  stream  or 
river  there  is  a  growth  of  the  genital  glands,  ovaries,  or  testes.  The 
whole  material  for  the  growth  of  these  large  organs  is  derived  from  the 
atrophy  of  the  skeletal  muscles.  In  this  case  we  have  the  growth  of  an 
active  tissue  at  the  cost  of  an  inactive  one,  the  activity,  however,  being 
determined,  not  by  the  direct  call  upon  it  from  the  environment,  but  by 
what  we  may  speak  of  as  the  '  physiological  habit '  of  the  animal. 

The  animal  organism,  in  the  complete  absence  of  food,  deals  with 
the  resources  of  its  bodily  tissues  with  the  utmost  possible  economy. 
The  total  metabolism  therefore  sinks  rapidly  during  the  first  two 
davs  of  starvation,  and  then  remains  practically  constant.  There 
is  indeed  a  slight  conti)iuous  diminution  with  the  fall  in  body 
weight,  but  if  we  reckon  out  the  total  metabolism  per  kilo  body 
weight,  we  find  that  till  within  a  day  or  two  before  death  it  is  a 
constant  quantity.  This  fact  is  shown  in  the  following  Table  of 
the  output  of  energy  in  man  during  a  five  days'  period  of  starvation 
(Tigerstedt) : 

Metabolism  during  Starvatiok  (Man) 


Day  of 
experiment 

Nitrogen  output 

Fat  oxidised 

Total  calories 

Calories  per  kilo 
body  weight 

1         . 

1216 

204-8 

2231 

33-3 

2       . 

12-85 

190-3 

2112 

32-1 

3       . 

13-62 

179-9 

2032 

31-3 

4 

13-67 

176-4 

2003 

31-3 

5       . 

11-44 

180-0 

1979 

31-4 

Although  in  one  and  the  same  individual  the  total  metabolism 
during  hunger  varies  directly  with  the  body  weight,  this  rule  does 
not  apply  when  we  compare  the  metabolism  of  different  animals 
or  different  examples  of  the  same  species.  We  find,  in  fact,  that 
in  larger  animals  the  metabolism  is  relatively  less  than  in  smaller 
animals,  so  that  if  we  take  the  evolution  of  calories  per  kilo  body 
weight  the  result  is  inversely  proportional  to  the  body  weight.  This 
is  shown  in  the  following  Table,  which  represents  the  total  metabolism 
of  a  number  of  animals  of  different  sizes  (Rubner) : 


Body  weight, 
kilos 

Calorics  per  kilo 
body  weight 

Man        . 
Bogl     . 
Dog  2    . 
Dog  3    . 
Rabbit  1 
Rabbit  2 
Guinea  pig 

70-6 

30-4 

17-7 
3-1 
2-9 
2-05 
0-672 

32-9 
35-3 
45-0 
85-3 
50-2 
58-5 
2231 

702 


PHYSIOLOGY 


On  account  of  the  greater  relative  metabolism  of  smaller  animals, 
their  resistance  to  starvation  is  less  than  that  of  larger  animals.  A 
rat  or  a  mouse  will  only  stand  total  abstinence  from  food  for  two  or 
three  days.  The  difference  is  determined  by  the  fact  that  a  smaller 
animal  has  a  relatively  larger  surface  per  unit  body  weight  than  is 
the  case  with  a  larger  animal.  The  greater  part  of  the  energy  set 
free  during  starvation  is  required  for  the  maintenance  of  the  body 
temperature.  A  larger  amount  of  energy  per  kilo  is  required  in 
those  animals  with  a  relatively  larger  body  surface  through  which 
heat  loss  may  occur.  That  the  difference  in  relative  surface  is  the 
determining  factor  for  the  differences  in  total  metabolism  per  kilo 
body  weight  is  shown  by  the  fact  that,  if  we  reckon  out  the  amount 
of  surface  presented  by  each  of  the  animals  in  the  above  list,  we  find 
that  the  output  of  energy  per  square  metre  of  body  surface  is  approxi- 
mately identical  in  all  cases.  This  is  shown  in  the  following  Table, 
in  which  the  calorie  output  per  square  metre  of  surface  has  been 
reckoned  for  a  number  of  animals  of  different  weight  : 


Body  weight 

Calories  per  square 

metre  body 

surface 

Animal   1 

30-40 

977 

2 

23-70 

1069 

3 

19-20 

1135 

4 

17-70 

1040 

5 

10-90 

1109 

6 

6-45 

1054 

7 

3-10 

1091 

Speaking  roughly,  we  may  say  that  a  wami-blooded  animal 
during  starvation  requires  the  daily  expenditure  of  1000  calories  per 
square  metre  body  surface  in  order  to  maintain  its  temperature  and 
carry  out  such  motor  processes  as  are  essential  to  life. 


THE  METABOLISM  OF  CARBOHYDRATE.  FAT,  AND 
PROTEIN  DURING  STARVATION 
Since  during  starvation  no  energy  is  supplied  to  the  body  from 
without  in  the  shape  of  food-stuffs,  we  can  regard  the  whole  expendi- 
ture of  the  animal  during  its  period  of  starvation  as  occurring  at 
the  expense  of  its  capital.  The  amount  of  carbohydrate  which  can 
be  stored  up  as  glycogen  or  other  forms  is  strictly  hmited.  In  many 
experiments  the  glycogen  metabolism  has  therefore  been  entirely 
disregarded,  and  it  has  been  estimated  that  the  chemical  capital 
of  the  body  consisted  entirely  of  proteins  and  fats.  The  glycogen 
metabohsm,  however,  during  the  first  day  of  a  period  of  starvation 


THE  METABOLISM  DUKING  STARVATION 


703 


may  form  a  considerable  fraction  of  the  total  metabolism  of  the 
body,  and  can  hardly  be  excluded  without  introducing  serious  errors. 
The  relative  parts  played  by  protein,  carbohydrate,  and  fat  respec- 
tively in  the  chemical  exchanges  of  a  starving  animal  may  be  deter- 
mined in  the  following  way :    The  amount  of  protein  consumed  is 
given  by  estimating  the  total  nitrogen  of  the  excreta  by  Kjeldahl's 
method  and  multiplying  the  result  by  the  factor  6-25.     The  loss  of 
weight"  of  the  body  minus  the  protein  consumed  may  be  roughly 
taken  as  equivalent  to  the  fat  plus  carbohydrate  consumption.     But 
this  is  only  a  rough  method,  since  the  quantity  of  water  in  the  tissues 
may  undergo  considerable  variations,  and  so  affect  the  total  weight 
of  the  body.     For  any  accurate  results  the  respiratory  exchanges 
must  be  measured,  including  both  oxygen  intake  and  carbon  dioxide 
output.     After  deducting  the  carbon  dioxide  due  to  the  combustion 
of  the  carbon  of  the  proteins  which  does  not  appear  in  the  urine  in 
combination   wath   nitrogen,   the   remainder  of   the   carbon   dioxide 
is  derived  entirely  from  carbohydrate  and  fat  metabohsm.     Knowing 
the  respiratory  quotient  and  the  total  amount  of  carbohydrate  and  fat 
metabolism,  it  is  possible  to  come  to  a  conclusion  as  to  how  much 
of  the  carbon  dioxide  is  derived  from  oxidation  of  glycogen    and 
how  much  from  the  oxidation  of  fat.     A  very  efficient  check  on  this 
calculation  is  furnished  if  the  individual  or  animal  can  be  placed 
at  the  same  time  in  an  accurate  calorimeter,  as  in  Benedict's  experi- 
ments, owing  to  the  fact  that  a  gramme  of  fat  when  converted  into 
carbon  dioxide  and  water  produces  more  than  double  the  amount 
of  heat  which  would  be  evolved  by  the  complete  oxidation  of  glycogen. 
In  Benedict's  experiments    the  heat-value  of  the  metabolism  cal- 
culated by  the  above  method  agreed  with  the  heat  as  actually  measured 
by  the  calorimeter  within  0-5  per  cent.,  w^hereas  if  the  total  carbon 
of  the  first  day  had  been  reckoned  as  fat,  the  discrepancy  would 
have  been  as  high  as  5  per  cent,  in  many  cases.     The  influence  of 
glycogen  metabolism  on  that  of  protein  during  the  first  and  second 
days  of  fasting  is  shown  in  the  following  experiments  (Benedict)  : 


First  ilay 

Second  day 

Glycogen  metabolised 

N. 
eliminated 

Glycogen  metabolised 

eliminated 

Total 

Per  kilo 

Total 

Per  kilo 

S.A.B.       . 

181-6 

315 

5-84 

29-7 

0-52 

11-04 

S..\.B.      . 

135-3 

2-31 

l()-29 

IS- 1 

0-31 

1 1  -97 

S.A.B.      . 

(!4-9 

1  -09 

12-24 

23-1 

0-39 

12-4.-) 

H.C.K.     . 

KJa-e 

2-33 

9-39 

44-7 

0-04 

14-30 

H.R.D.     . 

32-8 

0-59 

13-25 

41-6 

0-76 

13-53 

704 


PHYSIOLOGY 


The  total  metabolism  per  kilo  body  weight  very  soon  attains  a 
constant  'level.  The  relative  part  taken  in  the  production  of 
the  total  energy  by  fats  and  proteins  respectively  may  vary  from 
animal  to  animal  according  to  the  amount  of  fat  available  in  the 
body.  If  the  animal  has  been  receiving  previous  to  the  experiment 
a  diet  rich  in  protein  the  excretion  of  nitrogen  and  urea  in  the  urine 
diminishes  rapidly  during  the  first  days  of  starvation.  During  the 
first  two  days  therefore  a  considerable  proportion  of  the  necessary 


CM 
UREA 


\ 

SO 

\ 

\ 

AO 

\ 

30 

\ 

20 

N 

\, 

N, 

s 

V 

-^ 

10 

"*~ 

-- 

•^.^ 

^* 

^— ^ 



-^ 

—^ 

*=* 

=*=: 

rr^ 

^^ 

^ 

A 

Fig.  318.     Three  experiments  on  the  output  of  urea  during  starvation  (dog). 
(TiGEESTEDT  after  VoiT.) 
In  (1)  (thin  line),  the  dog  received  2500  grm.  meat  per  day  before  the 
experiment ;  in  (2)  (thick  line),  the  diet  was  1.500  grm.  meat ;  and  in  the  third 
experiment  the  meat  was  reduced  to  a  minimum. 


energy  is  obtained  at  the  expense  of  protein.  Between  the  third 
and  fifth  day,  however,  the  nitrogenous  excretion  reaches  a  minimum, 
at  which  point  it  remains  approximately  constant  to  within  a  day 
or  two  before  death.  If  the  animal  has  been  receiving  a  diet  very 
poor  in  protein  the  excretion  of  nitrogen  may  be  low  throughout  the 
whole  course  of  the  experiment.  These  facts  are  illustrated  by  the 
curves  in  Fig.  318,  which  show  the  output  of  urea  in  three  experiments 
on  a  dog  under  different  conditions  of  nutrition.  In  the  first  experi- 
ment the  dog,  before  the  experimental  period,  had  been  receiving 
2500  grm.  of  meat  daily  ;  in  the  second  it  had  been  receiving 
1500  grm.  of  meat,  and  in  the  third  only  a  small  quantity,  which 
was  not  accurately  measured.  Although  there  is  a  great  difference 
between  the  urea  output  during  the  first  day  of  the  experiments, 


THE  METABOLISM  DURING  STARVATION  705 

the  urea  output  during  the  sixth  to  eighth  days  is  identical.  In 
many  cases  for  a  few  days  before  death  there  is  a  rise  of  protein 
metabolism.  This  rise  is  synchronous  with  a  practically  complete 
disappearance  of  fat  from  the  body.  The  animal  now  has  to  supply 
all  its  requirements  at  the  expense  of  the  protein  tissues,  which 
therefore  waste  rapidly  and  account  for  the  increased  excretion 
of  nitrogen.     This  is  shown  in  the  following  experiment  of  Rubner's 

on  a  rabbit  : 

..  Average  daily  out-  Average  amount  of 

^^®  put  of  nitrogen  fat  oxidised  daily 

1-3  .  .  .  .  1-67  grm.  ..  10-3  grm. 

4-5  ...         .  1-46     „  ..  10-3     „ 

6-8  .         .         .  .  3-21     „  ..  2-4    „ 

We  see  therefore  that  during  starvation,  apart  from  the  first 
day  or  two,  the  animal  derives  the  main  portion  of  its  necessary 
energy  from  the  combustion  of  fats,  provided  that  there  is  a  sufl6.cient 
store  of  these  substances  in  the  body.  A  certain  consumption  of 
protein  is  unavoidable.  Since  protein  comes  from  the  working 
tissues  of  the  body  they  are  spared  so  far  as  possible,  and  it  is 
only  when  the  stored  fat  is  used  up  that  any  large  call  is  made  on 
the  tissue -protein. 


46 


SECTION  III 

THE  EFFECT  OF  FOOD  ON  THE  METABOLISM 
OF  THE  BODY 

A  MARKED  contrast  exists  between  protein  and  the  other  two 
classes  of  food-stuffs  in  relation  to  nutrition.  Whereas  it  is  pos- 
sible in  the  case  of  many  animals  to  maintain  life  with  a  diet 
consisting  of  proteins,  salts,  and  water,  such  as  is  contained  in 
the  leanest  possible  meat,  a  diet  of  pure  fat  or  carbohydrate,  or 
a  mixture  of  the  two,  is  almost  equivalent  to  an  absolute  abstinence 
from  food,  the  animal  on  such  a  diet  surviving  only  a  few  days 
longer  than  during  complete  starvation.  The  primary  importance 
of  proteins  in  nutrition  therefore  indicates  that  it  is  advisable  to 
deal  first  with  the  effects  on  metabolism  of  a  diet  consisting  of  this 
food-stuff  alone.  In  an  animal  which  has  been  starved  for  five  or 
six  days  the  nitrogenous  output  of  the  body  has  attained  a  prac- 
tically constant  level,  varying  with  the  size  of  the  animal  and  with 
the  relative  content  of  its  body  in  fat.  Let  us  assume  that  such 
an  animal  is  excreting  5  grm.  of  nitrogen  daily,  corresponding  to 
a  protein  metabolism  of  31-25  grm.  of  protein.  It  might  be 
thought  that  this  loss  of  protein  to  the  body  would  be  met  if  we 
administered  to  the  animal  as  food  a  similar  amount,  i.e.  31-25  grm. 
of  protein.  On  trying  the  experiment,  however,  we  find  the  effect 
of  giving  protein  food  is  to  increase  largely  the  nitrogenous  out- 
put of  the  body,  so  that  after  receiving  this  amount  of  protein 
the  animal's  nitrogenous  excretion  will  amount  to  nearly  10  grm. 
The  waste  of  tissue-protein  in  the  body  therefore  proceeds.  In 
order  to  stop  this  waste,  i.e.  to  ensure  that  the  animal  does  not  lose 
more  nitrogen  than  it  receives  in  its  food,  we  must  give  an  amount 
of  protein  corresponding  to  between  two  and  a  half  and  five  times 
the  amount  of  protein  which  undergoes  disintegration  during  starva- 
tion. The  reason  for  this  is  obvious  on  reference  to  p.  701.  There 
we  see  that  a  man  on  the  fifth  day  of  starvation  excreted  11-44  grm. 
of  nitrogen,  corresponding  to  71-5  grm.  of  protein.  This  protein 
metabolism  did  not,  however,  represent  the  sole  source  of  the  energy 
output  of  the  body.  The  total  energy  output  was  1979  calories.  Of 
this  amount  only  293  calories  could  be  obtained  from  the  combustion 
of  the  71  grm.  of  protein,  the  balance  being  due  to  the  oxidation  of 

706 


THE  EFFECT  OF  FOOD  ON  METABOLISM  707 

fat  stored  up  in  the  body.  This  signifies  that  only  one-fifth  of  the 
total  energy  requirements  of  the  body  were  supphed  at  the  expense 
of  protein.  We  cannot  therefore  expect  to  stop  loss  of  body  substance 
by  giving  an  amount  of  protein  food  which  would  correspond  only 
to  one-fifth  of  the  energy  requirements.  The  same  ratio  between 
protein  metabolism  and  total  energy  output  of  the  body  is  shown 
in  the  Table,  p.  710,  from  experiments  on  animals.  In  most  cases, 
if  we  are  dealing  with  an  animal  with  a  considerable  store  of  fat  in 
its  body,  nitrogenous  equihbrium,  i.e.  an  equivalence  between  income 
and  output  of  nitrogen,  is  attained  with  a  quantity  of  protein  in  the 
food  which  is  less  than  five  times  the  amount  lost  during  starvation. 
In  such  a  case  the  total  energy  requirements  of  the  body  are  met 
not  only  at  the  expense  of  the  protein  food  but  also  at  the  expense 
of  the  fat  of  the  tissues.  The  animal  will  continue  to  lose  weight 
and  to  become  thin,  although  he  is  in  a  state  of  nitrogenous  equihbrium. 
The  protein  taken  in  with  the  food  on  a  pure  protein  diet  has  a 
twofold  function  to  perform.  In  the  first  place,  every  functional 
activity  of  the  living  tissues  is  probably  associated  with  a  certani 
amount  of  wear  and  tear,  and  results  in  the  production  of  disintegration 
products  which  are  not  in  a  condition  to  be  resynthetised  into  living 
working  protoplasm.  We  know,  for  instance,  that  from  every 
mucous  surface  dead  cells  are  being  continually  cast  off  and  that  a 
constant  disintegxation  of  red  blood  corpuscles  goes  on,  resulting 
in  the  production  of  the  bile  pigments  ;  and  we  are  warranted  in 
extending  the  operation  of  these  changes  of  which  we  have  ocular 
evidence  to  the  case  of  other  cells,  such  as  those  of  the  liver  and 
of  the  muscles,  where  direct  proof  of  destruction  of  tissue  during 
normal  metaboHsm  is  more  difficult  to  obtain.  We  shall  have  occasion 
to  discuss  later  on  the  extent  of  this  process  of  disintegration.  It  is 
certain  that  some  portion  of  the  nitrogen  excreted  during  complete 
starvation  must  come  from  this  source,  and  that  one  of  the  functions 
of  protein  food  is  the  replacement  of  tissue  which  has  been  lost  in 
this  way.  When,  however,  we  are  feeding  an  animal  on  a  pure  protein 
diet,  by  far  the  larger  portion  of  the  food  is  utilised  for  meeting  the 
energy  requirements  of  the  body.  In  this  function  protein  food, 
apart  from  accidents  of  digestibility  and  structural  adaptation  of 
the  animal's  digestive  arrangements  to  its  habits  of  life,  presents  no 
apparent  advantages  over  the  other  two  classes  of  food-stuffs.  Its 
value  to  the  animal  is  represented  by  its  physiological  heat-value. 
It  may  be  represented  therefore  numerically  as  -i-l,  and  is  equivalent 
to  the  value  of  carbohydrate*  and  is  far  inferior  to  the  value  of  fats 
with  a  heat  equivalent  of  9-3.     If,  instead  of  giving  to  the  starving 

*  This  may  be  expressed  by  saying  that   protein  is  isodynaniic  with  an 
equal  weight  of  carboliydrate. 


708 


PHYSIOLOGY 


animal  a  pure  protein  diet,  we  administer  a  mixed  diet  containing  a 
sufficient  quantity  of  fat  or  carbohydrate,  or  of  both  substances,  to 
meet  the  normal  energy  requirements  of  the  body,  we  can  restrict 
the  utilisation  of  protein  more  nearly  to  the  replacement  of  tissue 
waste  in  the  body,  and  are  therefore  able  to  attain  nitrogenous 
equilibrium  with  a  much  smaller  proportion  of  protein  than  is  possible 
when  this  substance  furnishes  the  whole  diet.  In  carnivora,  which 
have  the  habit  of  supplying  a  large  proportion  of  their  energy  needs 
at  the  expense  of  protein,  the  amount  of  carbohydrate  and  fat  which 
must  be  added  to  protein  in  order  to  attain  nitrogenous  equilibrium 
with  a  nitrogenous  output  equal  to  that  in  starvation  is  very  large 
and  corresponds  to  an  energy-value  in  excess  of  the  total  energy 
expenditure  during  starvation.  In  omnivora,  such  as  man,  it  is 
easy  to  attain  nitrogenous  equilibrium  on  a  mixed  diet  with  a  smaller 
nitrogen  turnover  than  is  found  during  starvation.  In  the  experi- 
ment given  on  p.  701  the  average  nitrogen  output  during  starvation 
was  about  12  grm.  of  nitrogen.  In  Succi,  the  fasting  man,  the  nitro- 
gen output  varied  from  11-19  grm.  on  the  fifth  day  to  2-82  grm.  on 
the  twenty- first  day. 

Daily  Nitrogen  Excretion  of  Succi  in  Starvation 


Day 

N. 

Day 

N. 

Day 

N. 

1   .    .    .  170 

8  . 

.   9-74 

15 

.  505 

2 

11-2 

9  . 

.  1005 

16 

.  4-32 

3 

10-55 

10  . 

.   712 

17 

.  5-4 

4 

10-8 

11  . 

.   6-23 

18 

.  3-6 

5 

1119 

12  . 

.   6-84 

19 

.  5-7 

6 

1101 

13  . 

.   514 

20 

.  3-3 

7 

8-79 

14  . 

.   4-66 

21 

.  2-82 

Chittenden  has  shown  that  in  man  a  perfectly  normal  nutrition 
may  be  maintained  on  a  mixed  diet  containing  about  7  grm.  of  nitro- 
gen daily.  In  the  cases  investigated  by  Chittenden  the  energy 
output  of  the  men  could  be  regarded  as  normal,  corresponding  to 
32-35  calories  per  kilo  body  weight.  If  the  amount  of  fat  and 
carbohydrate  be  very  largely  increased  it  is  possible  to  maintain 
nitrogenous  equihbrium  on  even  smaller  quantities  of  protein.  Thus 
nitrogenous  equilibrium  was  attained  by  Siven  on  a  diet  containing 
33  grm.  of  protein  daily  (=  4  grm.  of  nitrogen),  but  in  this  case  the 
carbohydrates  and  fats  were  increased  to  such  an  extent  that  the  man 
was  taking  in  78-5  calories  per  kilo  per  day.  These  results  suggest 
that  the  quaUtative  metabohsm  of  the  body  is  determined  by  the 
relative  amount  of  food-stuff  supphed  to  the  body  and  circulating 
in  its  juices  at  any  given  time,  and  that  preponderance  of  one  food- 
stuff will  tend  to  excite  the  cells  of  the  body  to  the  utilisation  of  this 
food-stuff  at  the  expense  of  the  other  two.     That  such  is  the  case  is 


THE  EFFECT  OF  FOOD  ON  METABOLISM 


im 


shown  by  a  study  of  the  effect  of   increasing  each  class  of  food  on 
the  metabolism  of  the  body  as  a  whole. 


EFFECTS  OF  VARIATIONS  IN  PROTEIN 
Most  of  the  experiments  on  the  influence  of  variations  in  the 
quantity  of  protein  food  have  been  made  on  carnivora,  such  as 
the  dog  and  cat.  Within  very  wide  limits  the  output  of  nitrogen 
is  proportional  to  the  intake.  This  is  shown  in  the  following  Tables 
by  Voit,  representing  two  experiments  on  dogs  : 


EXPERDIENT  I 

Experiment  II 

I)ay 

Daily  meat 
ration 

Flesh  loss 
pi-r  day 

Bay 

Daily  meat 
ration 

Flesh  loss 
per  day 

1 

2 
3 
4 

5 
0 
7 

8 

500 
1500 
1500 

1500 
1500 
1.500 
15W 
1500 

547 
1222 
1310 
1390 
1410 
1440 
1450 
1500 

1     . 

2 

3  . 

4  . 

5  . 

6  . 

1500 
1000 
1000 
1000 
1000 
1000 

1500 
1153 
1086 
1088 
1080 
1027 

In  Experiment  I  the  animal  had  been  fed  for  some  days  with 
500  grm.  of  meat  per  diem.  The  fact  that  he  was  excreting  nitrogen 
corresponding  to  547  grm.  shows  that  this  amount  was  insufficient 
and  that  he  was  not  yet  in  a  condition  of  nitrogenous  equilibrium. 
Each  day  he  was  using  up  47  grm.  of  the  protein  of  his  body  in  addition 
to  the  500  ,grm.  supplied  in  the  food.  On  increasing  his  food  three- 
fold to  1500  grm.  the  nitrogenous  output  was  also  increased,  but  a 
state  of  nitrogenous  equilibrium  was  not  reached  until  the  eighth 
day  of  the  experiment.  During  the  six  days  intervening  778  grm. 
of  meat  had  been  retained  in  the  body,  i.e.  there  had  been  a  retention 
of  protein,  probably  in  the  form  of  increased  muscular  substance. 
The  amount  is  too  great  to  be  accounted  for  by  retention  of  the 
disintegration  products  of  the  protein  in  the  body.  It  must  have 
been  stored  up  in  the  form  of  protein  and  probably,  to  a  large  extent 
at  any  rate,  as  actual  living  tissue. 

In  the  second  experiment  the  diminution  of  the  protein  of  the 
food  was  followed  by  a  loss  of  protein  from  the  body,  the  output  being 
greater  than  the  income.  The  excess,  however,  vms  rapidly  diminishing 
and  equilibrium  had  been  practically  attained  on  the  last  day  of 
the  experiment.  During  this  time  the  animal  had  excreted  14-8  grm. 
of  nitrogen  more  than   it  had  received  in   its  food,   which  would 


710 


PHYSIOLOGY 


correspond  to  a  diminution  of  the  protein  store  of  its  body,  reckoned 
as  muscular  substance,  by  434  grm.  Many  such  experiments  have 
been  performed,  and  'they  all  agree  in  showing  that  in  carnivora  a 
very  appreciable  storage  of  nitrogen  can  take  place  in  the  body. 
In  cats  it  is  sometimes  possible  to  double  the  body  weight  by  adminis- 
tration of  a  large  protein  diet.  Since  no  fat  is  laid  on  at  the  same 
time  and  the  animals  are  in  a  fine  healthy  condition,  one  must  con- 
clude that  the  greater  portion  of  the  storage  takes  place  by  a  growth 
of  muscle  substance.  The  degree  to  which  the  storage  can  take 
place  is,  however,  variable  and  is  generally  smaller  in  dogs  than  m 
cats.  However  much  protein  is  given,  the  limit  is  finally  arrived  at 
where  no  further  laying  on  of  protein  tissues  of  the  body  is  possible, 
and  the  animal  then  enters  into  a  state  of  nitrogenous  equilibrium, 
when  he  excretes  a  quantity  of  nitrogen  exactly  equal  to  that  taken 
in.  This  equivalence  of  income  and  output  signifies  that  the  extent 
of  the  total  metabolism  of  the  body  is  affected  by  the  amount  of 
protein  supplied  in  the  food,  and,  as  a  matter  of  fact,  the  total  energy 
output  of  the  body  rises  and  falls  with  the  quantity  of  protein  in  the 
food.  This  is  shown  in  the  following  Table  by  Pettenkofer  and  Voit, 
in  which  the  figures  have  been  recalculated  by  Pfliiger : 


Nit  rotten  ill  food 

Niti'oj^'cii  output 

Kat  gain  or  loss 

Total  calories 

1 

0 

5-61 

-98 

1067 

2       . 

17 

20-37 

-61 

1106 

3       . 

34 

36-69 

-43 

1360 

4 

51 

51-00 

-24 

1552 

5 

61 

59-74 

-36 

1893 

6 

68 

69-50 

+   8 

1741 

7 

85 

85-41 

+   4 

2181             I 

We  see  therefore  that  carnivorous  animals  can  satisfy  their  total 
energy  requirements  at  the  expense  of  protein.  When  the  protein 
income  is  in  excess  of  their  requirements  a  small  amount  is  laid  on, 
probably  in  the  shape  of  increased  muscular  tissue.  The  most 
marked  effect  is,  however,  an  increased  metabolism  which  rises  in 
proportion  to  the  nitrogenous  income.  The  limit  to  this  increase  is 
set  by  the  powers  of  the  alimentary  canal  to  digest  the  protein.  The 
rise  in  metabolism  consequent  on  protein  food  is  very  rapid  and 
affects  the  gaseous  exchanges  as  well  as  the  output  of  nitrogen. 
Magnus  Levy  and  Falk  found  that  a  large  protein  meal  might 
increase  the  respiratory  exchanges  40  per  cent.,  an  increase  which 
lasted  seven  hours.  The  nitrogenous  output  also  rises  immediately 
after  a  protein  meal,  so  that  50  per  cent,  of  the  nitrogen  of  the  ingesta 
may  appear  in  the  urine  within  seven  hours  after  the  meal. 


THE  EFFECT  OF  FOOD  ON  METABOLISM  7J1 

The  whole  of  these  results  cannot  be  strictly  applied  to  omnivorous 
animals,  such  as  man.  In  these  it  is  impossible  to  supply  all  the 
energy  requirements  of  the  body  on  a  pure  protein  diet.  Even  if 
a  man  eats  as  much  meat  as  he  can,  he  will  be  unable  to  obtain  suffi- 
cient energy  for  his  daily  requirements.  Whereas  the  average  daily 
requirements  of  a  man  amount  to  about  3000  calories,  1  lb.  of  meat 
would  yield  only  about  400  calories,  and  even  if  he  took  4  lb.  of 
meat  daily,  an  amount  which  is  impossible  for  most  individuals, 
he  would  only  be  obtaining  about  1600  calories.  The  cures  for 
obesity,  in  which  a  large  protein  diet  plays  an  important  part,  owe 
their  efficiency  to  this  fact.  They  are  in  all  cases  practically  equi- 
valent to  a  state  of  semi-starvation.  Many  experiments  have  been 
made  on  the  influence  of  variations  in  the  quantity  of  protein  in  a 
mixed  diet.  Within  wide  limits  the  output  of  nitrogen  is  strictly 
proportional  to  the  intake.  A  normal  adult  man  seems  to  be  unable 
to  store  up  protein  in  any  form,  and  differs  in  this  respect  from 
carnivora,  such  as  the  dog  or  cat.  The  only  way  in  which  protein  can 
be  laid  on  in  the  body  is  by  furnishing  a  physiological  stimulus  to  the 
growth  of  muscle,  i.e.  by  constant  exercise.  Without  this  it  is  not 
possible  to  produce  growth  of  the  muscles  of  the  body,  however  much 
protein  we  may  give  in  the  diet.  The  conditions  are,  however,  different 
when  dealing  with  an  individual  in  whom  from  some  cause  or  other 
the  muscular  tissues  have  not  attained  their  full  development.  Thus 
in  growing  individuals  a  certain  amount  of  the  protein  of  the  food 
is  always  retained  in  the  body  and  laid  on  as  tissue-protein.  In 
convalescence  after  severe  fever,  during  which  a  great  wasting  of 
the  muscles  has  taken  place,  forced  feeding  with  large  amounts 
of  protein  has  been  found  to  give  rise  to  a  considerable  retention  of 
jjrotein  in  the  body.  This  process  only  goes  on  until  the  muscles 
have  attained  their  normal  condition  of  development.  When  the 
tissues  have,  so  to  speak,  reached  '  par,'  the  possibility  of  laying 
on  protein  tissues  ceases.  On  the  other  hand,  protein  food  has  in  man, 
as  in  animals,  a  specific  stimulating  effect  on  metabolism,  so  that  the 
respiratory  exchanges  are  largely  increased  as  a  result  of  a  heavy 
protein  meal.  This  effect  has  been  named  by  Rubner  the  '  specific 
dynamic  effect  '  of  protein.  We  shall  have  occasion  later  to  discuss 
its  significance. 

THE  INFLUENCE  OF  FATS  AND  CARBOHYDRATES 
If  either  fats  or  carbohydrates  be  given  to  a  starving  animal 
a  certain  sparing  of  the  fat  of  the  body  takes  place,  but  this  effect, 
according  to  some  observers,  is  accompanied  by  a  distinct  increase 
in  the  metabolic  exchanges  of  the  body.  As  regards  the  protein 
metabolism,  Cathcart  finds  that  while  administration  of  fat  increases 


712  PHYSIOLOGY 

the  nitrogen  output  during  starvation,  carbohydrate  food  causes  a 
diminution  in  the  nitrogen  output,  and  thus  exercises  a  marked 
sparing  effect  on  the  proteins  of  the  body.  Voit  found  that  during 
starvation  or  with  an  insufficient  protein  diet  addition  of  fat  to  the 
food  increased  the  total  metabohsm.  When  sufficient  protein  was 
being  suppHed,  the  addition  of  fat  caused  no  increase  in  the  total 
metabolism,  the  whole  of  the  fat  in  the  food  being  laid  on  as  fat  in 
the  body.  The  stimulating  effect  of  fat  on  metabolism  is  but  slight. 
Magnus  Levy  found  that  the  increase  in  the  metabolism  on  the 
administration  of  fat  to  a  starving  animal  was  minimal  and  never 
exceeded  10  per  cent. 

Carbohydrates  have  a  somewhat  greater  influence  on  meta- 
bolism. The  administration  of  a  large  meal  of  carbohydrates  to  a 
starving  animal  may  raise  the  respiratory  exchanges  from  20  to 
30  per  cent.,  and  the  increase  may  last  four  hours  after  the  meal. 
This  stimulating  influence  on  metabohsm  is,  however,  much  less  than 
that  observed  on  the  administration  of  large  doses  of  protein.  If 
carbohydrate  be  given  in  excess  of  the  daily  energy  requirements 
the  greater  proportion  of  it  remains  in  the  body,  being  stored  up  to 
a  small  extent  as  glycogen,  but  mainly  in  the  form  of  fat. 


SECTION  IV 

THE  EFFECT  OF  MUSCULAR  WORK  ON 
METABOLISM 

When  an  animal  performs  muscular  work  its  total  output  of  energy 
must  be  increased,  and  this  must  take  place  at  the  expense  either 
of  an  increased  intake  of  food  or  an  increased  destruction  of  the 
tissues  of  the  body.  For  many  years  a  theory  put  forward  by  Liebig 
received  universal  acceptance  among  physiologists.  According  to 
this  view  the  food-stuffs  could  be  divided  into  two  classes,  namely, 
the  proteins,  which  were  the  plastic  food  substances  and  were  con- 
cerned in  the  building  up  of  tissues,  and,  secondly,  the  fats  and  carbo- 
hydrates, which  took  no  part  in  the  building  of  the  tissues,  but  were 
oxidised  for  supplying  heat  to  the  body.  Muscular  work  was  sup- 
posed to  be  attended  with  a  breakdown  of  the  muscular  tissue, 
and  therefore  to  be  performed  at  the  expense  of  an  increased  protein 
metabohsm,  which  had  to  be  made  good  by  adding  to  the  protein 
intake  in  the  food.  If  this  view  were  correct  one  would  expect  to 
find  a  great  increase  in  the  nitrogenous  metabolism  of  the  body  with 
every  increase  in  muscular  work.  Such  an  increase  has,  in  fa^t,  been 
found  by  Pfliiger  in  dogs  which  were  nourished  on  a  purely  protein 
diet.  In  these  animals  the  sole  source  of  energy  to  the  organism  was 
protein,  and  therefore  any  additional  call  on  the  energies  of  the  body 
must  be  associated  with  an  increased  intake  of  food  or  an  increased 
loss  of  material  from  the  body  in  the  shape  of  protein.  In  an  animal 
which  is  enjoying  a  normal  mixed  diet,  or  has  a  store  of  carbonaceous 
material  in  its  tissues  in  the  shape  of  fat,  there  is  no  increase  of  nitro- 
genous metabolism  during  muscular  work  which  would  correspond  in 
any  way  to  the  amount  of  work  done.  This  was  shown  long  ago  by 
Voit  in  experiments  on  the  dog.  The  following  Table  represents  the 
nitrogenous  metabolism,  i.e.  the  amount  of  muscular  material  in  the 
shape  of  protein  metabolised  during  the  day,  under  varying  conditions 
of  rest  and  activity,  during  starvation  and  after  food  : 


Food  Flesh  metabDlisni  (Vtnflitinn  <>f  <1 

0         .  .  . 

0         .  .  . 


Dog  I 

Flesh  metabDlisni 

(Vtnflitinn  <>1 

Gnn. 

164 

H.M 

167 

Work 

149 

Rest 

713 

714 


PHYSIOLOGY 

Dog  II 

F(jod 

Flesh  metabulibiii 
Gmi. 

Cuuditiou  of  dug 

1500  gna. 

lean  moat     .          1522 

Rest 

1500    „ 

1625 

Work 

1500    „ 

1526 

Rest 

1500    „ 

1583 

Work 

1500    „ 

1535 

Rest 

During  the  work  days  the  animal  performed  about  1500  kilo- 
gramme metres  in  the  day.  The  differences  in  the  protein  meta- 
bolism between  the  rest  and  the  work  days  are  thus  practically 
insignificant,  the  nitrogenous  output  being  determined,  not  by  the 
work  done,  but  by  the  amount  of  protein  administered  in  the  food. 
In  the  second  experiment  there  is  an  average  increase  of  protein 
metabolism  during  the  work  days  amounting  to  86  grm.  of  flesh, 
a  quantity  which  is  insufficient  to  furnish  the  energy  of  the  work 
done.  The  same  results  were  arrived  at  in  a  classical  experiment 
performed  by  Fick  and  Wislicenus  on  themselves,  in  which  they 
measured  their  total  nitrogenous  metabolism  during  an  ascent  of 
the  Faulhorn  from  the  Lake  of  Brienz.  The  vertical  distance  tra- 
versed was  1956  metres.  During  the  seventeen  hours  before  the 
experiment,  the  six  hours  of  the  ascent,  and  the  seven  subsequent 
hours  they  ate  food  practically  free  from  nitrogen.  The  urine 
passed  during  the  ascent  and  during  the  next  seven  hours  was  collected 
in  each  case  and  its  nitrogen  determined.  Fick  passed  5-74  grm.  of 
nitrogen,  which,  if  the  energy  of  the  protein  were  totally  converted 
into  work,  would  correspond  to  63,378  kilogramme  metres.  In  Wis- 
licenus the  amount  was  5-55  grm.  of  nitrogen,  equivalent  to  61,280 
kilogramme  metres.  Fick,  who  weighed  66  kilos,  in  raising  himself  to  a 
height  of  1956  metres,  had  performed  129,096  kilogramme  metres,  and 
Wislicenus,  with  a  weight  of  76  kilos,  had  performed  148,656  kilo- 
gramme metres.  Even  if  we  assume  the  possibility  of  a  conversion 
of  the  ^oto^  energy  of  the  protein  metabolised  during  the  experiment 
into  mechanical  energy,  we  cannot  account  for  more  than  half  of 
the  total  work  done.  All  subsequent  experimenters  have  confirmed 
the  deductions  which  were  drawn  from  these  two  researches,  namely 
that  muscular  work,  while  practically  without  influence  on  nitro- 
genous metabolism,  increases  enormously  the  carbonaceous  meta- 
bolism of  the  body,  so  that,  except"  in  the  rare  cases  where  the  diet 
consists  of  pure  protein  and  the  body  is  practically  free  from 
fat,  the  additional  energy  output  during  work  is  derived  from  the 
oxidation  of  carbon  and  hydrogen  to  carbon  dioxide  and  water. 

The  general  nature  of  the  changes  in  the  metabolism  of  the  body 
during  work  is  well  illustrated  by  the  results  obtained  by  Atwater  on 


EFFECT  OF  MUSCULAR  WORK  ON  METABOLISM     7l."» 

man.  The  total  energy  output  of  a  man  was  reckoned  as  heat  by 
means  of  the  calorimeter.  The  heat  equivalent  of  the  external 
muscular  work  performed  by  the  man  was  also  reckoned  as  heat. 
In  the  following  Table  we  give  the  total  output  of  energy  per  day 
during  rest  and  work,  the  latter  being  also  expressed  in  calories*  : 

Energy  per  Day 


Kature  of  txixriniint 

Heat  eliminated 

External 
work  in 
calories 

Total 
in 

calories 

By  radiation 

and 
conduction 

In  urine 
and 

In  water 
vaporised 
from  luuRS 
and  skin 

Rest  with  food  (average 
of  four  days) 

Rest  fasting  (four  experi- 
ments)    (average     of 
five  days) 

Work   (fourteen   experi- 
ments)    (average     of 
forty-six  days) 

18.50 
1605 

3802 

26 
21 

29 

.521 
561 

743 

546 

2397 
2187 

5120 

If  we  compare  the  energy- value  of  the  work  done  with  the  excess 
of  the  total  expenditure  of  the  body  over  that  found  during  the  rest 
experiments,  we  find  that  the  performance  of  muscular  work  involves 
an  increase  in  the  total  energy-expenditure  of  the  body  by  an  amount 
equal  to  about  five  times  that  of  the  work  done.  Of  course  a  certain 
proportion  of  this  excess  of  energy  over  work  done  is  accounted  for 
by  the  increase  in  the  work  which  must  be  performed  by  the  respira- 
tory muscles  and  heart  in  the  state  of  greater  activity  which  is 
imposed  upon  them  by  the  external  work,  and  is  necessary  for  the 
proper  provision  of  the  active  muscles  with  increased  food-supply 
and  oxygen.  Even  if  we  neglect  these  factors  altogether,  we  see 
that  the  efficiency  of  the  body  as  a  machine  corresponds  to  between 
16  and  20  per  cent.,  an  efficiency  which  exceeds  that  of  the  best  of 
our  steam-engines  and  is  only  equalled  by  certain  internal-combustion 
engines. 

A  comparison  of  the  excreta  of  the  same  individual  whose  energy 
exchanges  are  given  in  the  above  Table  during  rest  and  activity 
will  give  us  information  as  to  the  source  of  the  increased  energy 
put  out  during  the  performance  of  muscular  work.  Thus  during 
a  period  of  rest  and  starvation  the  average  output  of  carbon  dioxide 

*  One  large  calorie,  or  *  kilo-calorie,'  is  tquivalent  to  425  kilogrammelres. 


716  PHYSIOLOGY 

during  six  hours  amounted  to  189-6  grm. ;  during  a  rest  experiment 
with  food  the  average  output  for  a  period  of  six  hours  was  230*4  grm. 
of  carbon  dioxide.  During  work  the  average  output  in  the  same 
individual  during  six  hours  rose  to  705  grm.  of  carbon  dioxide  on  a 
carbohydrate  diet,  and  to  634-8  grm.  on  a  diet  containing  a  large 
amount  of  fat.  The  oxidation  of  carbon  was  therefore  increased 
more  than  threefold  as  a  result  of  muscular  work.  If  we  compare 
in  the  same  way  the  protein  metaboHsm  of  the  same  individual 
during  these  experiments  no  such  alteration  is  observed.  Thus  the 
average  output  per  day  during  rest  and  starvation  corresponded 
to  82  grm.  of  protein.  During  rest  and  with  an  approximately  suffi- 
cient amount  of  food  the  average  amount  of  protein  consumed  was 
98-8  grm.  During  a  work  day  in  which  he  received  practically  the  same 
amount  of  protein  in  the  food  and  a  somewhat  insufficient  amount 
of  carbohydrates  and  fats,  his  consumption  of  protein  amounted 
to  109-4  grm.  Here,  as  against  a  three-  to  fourfold  increase  of  the 
gaseous  metabolism  of  the  body,  we  have  only  a  10  per  cent, 
increase  of  the  protein  metabolism. 

There  is  another  method  by  which  we  can  arrive  at  some  idea 
of  the  nature  of  the  material  which  is  furnishing  by  its  oxidation 
the  necessary  energy  for  the  performance  of  muscular  work.  It  is 
evident,  if  we  compare  the  formulae  of  a  carbohydrate  and  a  fat 
respectively,  that  it  will  require  a  relatively  larger  amount  of  oxygen 
to  oxidise  the  fat  than  is  necessary  in  the  case  of  the  carbohydrate. 
In  the  latter  there  is  sufficient  oxygen  to  combine  with  all  the  hydro- 
gen present  and  form  water.  The  whole  of  the  oxygen  therefore 
which  is  taken  in  is  employed  in  the  oxidation  of  the  carbon,  and 
one  volume  of  oxygen  will  produce  one  volume  of  carbon  dioxide. 
Thus  :  CfiHiaOe  +  6O2  =  6H2O  +  6CO2.  If  the  whole  of  the 
animal's  energy  requirements  were  furnished  by  the  oxidation 
of  carbohydrates,  the  output  of  carbon  dioxide  expired  would  be 
exactly  equal  in  volume  to  the  oxygen  inspired,  and  the  respiratory 

CO2  expired 
quotient  of  the  animal,  namely,  -tt — : -. — .,  would  be  equal  to  unity. 

In  fats  the  amount  of  oxygen  is  only  sufficient  to  combine  with  four 
atoms  of  the  hydrogen  of  the  molecule.  When  fats  undergo  oxida- 
tion, of  the  oxygen  used  only  a  portion  is  devoted  to  the  formation 
of  carbon  dioxide,  the  rest  being  employed  in  the  oxidation  of  hydro- 
gen to  water.  In  an  animal  using  only  fats  the  carbon  dioxide  output 
of  the  body  would  be  considerably  less  than  the  oxygen  intake  and 
its  respiratory  quotient  would  be  less  than  unity.  The  respiratory 
quotients  for  protein,  fats,  and  carbohydrates  are  given  in  the 
following  Table  (Atwater) : 


EFFECT  OF  MUSCULAR  WORK  ON  METABOLISM     717 


Material 

r,            .                                    .             CO.. 

Respiratory  quotient  — j-p 

Starch 

10 

Cane  sugar 
Glucose 

10 
10 

Animal  fat     . 

0-711 

Protein 

0-809 

The  respiratory  quotient  in  an  animal  at  any  given  time  is  there- 
fore determined  by  the  nature  of  the  substances  which  are  under- 
going oxidation  in  its  body.  If  the  performance  of  muscular  work 
involved  special  chemical  processes,  a  metabolism  of  one  of  the 
main  constituents  of  the  body  in  preference  to  either  of  the  others, 
this  sudden  change  in  the  quality  of  the  metabohsm  should  show 
itself  in  the  respiratory  quotient.  It  has  been  proved,  however, 
by  Speck  and  Lowy  that  moderate  muscular  work,  i.e.  work  which 
is  not  associated  with  dyspnoea  and  deficient  oxygenation  of  the 
muscles,  although  attended  by  a  large  increase  both  in  the  carbon 
dioxide  output  and  the  oxygen  intake  of  the  body,  does  not  disturb 
in  any  degree  the  relation  between  these  two  substances,  i.e.  the 
respiratory  quotient.  This  result  indicates  that  the  metabolism 
of  the  body  which  furnishes  the  energy  of  muscular  acti\nty  is  qualita- 
tively of  the  same  nature  as  that  which  occurs  during  rest,  i.e.  that 
the  energy  for  muscular  contraction  can  be  derived  from  any  or 
all  of  the  three  classes  of  food-stuffs  or  proximate  constituents 
of  the  body. 


SECTION  V 

THE  SIGNIFICANCE  OF  THE  FOOD-STUFFS 

When  the  proteins  are  taken  as  food  they  are  rapidly  and  almost 
completely  metabolised,  so  that  the  energy  output  of  the  body 
increases  pari  passu  with  the  increased  protein  food.  With  a  large 
excess  of  protein,  a  certain  limited  storage  of  this  material  is  possible, 
but  the  stored-up  protein  rapidly  disappears  on  deprivation  of  food. 
On  this  account  the  course  of  the  metabolism  during  starvation  is 
the  same  after  the  first  two  or  three  days,  whether  the  animal  has 
previously  received  large  or  small  amounts  of  protein  in  its  diet. 
In  man,  even  this  limited  power  of  storing  nitrogen  is  apparently 
absent.  Under  no  circumstances  can  we  produce  a  laying  on  of 
fat  in  the  body,  even  in  carnivora,  however  much  the  protein  income 
is  increased. 

The  metabohsm  of  fats  and  carbohydrates,  on  the  other  hand, 
is  determined,  not  by  the  amount  of  these  substances  in  the  food, 
but  by  the  energy  requirements,  i.e.  the  functional  activity  of  the 
hving  tissues.  Any  excess*  of  either  of  these  foods  simply  gives  rise 
to  their  storage  in  the  body  almost  entirely  in  the  form  of  fat.  How 
are  we  to  regard  the  particular  position  taken  up  by  the  proteins 
in  metabohsm  ?  Voit,  whose  laborious  observations  form  the 
foundation  of  all  our  present  knowledge  of  metabohsm,  drew  a  sharp 
contrast  between  the  proteins  which  were  built  up  to  form  parts  of 
the  living  cells,  the  tissue  or  niorphotic  protein,  and  those  which 
underwent  rapid  oxidation  in  the  tissue  juices  without  ever  forming 
an  integral  constituent  of  the  living  protoplasm.  The  latter  he 
designated  circulating  protein.  The  rapid  fall  in  the  nitrogenous 
excretion  during  the  first  two  days  of  starvation  he  ascribed  to  the 
using  up  of  the  circulating  protein.  As  soon  as  this  was  exhausted 
the  animal  was  reduced  to  living  on  its  own  tissues,  so  bringing  into 
the  metabolic  cycle  the  tissue-proteins  themselves.  This  theory  has 
been  energetically  attacked  of  late  years  by  Pfliiger,  according  to 
whom  the  whole  of  the  protein,  which  is  broken  down  and  oxidised 
to  urea,  must  at  one  time  have  formed  an  integral  part  of  a  living 
cell,  so  that  tissue-protein  would  be  the  sole  source  of  the  urea.    He 

*  That  is,  assuming  that  the  animal  is  able  to  digest  and  absorb  the  excess. 
On  this  factor  probably  depends  the  possibility  of  fattening  an  animal. 

718 


THE  SIGNIFICANCE  OF  THE  FOOD -STUFFS  719 

explains  the  rapid  excretion  of  nitrogen  which  follows  the  ingestion 
of  a  protein  meal  by  the  special  avidity  of  the  animal  cell  for  protein. 
When  enough  of  this  is  presented  to  it   it  feeds  upon  nothing  else, 
and  only  when  there  is  a  comparative  lack  of  protein  will  it  make 
use  of  carbohydrate  or  fat  for  its  needs.     Thus  while  a  dog  is  fed  on 
a  rich  mixed  diet  it  lives   practically  on  protein  alone,  storing  up 
the  fats  and  carbohydrates  of  the  food  as  fat.     If  food  be  now  with- 
drawn the  animal  must  live  either  at  the  expense  of  its  own   li\'ing 
tissue  (proteins)  or  must  attack  the  stored-up  fats  in  its  body.     The 
latter  alternative,   as  a  matter  of  fact,  takes  place.     The  animal 
spares  the  precious  protein  and  lives  on  the  fat  of  its  own  body. 
Hence  comes  the  gxeat  fall  in  the  excretion  of  urea  that  is  observed 
in  starvation,  the  consumption  of  proteins  sinking  to  the  indispensable 
minimum.     If  now  a  protein  meal  be  given,  the  cells  of  the  body 
return  to  their  former  way  of  hving,  and  satisfy  as  much  of  their 
needs  as  possible  at  the  expense  of  protein,  so  that  the  urea  excretion 
rises  almost  in  proportion  to  the  food  given.   In  order  to  attain  nitro- 
genous equilibrium  on  a  purely  protein  diet,  it  is  necessary  to  give 
the  cells  enough  protein  for  their  total  requirements,  i.e.  three  to  five 
times  as  much  as  would  correspond  to  the  nitrogenous  excretion  during 
hunger.  If  a  larger  amount  of  protein  be  given  than  is  necessary  for  the 
maintenance  of  nitrogenous  equihbriimi,  a  certain  amount  of  nitrogen 
is  retained  in  the  body,  probably  as  protein,  giv^ng  rise  to  an  increase 
in  the  total  living  material  of  the  body,  and  the  animal  increases 
in  weight.     The  amount  of  urea  excreted  by  an  animal  is  propor- 
tional not  only  to  the  quantity  of    protein  taken  in  with  the  food 
but  also  to  the  weight  of  the  animal ;  so  the  animal  which  has  grown 
heavier  in  consequence  of  increased  supply  of  nitrogenous  food  will 
need  a  larger  amount  of  protein  to  maintain  its  nitrogenous  equili- 
brium, which  will  be  produced  with  the  same  amount  of  protein 
as  soon  as  the  animal  has  increased  in  weight  to  a  certain  extent. 
In  order  therefore  to  maintain  the  increase  in  weight,  it  is  necessary 
to  give  ever-increasing  quantities  of  protein,  and  the  stuffing  process 
is  finally  put  an  end  to  by  the  refusal  of  the  digestive  organs  to  digest 
any  more. 

In  support  of  these  views  considerable  stress  has  been  laid  by  Pfliiger  on 
some  experiments  carried  out  in  his  laboratory  by  Schondorff.  According  to 
Voit  the  greater  excretion  of  urea  in  a  protein-fed  animal  is  due  to  the  fact 
that  there  is  an  increased  circxdation  of  a  fliiid  that  is  rich  in  proteins  round 
the  cells.  According  to  Pfliigcr's  views,  however,  the  presence  of  a  greater 
or  less  amomit  of  protein  in  the  nourishing  medium  would  not  be  the  deter- 
mining factor  for  the  amount  of  vu-ea  formed,  which  would  be  regulated  simply 
and  solely  by  the  condition  of  the  cells  themselves.  To  decide  this  point, 
defibrinatcd  dog's  blood  was  led  alternately  through  the  hind  limbs  and  the  liver 
of  another  dog,  in  order  to  get  the  products  of  metabolism  of  the  limb  tiseues 
and  then  convert  them  into  urea  by  passing  the  blood  through  the  liver. 


720  PHYSIOLOGY 

(1)  In  one  set  of  experiments  the  blood  from  a  dog  that  had  been  starved 
for  five  days  was  led  tlirough  the  organs  of  a  well-fed  dog.  In  these  experi- 
ments Schondorff  found  that,  without  exception,  the  urea  in  the  blood  was 
largelj^  increased  at  the  end  of  the  experiment. 

(2)  In  a  second  series  of  experiments  the  blood  of  a  fasting  animal  was  led 
through  the  hind  limbs  and  liver  of  a  fasting  animal.  In  these  the  amount  of 
urea  in  the  blood  was  unaltered. 

(3)  In  a  third  set  blood  of  a  well -fed  animal  was  led  through  organs  and  liver  of 
a  fasting  animal.     In  these  cases  the  amount  of  urea  was  always  diminished. 

It  was  concluded  from  these  experiments  that  the  extent  of  protein  metaboUsm 
depends  on  the  nutritive  condition  of  the  cells  and  not  on  the  protein  contained 
in  the  circulating  fluids.  It  must  be  remarked,  however,  that  the  absolute  quan- 
tities of  urea  obtained  in  these  experiments  were  minute  in  comparison  with 
those  which  would  be  formed  by  the  same  weight  of  tissues  in  the  whole  normal 
animal.  Thus  in  one  of  Schondorff 's  experiments,  the  dog,  which  was  extremely 
well  fed,  was  tm-ning  out  nitrogen  at  the  rate  of  38  grm.  a  day,  i.e.  1-5  grm. 
an  hoiu-.  In  the  same  animal  the  blood  perfused  for  four  and  a  half  hoiu-s 
through  the  hind  limbs  and  liver  picked  up  only  25  mg.  of  nitrogen  in  the 
form  of  m"ea.  During  this  time  the  whole  animal  would  have  formed  and 
excreted  6  grm.  of  nitrogen  as  urea,  i.e.  200  times  as  much  as  that  actually 
obtained.  Folin  remarks  that  25  mg.  of  nitrogen  is  not  sufficient  fovmdation 
for  so  weighty  a  superstructure  as  the  theories  which  have  been  based  on  this 
experiment. 

■  There  can  be  little  doubt,  however,  that  Voit  was  substantially- 
correct  in  assigning  a  twofold  fate  to  the  ingested  protein,  and  that, 
as  Speck  has  pointed  out,  we  can  consider  protein  metabolism  under 
two  headings,  viz.  tissue  or  nutritional  metabolism  and  energy 
metabolism.  Since  the  proteins  form  the  main  constituent  of  living 
protoplasm,  the  death  and  destruction  of  cells,  which  are  constantly 
going  on  in  the  body,  must  result  occasionally  in  the  production  of 
substances  which  are  not  available  for  resynthesis,  and  are  therefore 
turned  out  of  the  body  with  the  urine.*  A  certain  proportion  of 
the  proteins  of  the  food  must  therefore  be  apphed  to  replacing  this 
waste  of  tissue.  The  proportion  will  be  larger  in  cases  where  a 
growth  of  the  nitrogenous  tissues  is  occurring,  as  in  the  young  animal 
or  during  convalescence  from  a  wasting  disorder.  On  the  other 
hand,  a  certain  proportion  of  the  nitrogen  in  the  urine  will  be  derived 
from  the  breakdown  of  tissues,  and  this  in  its  turn  will  be  increased 
under  any  conditions  which  bring  about  an  augmented  tissue 
disintegration,  such  as  the  toxsem'a  of  fevers,  poisoning  by  arsenic 
or  phosphorus,  or  partial  asphyxia  by  deprivation  of  oxygen,  as  after 
inhalation  of  carbon  monoxide  gas.      In  this  function  protein  cannot 

*  Tigerstedt  suggests  that  the  irreducible  minimal  protein  consumption 
may  be  due,  not  to  a  special  metaboUc  cycle  of  the  protein  on  its  way  into  and 
out  of  the  living  cell,  but  to  the  fact  that  the  circulating  fluids  of  the  body 
contain  large  amounts  of  protein  as  essential  and  constant  ingredients,  and 
the  living  cells  therefore,  which  are  bathed  by  these  fluids,  cannot  refrain, 
even  in  times  of  protein  scarcity,  from  feeding  to  a  certain  extent  on  these 
the  predominant  constituents  of  their  nutrient  medium. 


THE  SIGNIFIC^ANCE  OF  THE  FOOD-STUFFS  721 

be  replaced  by  either  of  tlie  other  food-stuffs.  With  regard  to  its 
second  fate,  viz.  the  furnishing  of  energy  to  the  body,  protein  stands 
on  the  same  level  as  carbohydrates  or  fats,  its  relative  v^ue  as 
compared  with  these  two  classes  of  substances  being  represented 
by  its  physiological  heat-value.  Owing  to  the  inability  of  the  body 
to  store  protein  to  any  marked  extent,  any  protein  which  is  absorbed 
in  the  aUnientary  canal  in  excess  of  the  nutritional  requirements  of 
the  body  is  at  once  broken  down  and  oxidised  to  satisfy  the  energy 
requirements  of  the  cells.  The  NH  and  NHg  groups  in  the  protein 
molecule  add  little  or  nothing  to  its  chemical  or  potential  value. 
The  energy  value  of  the  protein  depends  on  its  carbon  and  hydrogen 
content,  and  it  seems  probable  that  the  greater  part  of  the  nitrogen 
is  split  off  as  ammonia  from  the  protein  molecule  during  or  shortly 
after  its  absorption  from  the  ahmentary  canal.  It  is  on  this  account 
that  an  increased  excretion  of  urea  is  the  almost  immediate  con- 
sequence of  the  ingestion  of  protein.  The  point  made  by  Pfliiger 
against  Voit,  viz.  that  no  oxidation  occurs  in  the  lymph  or  blood, 
is  really  beside  the  mark.  The  living  cell  is  a  complex  system  which 
may  include  food  in  all  degrees  of  oxidation  or  chemical  change, 
without  this  food  material  necessarily  forming  part  of  the  living 
framework.  Every  histologist  distinguishes  the  paraplasma  from 
the  more  active  and  essential  protoplasm,  and  we  must  assume 
that  it  is  in  the  ultra-microscopic  interstices  of  the  foam-like 
protoplasm  that  the  chief  processes  of  chemical  change  and  oxidation 
occur.  A  proof  therefore  that  oxidation  depends  on  the  condition  of 
the  cells  and  not  on  that  of  the  blood  does  not  justify  the  conclusion 
that  the  whole  nitrogenous  metabolism  of  the  body  is  confined  to 
the  living  protoplasm  itself. 

FoUn  has  lately  brought  forward  a  number  of  facts  which  point 
not  only  to  a  twofold  origin  of  the  nitrogen  of  the  urine  but  also 
to  a  qualitative  difference  in  the  two  orders  of  protein  metabohsm. 
Whereas  in  the  urine  of  man  on  a  normal  diet  the  urea  nitrogen 
forms  85  per  cent,  or  more  of  the  total  nitrogen,  a  reduction  of  the 
protein  ration  to  the  minimum  necessary  to  meet  the  nutritional 
requirements  of  the  body  causes  not  only  an  absolute  diminution 
of  the  urea  but  a  large  relative  diminution  when  compared  with  the 
other  constituents  of  the  urine,  such  as  creatinin.  He  concludes 
therefore  that  the  nitrogenous  end-products  of  nutritional  meta- 
bohsm are  different  from  those  of  the  energy  metabolism.  As 
Speck  has  pointed  out,  there  is  also  a  difference  in  the  time-relations 
of  the  two  orders  of  metabolism.  Whereas  the  nitrogen,  which 
furnishes  no  energy  to  the  body,  is  rapidly  eliminated  when  protein 
is  being  utihsed  for  the  supply  of  energy  to  the  body,  the  occurrence 
of   increased  tissue  waste  causes   a   rise   of   nitrogenous   excretion, 

46 


722  PHYSIOLOGY 

which  comes  on  slowly,  often  after  the  lapse  of  a  day.  and  may  last 
two  or  three  days.  The  process  of  protoplasmic  disintegration 
appears  therefore  to  occur  in  a  series  of  stages,  which  occupy  a  con- 
siderable time  and  end  in  the  production  of  substances  ciualitatively 
distinct  from  that  substance,  urea,  which  is  the  almost  exclusive 
nitrogenous  end-product  of  the  energy  metabolism  of  protein. 

THE  FOOD-VALUE   OF  CERTAIN  SUBSTANCES   ALLIED 
TO   PROTEINS 

PROTEOSES  AND  PEPTONES.  In  the  digestion  of  the  naturally 
occurring  proteins  the  first  products  of  hydration  consist  of  a  mixture 
of  substances  known  as  proteoses  and  peptones.  In  the  further 
processes  of  digestion,  under  the  influence  of  the  ferments  of  the 
pancreas  and  small  intestine,  these  substances  are  converted  into 
the  amino-acids  which  we  have  learnt  to  regard  as  the  proximate 
constituents  of  the  protein  molecule.  Many  experiments  have  been 
performed  in  order  to  determine  the  nutritive  value  of  these  digestive 
products.  In  nearly  all  cases  it  has  been  found  that  the  meat  in 
the  diet  of  an  animal  can  be  replaced  by  a  corresponding  quantity 
of  the  products  of  digestion  of  the  same  meat  without  interfering 
with  the  nitrogenous  equilibrium  of  the  animal,  and  Loewi  and  others 
have  shown  that  the  same  result  may  be  attained  by  feeding  an 
animal  on  the  products  of  pancreatic  digestion  of  protein,  i.e.  a 
mixture  consisting  almost  entirely  of  amino-acids.  Since  the  proteins 
of  the  body  differ  in  their  composition  from  the  majority  of  the 
proteins  of  the  food,  it  is  evident  that  each  food-protein  molecule 
has  to  be  taken  to  pieces  and  reconstructed  before  it  can  take  its 
place  in  the  body  fabric,  and  it  is  therefore  only  natural  that,  so  far 
as  metabolism  is  concerned,  the  results  should  be  identical  whether 
we  feed  the  animal  w^th  the  ordinary  food-protein  or  with  the  products 
of  its  metabolism.  This  mode  of  feeding  cannot,  however,  be  regarded 
as  presenting  any  advantages.  Under  normal  circumstances  the 
food  molecules  are  broken  down  by  degrees.  Their  products  of 
hydrolysis  are  set  free  in  small  quantities  at  a  time  and  can  be 
therefore  absorbed  and  disposed  of  in  proportion  as  they  are  set  free. 
On  the  other  hand,  a  sudden  flooding  of  the  ahmentary  canal  with 
a  large  quantity  of  the  products  of  diges'tion  introduces  an  abnormal 
factor  which  must  tend  to  produce  wastage  of  nitrogen  in  the  body 
and  to  disturb  the  normal  chain  of  processes  involved  in  the  regular 
course  of  digestion. 

COLLAGEN  AND  GELATIN.  Among  the  various  sclero-proteins 
or  albuminoids  which  occur  as  normal  constituents  of  our  foods 
these  two  are  the  only  substances  which  undergo  digestion  and  solution 
in  the  ahmentary  canal  to  any  appreciable  extent,  other  substances, 


THE  SIGNIFICA^fCE  OF  THE  FOOD-STUFFS  723 

sucli  as  elastin  and  keratin,  reappearin<i  for  the  greater  part  in  the 
faeces.  As  we  have  seen,  gelatin,  the  first  product  of  hydration  of 
collagen,  represents,  so  to  speak,  an  imperfect  protein.  When  it  is 
hydrolysed  by  acids  its  disintegration  products  include  the  ordinary 
amino-acids  of  the  fatty  series,  including  a  considerable  amount 
of  glycine  and  also  a  certain  amount  of  phenyl  alanine  and  proline. 
The  oxy-phenyl  group  which  occurs  in  all  the  food-proteins  in  the  form 
of  tyrosine,  as  well  as  the  indol-containing  group  tryptophane,  are 
absent.  On  this  account  gelatin  does  not  give  either  Millon's 
test  or  the  Hopkins-Adanikiewicz  test  with  glyoxylic  acid.  As 
might  be  expected  from  its  composition,  gelatin  cannot  entirely 
replace  the  proteins  of  the  food,  but  is  able  to  take  the  place 
of  part  of  the  proteins.  If  nitrogenous  equilibrium  has  been 
attained  on  a  certain  amount  of  protein  together  with  a  mixed 
diet,  a  considerable  proportion  of  the  protein,  but  not  all,  can 
be  replaced  by  gelatin.  In  an  experiment  on  a  dog,  in  nitro- 
genous equiUbrium  on  a  mixed  diet  containing  0'(i  grm.  protein 
per  kilo,  it  was  found  that  fully  five-sixths  of  the  protein  could  be 
replaced  by  gelatin  without  any  disturbance  of  the  nitrogenous 
metabolism.  Physiologists  have  succeeded  in  maintaining  animals 
for  a  short  time  in  a  state  of  nitrogenous  equilibrium  on  a  diet  con- 
taining no  protein,  but  in  its  place  a  mixture  of  gelatin  with  tyrosine 
and  tryptophane.  It  is  doubtful,  however,  whether  such  experi- 
ments could  be  continued  indefinitely.  In  most  cases  the  animal 
after  a  time  refuses  to  eat  the  gelatin.  A  somewhat  similar  behaviour 
is  found  in  the  case  of  zein,  the  crystallised  pro'tein  from  maize,  which 
yields  no  tryptophane  or  tyrosine  on  hydrolysis.  Hopkins  has  shown 
that  animals  fed  with  zein,  together  with  a  small  proportion  of 
tryptophane,  live  longer  than  those  fed  wuth  zein  alone.  But  in  no 
case  could  he  maintain  life  on  this  diet  for  a  period  greater  than 
forty-five  days.  There  are  evidently  other  groups  in  the  protein 
molecule  which  are  essential  for  the  maintenance  of  life  and  which  were 
not  represented  in  the  mixture  of  zein  and  tryptophane. 

Experiments  have  been  carried  out  in  order  to  ascertain  whether  asparagine, 
which  forms  so  important  a  nitrogenous  constituent  of  young  plants,  can  be 
directly  utilised  by  animals.  There  is  evidence  that  this  substance  has  a  real 
nutritive  value  for  certain  herbivora.  The  utilisation  is  not,  however,  a  direct 
one.  The  asparagine  appears  to  be  taken  up  by  the  bacteria  which  swarm  in 
the  paunch  or  caieum  of  these  animals.  It  is  built  up  by  these  micro-organisms 
into  protein,  and  it  is  the  protein  of  the  micro-organisms  and  not  the  asparagine 
itself  which  is  digested,  absorbed,  and  utilisi-d  by  the  mammal. 

OTHER  CONSTITUENTS  OF   THE   FOOD 
CELLULOSE.     This    substance,  which    forms    the    cell    walls    of 
plants,  furnishes  an  important  food-supply  to  the  herbivora.      Its 


724  PHYSIOLOGY 

digestion  is  not,  however,  carried  out  by  the  action  of  juices  secreted 
by  the  intestinal  canal  itself.  The  solution  of  the  cellulose  is  effected 
partly  under  the  influence  of  a  cellulase  or  cytase  present  in  the 
plant  cells  themselves,  partly  under  the  influence  of  the  micro- 
organisms living  in  the  paunch  or  csecuni.  Under  the  influence  of 
these  bacteria  cellulose  is  dissolved  with  the  production  of  carbon 
dioxide,  methane,  and  butyric  and  acetic  acids.  In  man  the  greater 
part  of  the  cellulose  of  the  food  is  undigested,  and  its  chief  value 
appears  to  be  that  of  lending  bulk  to  the  indigestible  material  and 
so  aiding  the  normal  movements  of  the  intestines.  In  the  case  of 
young  plant  cells,  such  as  those  of  lettuce  or  carrots,  a  certain  per- 
centage of  the  cellulose  undergoes  solution  in  the  intestine.  Here, 
again,  the  digestion  is  probably  effected  by  the  agency  of  putrefactive 
organisms. 

ALCOHOL.  When  alcohol  is  taken  by  man  in  moderate  quantities 
the  greater  part  of  it  undergoes  oxidation,  and  leaves  the  body  as 
carbon  dioxide  and  water.  About  10  per  cent,  which  escapes  oxida- 
tion is  excreted  unaltered  by  the  lungs  and  urine.  This  oxidation 
of  alcohol  is  a  result  of  true  utilisation,  since  the  addition  of  a  certain 
amount  of  alcohol  to  the  food  does  not  result  in  an  increase  of  the 
output  of  carbon  dioxide.  In  small  quantities  therefore  alcohol 
can  act  as  a  food.  This  function,  however,  is  quite  unimportant, 
and  is  overshadowed  by  the  poisonous  action  of  this  substance.  A 
man  unaccustomed  to  its  action  cannot  take  more  than  16  to  25  grm. 
without  experiencing  its  poisonous  effects.  This  amount  of  alcohol 
only  represents  a  total  heat-value  of  112  to  175  calories,  i.e.  only 
about  5  per  cent,  of  the  total  energy  requirements  of  the  body. 
Only  very  rarely  therefore  can  we  be  justified  in  administering  alcohol 
as  a  food.  Its  value  in  a  diet  is  entirely  that  of  an  accessory  or 
adjuvant  in  exciting  appetite  by  its  taste  and  smell,  an  advantage 
which  is  largely  counterbalanced  by  the  danger  of  introducing  a 
poison  into  the  body  which  on  long  continuance  tends  to  set  up 
various  degenerative  changes  in  the  tissues,  and  if  taken  in  any 
quantity  at  one  time  causes  a  temporary  abolition  of  those  processes 
of  inhibition  and  control  which  have  been  the  determining  factors 
in  the  survival  of  the  race  throughout  the  struggle  for  existence. 

THE  INORGANIC  FOOD-STUFFS 
If  an  animal  be  fed  with  the  proper  quantities  of  fats,  proteins, 
and  carbohydrates,  from  which  all  the  salts  have  been  removed 
as  completely  as  possible,  it  rapidly  shows  a  distaste  for  the  food, 
becomes  ill,  and  dies  in  a  shorter  time  than  if  it  were  receiving  no 
food  at  all.  Part  of  the  symptoms  which  occur  in  these  cases  are 
due  to  the  production  of  acid  substances,  e.g.  sulphuric  acid,  in  the 


THE  SIGNIFICANCE  OF  THE  FOOD-STUFFS         725 

course  of  metabolism  of  the  proteins.  It  is  possible  to  obviate  this 
acid  intoxication  by  administering  sodium  carbonate  with  the  food. 
This  admixture,  however,  only  suffices  to  prolong  the  life  of  the 
animal  for  a  short  time.  It  is  evident  therefore  that  the  inorganic 
constituents  of  the  food,  although  yielding  no  energy  to  the  body, 
are  as  essential  for  the  maintenance  of  life  as  the  energy-yielding 
food-stufEs,  namely,  proteins,  carbohydrates,  and  fats.  In  the  course 
of  this  work  we  shall  have  occasion  to  study  the  intimate  dependence 
of  the  functions  of  various  tissues,  such  as  skeletal  and  heart  muscle, 
on  the  presence  of  salts  in  normal  proportions  in  the  fluids  with 
which  they  are  bathed.  Animals  in  a  state  of  salt  hunger  show 
by  the  disorders  of  digestion  which  occur  that  the  presence  of  salts 
is  equally  requisite  for  the  due  performance  of  the  processes  of 
secretion  and  absorption.  Towards  the  end  of  the  experiment  the 
animal  vomits  its  food,  which  shows  no  signs  of  digestion  even 
when  it  has  lain  some  hours  in  the  stomach.  Forster  has  shown 
that  in  salt-hunger  the  body  is  continually  giving  off  inorganic  con- 
stituents in  the  urine.  The  amount  of  these  is  smallest  when  it  is 
supphed  richly  with  organic  food-stufis.  It  seems  that  the  salts 
of  the  body  exist  in  a  state  of  unstable  combination  with  the  tissue 
constituents,  especially  the  proteins.  If  the  amount  of  food  supplied 
is  insufficient,  the  animal  lives  on  its  o^vn  tissues,  thus  setting  free 
salts  which  appear  in  the  urine.  The  loss  of  salts  to  the  body  will 
therefore  be  in  direct  proportion  to  the  degree  in  which  the  animal  is 
living  at  the  expense  of  its  own  tissues. 


SECTION  VI 

THE  NORMAL  DIET  OF  MAN 

The  adult  man  has  to  take  a  certain  quantity  of  food  every  day 
in  order  to  furnish  an  amount  of  energy  equal  to  that  lost  from  the 
body  as  heat  and  mechanical  work,  and  to  replace  the  waste  of  tissue. 
This  income  is  represented,  not  by  the  total  food  taken  into  the 
alimentary  canal,  but  by  the  proportion  of  the  food  which  is  absorbed 
from  the  canal.  This  will  vary  with  the  dic^estibility  and  nature  of 
the  diet,  and  in  any  experiments  instituted  to  determine  the  metabolism 
of  man  the  first  question  that  must  be  decided  is  as  to  the  proportion 
of  food-3tuffs  actually  utilised.  Food  which  is  not  absorbed  will  be 
excreted  from  the  body  in  the  faeces.  The  degree  of  utilisation  of 
food-stuffs  will  therefore  be  given  by  an  analysis  of  the  faeces  passed 
daily  on  any  given  diet.  In  order  to  be  certain  that  the  faeces  passed 
during  a  given  time  correspond  to  and  are  derived  from  the  food  taken 
in  at  the  same  time,  it  is  usual  to  give  at  the  beginning  and  end  of  the 
experiment  a  capsule  of  lampblack,  so  as  to  colour  the  faeces  and 
delimit  those  formed  during  the  period  of  the  experiment.  The  faeces 
during  starvation  contain  a  certain  proportion  of  nitrogen,  carbo- 
hydrates, and  fats,  and  in  judging  of  the  degree  of  utilisation  of  any 
given  food-stuff  the  amounts  of  these  substances  excreted  by  the 
alimentary  canal  during  starvation  must  be  deducted  from  the  total 
amount  found  in  the  faeses. 

The  excretion  of  nitrogen  by  the  intestines  varies  between  0"54 
and  1"36  grm.  per  day.  If  we  find  an  amount  of  nitrogen  in  the 
faeces  not  exceeding  these  figures,  we  are  justified  in  concluding 
that  the  utilisation  of  the  nitrogenous  constituents  of  the  food  is 
practically  complete.  This  is  the  case  when  the  man  receives  as 
food  the  animal  proteins,  such  as  meat,  eggs,  or  milk.  In  experiments 
carried  out  with  these  materials  the  amount  of  nitrogen  of  the  faeces 
varied  between  0"14  and  I'd  grm.  Only  when  excessive  amounts  of 
milk  are  given  is  the  utilisation  less  complete  and  the  nitrogen  in 
the  faeces  increased  above  this  amount.  If,  however,  the  protein 
be  given  in  the  form  of  vegetable  food,  the  wastage  of  nitrogen  by 
the  faeces  is  much  greater.  It  may  rise  as  high  as  48  per  cent,  and 
amount  to  9  grm.  per  day.  Nearly  always  it  exceeds  15  per  cent. 
This  greater  wastage  of  the  nitrogen  of  vegetable  food  depends  partly 

726 


THE  NORMAL  DIET  OF  MAN  727 

on  the  fact  that  certain  non-protein  and  indigestible  nitrogenous 
constituents  of  seeds  and  grains  are  reckoned  as  protein,  partly  on 
the  fact  that  a  considerable  proportion  of  the  protein  may  be  enclosed 
in  indigestible  envelopes,  and  partly  on  the  greater  stimulant  action 
of  the  vegetable  diet  on  the  movements  of  the  alimentary  canal, 
so  that  the  food  is  hurried  through  the  intestine  before  the  processes 
of  digestion  and  absorption  have  had  time  to  attain  their  limit.  This 
last  factor  may  interfere  also  with  the  digestion  of  animal  protein 
on  a  mixed  diet.  The  fats  and  carbohydrates  of  the  ordinary  diet 
of  man  are  also  utilised  to  a  very  large  extent.  The  faeces  passed 
on  a  fat-free  diet  always  contain  between  3  and  6  grm.  of  ethereal 
extract  which  is  reckoned  as  fat.  When  the  fat  of  the  food  consists 
largely  of  olein  and  is  fluid  at  the  temperature  of  the  body,  it  is 
almost  totally  absorbed,  the  absorption  becoming  less  as  the  melting- 
-point of  the  fat  rises.  Ordinary  carbohydrates  are  also  very  well 
absorbed,  but  here  very  large  variations  may  be  produced  by  altering 
the  condition  in  which  they  are  presented  in  the  food.  The  following 
table  shows  the  relative  digestibility  of  the  different  food-stuffs  in  a 
healthy  individual  on  a  normal  diet  : 

Percentage  of  Food-stuff  Absorbed 

Protein  Fat      Carbohydrate      Ash     Total  energy 

Average      of   five  [  g,.g  ^^  g_;_  __.^  ^^^ 

expenments         I 

In  judging  therefore  of  the  sufficiency  of  any  given  dietary, 
it  is  important  to  remember  that  on  the  average  only  about  90  per 
cent,  of  the  total  energy  of  the  food  is  available  for  use  by  the 
body.  If,  for  instance,  the  body  requires  an  amount  of  energy 
equivalent  to  3000  calories  per  day,  it  would  be  necessary  to  give 
food  corresponding  to  3333  calories  per  day.  If,  as  is  the  case 
with  the  poorer  classes,  the  food  consists  mainly  of  vegetable 
products  it  may  be  necessary  to  increase  still  further  this  allow- 
ance, since  on  a  diet  such  as  rye  bread  the  loss  of  energy  in  the 
faeces  may  amount  to  as  much  as  35  per  cent,  of  the  total  energy 
of  the  food. 

The  quantity  of  food  which  is  necessary  to  keep  an  adult  man 
in  a  state  of  health,  without  loss  or  gain  of  weight,  is  represented 
by  that  amount  which  is  sufficient  after  absorption  to  supply  the 
total  daily  output  of  energy.  This  output  will  vary  considerably  not 
only  from  individual  to  individual  but  also  with  the  weight  and 
size  of  the  man,  and  above  all  with  his  state  of  muscular  activity. 
Thus  in  the  case  of  a  woman  weighing  4^t4~)  kilo.s,  in  a  state  of 
hysterical  sleep,  the  total  output  of  energy  during  twenty-four  hours 
amounted   to    1228  calories,  i.e.  248  calories  per  kilo  body  weight. 


728 


PHYSIOLOGY 


Under  more  normal  conditions,  with  the  increased  tone  of  muscle 
which  is  present  during  waking  hours,  the  evolution  of  energy  by 
the  body  is  increased  above  this  amount.  Pettenkofer  and  Voit 
found  that  a  resting  individual  had  an  output  of  2300  calories  during 
starvation  and  2670  calories  on  a  normal  diet.  A  series  of  experi- 
ments by  Tigerstedt  on  individuals  kept  in  a  state  of  rest,  but  on 
normal  diet,  gave  results  varying  between  26  and  36  calories  per  kilo  for 
the  twenty-four  hours.  We  may  take  therefore  30  calories  per  kilo  body 
weight  as  the  average  requirements  of  a  man  in  a  state  of  rest.  This 
would  correspond  to  2100  calories  for  a  man  weighing  70  kilos.  When 
muscular  work  is  performed  the  energy  output  is  at  once  largely 
increased,  and  with  it  the  food  requirements  of  the  body.  The 
attempts  which  have  been  made  to  arrive  at  some  idea  of  the  average 
amounts  of  food  required  by  a  working  man  have  been  based  not 
so  much  on  scientific  experiment  as  on  an  analysis  and  comparison 
of  the  diets  in  general  use  among  different  classes  of  men,  the  amounts 
of  which  are  determined  by  the  instinct  of  the  man  himself,  while 
its  quality  is  limited  by  his  daily  earnings.  Tigerstedt  divided  the 
different  diets  which  have  been  investigated  into  six  classes,  according 
to  the  total  amount  of  energy  which  each  of  them  represents.  These 
are  as  follows  : 


Group 

Protein 

Pat 

Carbo- 
hydrate 

Calories 
gross 

Calories 
net 

Calories  per 

kilo  body 

weight 

I 

II  . 

III  . 

IV  . 

V  . 

VI  . 

84 

88 
130 
141 
167 
152 

56 
39 
64 
71 
89 
139 

599 
512 
520 
677 

774 
1062 

2483 
2825 
3257 
4020 
4685 
6269 

2235 
2538 
2932 
3618 
4218 
5642 

32 
36 
42 
52 
60 
81 

In  view  of  this  great  variation  among  the  diets  of  different 
individuals  it  becomes  difficult  to  arrive  at  any  conclusion  as  to  the 
diet  which  should  be  regarded  as  the  average  and  should  guide  us 
in  drawing  up  dietary  scales  for  public  institutions.  Voit,  from 
experiments  on  ordinary  workmen  performing  eight  or  nine  hours' 
labour  a  day,  such  as  a  bricklayer  or  carpenter,  has  laid  down  the 
following  as  an  average  diet,  namely  : 


Protein 
Fat  . 
Carbohydrate 


118  grm. 
56      „ 
500      „ 


THE  NORMAL  DIET  OF  MAN  729 

This  would  correspond  to  a  total  calorie  value  of  3055,  or,  sub- 
tracting 10  per  cent,  for  the  food  which  is  not  utilised  in  the  alimentary 
canal,  to  2749  calories.  The  fat  in  this  diet  is  rather  low,  preference 
being  given  to  the  carbohydrate  on  account  of  its  greater  cheapness. 
It  is  not  advisable  to  reduce  the  fat  below  this  limit,  since  the 
human  body  has  a  need  for  a  certain  proportion  of  fat,  in  the  absence  of 
which  the  utilisation  of  the  other  food-stuffs  does  not  proceed  normally. 
The  presence  of  fat  in  the  diet  is  especially  important  in  the  case  of 
infants  and  young  children,  many  of  the  disorders  of  nutrition  pre- 
.  valent  among  the  children  of  the  lower  classes  being  largely  determined 
by  the  absence  of  the  proper  quantity  of  fat  from  the  diet.  In  the 
case  of  severe  work  this  diet  may  not  be  adequate  to  supply  the 
necessary  quantity  of  energy.  Thus,  for  soldiers,  Voit's  ration  during 
manoeuvres  consists  of  : 

Protein 135  grm. 

Fat 80      „ 

Carbohydrate         ....     500      ,, 

with    a   total    calorie     value    of    3348.       His    ration   for    war-time 
consists   of  : 

Protein 145  grmj 

Fat 100      „ 

Carbohydrate        ....     500      ,, 

corresponding  to  3575  calories.  Even  this  may  be  insufficient  to 
supply  the  energy  needs  during  a  period  of  intense  muscular  activity. 
In  one  experiment  by  Atwater,  in  which  the  individual  performed 
muscular  work  for  a  period  of  sixteen  hours  out  of  the  twenty- 
four  in  a  calorimeter,  the  total  energy  given  out  amounted  to 
over  9000  calories  in  the  course  of  the  twenty-four  hours.  It  is 
probable,  however,  that  in  all  cases  where  such  excessive  calls  on 
the  energies  of  an  individual  are  made,  one  or  even  two  rest  days 
would  follow  the  day  of  exertion,  so  that  the  deficiency  of  the  food 
on  the  day  of  exertion  would  be  made  good  by  an  increased  intake 
of  food  on  the  following  days.  Thus  three  days'  intake  of  5000 
calories  would  yield  sufficient  energy  for  the  output  of  9000  calories 
on  one  day  of  exertion  and  of  3000  calories,  the  normal  amount, 
on  each  of  the  two  succeeding  rest  days.  The  relative  part  played 
by  the  different  constituents  of  a  diet  in  yielding  energy  to  the 
body  has  been  determined  by  many  observers  and  especially  in 
a  long  series  of  researches  l)y  Atwater.  On  tlie  next  page  are  given 
details  of  the  daily  food  in  (tno  snrh  oxporiment  on  a  man  weighing 
70  kilos. 


730 


PHYSIOLOGY 


Food           ,  Weight 

material       ^^'"'"^^ 
grm. 

Water 
grm. 

Protein 
grm. 

Fat 
grm. 

Carbo- 
hydrate 
grm. 

grm. 

c. 

gnii. 

H. 

gnu. 

Heat 
of  com- 
b>istion 
calories 

Beef           .          35 

220 

11-5 

1-0 

_ 

1-84 

6-73 

0-99 

76 

Butter       .        245 

27-2 

2-9 

208-3 

• — 

0-47 

1-54 

25-28 

1929 

Bread        .        350 

148-7 

28-3 

3-9 

165-5 

4-97 

90-69 

13-55 

913 

Gingersnaps        60 

2-4 

3-6 

3-4 

49-2 

0-63 

25-74 

3-98 

259 

Shredded 

wheat    .          40 

2-5 

4-1 

0-6 

32-2 

0-72 

16-70 

2-54 

164 

Sugar         .          60 

— 

— 

— 

60-0 

— 

25-26 

3-89 

238 

Cereal  coffee    1200 

1191-6 

0-7 

— 

7-2 

0-12 

3-96 

0-60 

41 

Whole  milk     1355 

11490 

52.9 

74-6 

69-2 

8-40 

108-00 

16-93 

1247 

Total  ration  ) 
per  day      ( 

i 

2543-4 

104-0 

291-8 

383-3 

17-15 

431-08 

67-76 

4867 

Very  few  accurate  experiments  have  been  made  on  the  daily 
requirements  of  women.  Since  the  average  weight  of  a  woman  is 
less  than  that  of  a  man  and  the  amount  of  work  performed  less  severe, 
she  will  require  a  smaller  amount  of  food  both  to  meet  the  energy 
expenditure  of  the  body  and  to  provide  for  the  repair  of  her 
tissues.  Voit,  under  the  assumption  that  the  body  weight  of  woman 
is  four-fifths  that  of  man,  and  that  her  energy  requirements  are 
diminished  in  the  same  proportion,  has  given  the  following  as  the 
daily  requirements  of  a  woman  engaged  in  manual  labour  : 

Protein         .....       94  grm. 

Fat      .  .  .         .  .  .       45      „ 

Carbohydrate        ....     400      ,, 

equivalent  to  a  gross  calorie  value  of  2444. 


RELATIVE  PROPORTIONS  OF  THE  DIFFERENT  FOOD- 
STUFFS IN  THE  DIET  OF  MAN 
Since  we  have  exact  determinations  at  our  disposal  of  the  total 
energy  output  of  a  man  under  various  conditions,  it  is  easy  to  assign 
a  total  diet  to  each  class  which  shall  satisfy  these  energy  require- 
ments. In  such  a  diet  fat  and  carbohydrate  are  mutually  replaceable 
in  proportion  to  their  calorie  value,  though  it  seems  that  in  most 
individuals  for  the  conservation  of  perfect  health  a  certain  minimum 
amount  both  of  fats  and  carbohydrates  is  necessary.  Some  observers, 
however,  have  described  an  increased  outjnit  of  carbon  dioxide  as 
the  result  of  the  ingestion  both  of  carbohydrates  and  of  fats,  pointing 
to  a  stimulating  effect  on  metabolism  of  these  food-stuffs  themselves. 
If  these  results  are  generally  applicable,  wc  cannot  regard  the  total 


THE  NORMAL  DIET  OF  MAN  731 

energy  output  of  a  man  on  a  given  diet  as  affording  a  criterion  of 
the  amount  of  food  necessary  for  him  per  day,  since  it  is  possible  tliat 
with  a  smaller  amount  of  food  the  stimulating  effect  on  metabolism 
might  be  wanting  and  that  the  functions  of  the  body  might  be 
normally  performed  with  a  greater  economy  of  material.  The  stimu- 
lating effect  of  fats  and  carbohydrates  on  metabolism  has  not,  how- 
ever, been  universally  observed,  whereas  in  the  case  of  proteins  every 
worker  has  noted  an  increased  metabolism  in  proportion  to  the 
amount  of  protein  in  the  diet.  Especially  is  this  marked  in 
man,  where  the  power  of  storing  protein  in  the  body  seems 
to  be  minimal  or  absent  in  the  normal  adult.  As  we  have  seen, 
the  protein  taken  in  the  food  has  a  twofold  destiny.  Part  of  it, 
probably  the  smaller  portion,  is  needed  to  be  built  up  into  the  tissues, 
and  to  form  living  protoplasm  in  replacement  of  wear  and  tear. 
The  other,  the  larger  portion,  serves,  like  the  fats  and  carbohydrates, 
for  meeting  the  energy  requirements  of  the  body.  The  amino- 
acids  produced  by  the  disintegration  of  the  proteins  in  the  alimentary 
canal  are  rapidly  absorbed  and  apparently  undergo  deamination 
in  the  wall  of  the  gut  itself  as  well  as  in  the  liver.  The  nitrogen 
so  split  off  is  at  once  excreted  in  the  urine,  while  the  non-nitrogenous 
moiety  is  rapidly  oxidised  to  carbon  dioxide  and  water.  How^ever 
much  protein  is  ingested,  so  long  as  the  digestive  powers  of  the 
animal  are  not  overtaxed,  all  that  is  not  required  for  replacing 
tissue  waste  undergoes  this  fate,  and  we  can  therefore  attain  nitro- 
genous equilibrium  on  a  diet  containing  50grm.  or  150  grm.  of  protein 
daily.  The  amount  of  protein  taken  in  the  food,  and  digested 
and  oxidised  in  the  body  by  any  given  individual,  affords  no  clue 
to  the  amount  which  is  absolutely  necessary  for  the  maintenance 
of  life  and  for  the  normal  discharge  of  the  bodily  functions.  It 
is  therefore  not  surprising  to  find  the  greatest  possible  divergences 
between  various  classes  of  men  in  the  quantity  of  protein  taken  in 
their  daily  food.  An  average  individual  in  affluent  circumstances, 
eating  three  meat  meals  a  day,  probably  takes  in  from  100  to 
1()0  grm.  of  protein  daily,  corresponding  to  a  nitrogen  content  of 
16  to  25  grm.  On  the  other  hand,  there  is  no  doubt  that  an  individual 
can  lead  a  perfectly  normal  existence  with  a  nitrogen  intake  as  low 
as  5  or  G  grm.  a  day.  It  is  not  possible  to  explain  these  differences 
as  determined  by  individual  idiosyncrasies,  nor  is  the  appetite  of 
the  individual  to  be  taken  as  a  safe  guide  to  the  relative  composition 
of  the  foods.  The  average  diet  of  any  race  luis  been  determined 
up  to  the  j)resent  not  so  much  by  the  })hysiological  requirements 
of  tlie  l)ody  as  by  tlie  nature  of  the  food  available.  Hence,  whereas 
the  races  living  in  tropical  climates  are  mainly  herbivorous  or  frugi- 
vorous,  the  northerners,  who  liave   (h^vclopcil   their   intt'ilcchial   and 


732  PHYSIOLOGY 

bodily  superiority  in  their  harder  struggle  for  food  amidst  more 
inclement  surroundings,  have  been  perforce  obliged  to  satisfy  their 
energy  requirements  at  the  expense  of  animal  food.  In  these  days 
when  the  products  of  all  climes  are  at  the  disposal  of  civilised  man, 
his  food-supply  is  no  longer  dependent  on  the  country  in  which  he 
lives,  and  it  is  possible  to  regulate  the  composition  of  his  food  according 
to  the  results  of  physiological  experience.  Since  the  proteins  repre- 
sent the  most  costly  constituents  of  the  food,  it  becomes  important  to 
inquire  how  much  of  this  class  of  food-stuffs  is  essential  to  the  main- 
tenance of  health  and  whether  any  advantage  is  given  by  taking 
proteins  in  excess  of  the  physiological  minimum.  The  fact  that 
those  nations  which  hold  the  highest  place  in  the  world  are  mainly 
flesh-eaters  cannot  be  regarded  as  any  proof  of  the  advantage  of  a 
flesh  diet  over  a  diet  poorer  in  protein.  It  is  the  hard  struggle  for 
existence  which  in  the  northern  races  has  eliminated  the  weakling 
and  resulted  in  the  production  of  a  superior  race.  The  fact  that 
he  is  a  flesh-eater  can  also  be  ascribed  to  the  exigencies  of  climate 
and  does  not  necessarily  prove  that  a  large  flesh  diet  is  responsible 
for  his  greater  efficiency. 

Of  late  years  a  number  of  careful  experiments  have  been  made 
to  determine  the  minimum  amount  of  protein  which  must  be  present 
in  the  daily  ration  of  man.  I  have  mentioned  above  two  experiments 
in  which  nitrogenous  equilibrium  was  obtained  with  much  smaller 
amounts  of  protein  than  those  given  in  the  normal  diets.  In  these 
experiments,  in  one  of  which  the  man  received  43*5  grm.  of  protein 
daily,  and  in  the  other  only  33  grm.  of  protein,  it  was  found  necessary 
to  give  at  the  same  time  amounts  of  carbohydrates  and  fats  far 
exceeding  those  in  the  normal  diet,  so  that  whereas,  e.g.  the  normal 
individual  takes  in  between  32  and  35  calories  per  kilo,  the  man 
on  43'5  grm.  of  protein  needed  47'5  calories  per  kilo,  and  the  one  on 
33  grm.  of  protein  needed  the  huge  amount  of  78'5  calories  per  kilo. 

Other  experimenters  have,  however,  succeeeded  in  maintaining 
perfect  health  and  nitrogenous  equilibrium  for  a  considerable  time 
on  a  diet  containing  a  much  smaller  amount  of  protein  than  has 
been  generally  considered  necessary  without  adding  to  the  ration 
abnormal  quantities  of  fats  or  carbohydrates.  Thus  Siven,  in  an 
experiment  on  himself,  found  that  he  could  maintain  nitrogenous 
equiUbrium  for  thirty-two  days  on  a  diet  containing  only  6"26  grm. 
of  nitrogen.  The  total  heat-value  of  the  food  per  day  was  only  2444 
calories.  Folin,  in  individuals  with  an  insufficient  amount  of  protein 
containing  only  2-1  to  2-4  grm.  of  nitrogen,  found  that  the  nitrogen 
output  per  diem  was  only  3  to  4  grm.  It  would  seem  therefore 
that  a  healthy  adult  man,  having  a  sufficient  intake  of  non-nitro- 
genous food,  need  not  metabolise  more  protein  than  suffices  to  yield 


THE  NORMAL  DIET  OF  MAN  733 

3  to  4  gnu.  of  nitrogen  per  clay,  i.e.  between  25  to  35  grm.  of  protein. 
Other  observations  have  been  made  on  vegetarians,  showing  that 
individuals  can  maintain  perfect  health  on  a  diet  containing  only 
about  34  grm.  of  protein  a  day,  and  with  a  total  calorie  value  of  1400 
to  2000.  A  series  of  experiments  have  lately  been  conducted  ?jy 
Chittenden  with  a  view  to  determining  how  far  such  a  diet  is  suitable 
to  the  average  individual,  and  especially  whether  it  can  be  continued 
for  long  periods  of  time  without  interfering  with  the  well-being  of 
the  subject  of  the  experiment.  The  general  results  of  these  experi- 
ments show  that  the  physiological  needs  of  the  body  can  be  met 
by  greatly  reduced  protein  intake  with  the  estabhshment  of  continued 
nitrogenous  equilibrium  on  a  far  smaller  amount  of  protein  food  than 
is  contained  in  the  ordinary  dietary  tables,  and  that  on  this  diet  the 
individual  in  some  cases,  far  from  suffering  in  health,  has  his  physical 
and  mental  efficiency  increased.  The  experiments  were  made  on 
various  classes  of  men  :  instructors  and  students  in  the  university, 
soldiers,  and  athletes.  In  the  case  of  Chittenden  himself  the  average 
daily  diet  contained  about  6  grm.  of  nitrogen  and  had  a  heat -value 
of  about  1600  calories.  In  the  case  of  another  individual  the  intake 
of  nitrogen  per  day  was  9"5  grm.  and  the  heat-value  of  the  food 
2500  calories.  It  is  thus  possible  to  reduce  the  total  energy  of  the 
food  from  about  3300  calories  to  about  2500  calories.  Of  the  protein 
taken  in  by  a  normal  individual  therefore  a  certain  amount  which  is 
not  needed  by  the  organism  is  at  once  broken  up  and  serves  simply 
to  increase  the  total  metabolism  of  the  body  without  serving  any 
useful  physiological  purpose  other  than  heat  production.*  Many 
ailments,  especially  of  middle  age,  have  been  ascribed  to  an  excess 
of  protein  in  the  food.  It  has  been  thought  that  the  kidneys  and 
other  organs  may  suffer  from  the  strain  of  eliminating  excess  of 
nitrogenous  waste  products.  But  the  energy  metabolism  of  proteins 
results  almost  entirely  in  the  formation  of  urea — an  innocuous  sub- 
stance which  can  have  little  harmful  effect  on  the  kidneys,  even  if 
we  assume  (an  assumption  hardly  justifiable)  that  these  organs 
(unUke  other  organs  of  the  body)  suffer  as  a  result  of  their  normal 
functional  activity.  There  is  no  doubt  that  many  disorders  of 
middle  life  may  be  put  down  to  over-feeding  and  lack  of  muscular 
exercise,  but  there  is  just  as  much  reason  to  ascribe  these  evils  to 
the  carbohydrates  as  to  the  proteins  of  the  diet.  It  is  indeed  possible 
that  an  almost  exclusive  protein  diet  might  be  more  suitable  than 
carbohydrates  for  a  sedentary  life,  where  the  normal  stimulus  to 
oxidation  of  the  food-stuffs,  viz.  muscular  exercise,  is  absent,   and 

♦But  heat  production  is  a  very  important  function  of  the  food,  and  on  the 
Chittenden  diet  tends  to  be  deficient ;  so  that  individuals  on  thi.s  r6gime  '  feel 
the  cold  '  more  than  tliey  did  wlien  on  an  ordinary  diet. 


734  PHYSIOLOGY 

that  the  '  stimulant  '  effect  of  proteins  on  metabohsm  might  have 
a  real  value  to  the  organism. 

The  limitation  of  protein  diet  to  a  mininuim  is  only  justifiable 
in  adult  healthy  men.  Where  from  any  cause  there  has  been  a 
loss  or  destruction  of  nitrogenous  tissue,  as  after  infective  diseases, 
the  body  possesses  the  power  of  storing  up  nitrogen  in  the  form  of 
flesh  or  muscular  tissue,  and  it  is  important  under  such  circumstances 
to  give  in  the  food  an  excess  of  protein  which  can  be  used  for  this 
purpose.  Moreover,  when  a  rapid  growth  of  muscle  is  going  on, 
as  during  training,  an  excess  of  protein  in  the  food  is  also  desirable, 
though  nothing  is  gained  in  pushing  this  administration  of  protein 
to  an  inordinate  extent. 

The  fact  that  in  many  cases  greater  economy  and  efficiency  of 
nutrition  are  attained  by  diminishing  the  protein  of  the  diet  affords 
no  argument  for  accepting  or  rejecting  any  given  class  of  foods.  Thus 
the  normal  requirements  of  the  individual  can  be  obtained  by  the 
administration  of  a  diet  containing  meat,  eggs,  vegetables,  and  cereals, 
or  by  a  diet  derived  entirely  from  the  vegetable  kingdom.  A  purely 
vegetable  diet  is  rendered  possible  in  civilised  countries  b)^  the  ease 
with  which  the  products  from  warmer  climates  can  be  obtained. 
A  diet  composed  only  of  the  products  of  temperate  climates  would 
tend  to  be  deficient  in  fats  and  oils.  In  such  climates  it  is  therefore 
necessary  to  import  the  oily  fruits  grown  in  warmer  lands,  or  to 
supplement  the  diet  with  such  animal  food  as  milk  or  butter  or  eggs. 
In  drawing  up  a  purely  vegetarian  diet  it  is  important  to  remember 
that  its  constituents,  especially  its  protein,  are  digested  with  greater 
difficulty  than  the  corresponding  ingredients  in  animal  food.  A 
larger  quantity  therefore  has  to  be  given  in  a  vegetable  diet  in  order 
to  allow  for  the  greater  loss  by  the  fgeces.  Any  general  reform  of 
diet  which  may  be  indicated  by  recent  physiological  experiments 
would  seem  to  lie  rather  in  the  direction  of  limitation  of  the  quantity 
of  different  articles  of  food,  perhaps  especially  of  those  rich  in  protein, 
than  in  a  limitation  to  foods  obtained  from  the  animal  or  vegetable 
kingdom.  In  certain  individuals  the  increased  bulk  of  indigestible 
residue  which  is  afforded  on  a  vegetarian  diet  presents  a  distinct 
advantage,  since  it  serves  to  promote  peristalsis  and  the  normal 
evacuation  of  the  large  bowel.  There  is  no  scientific  evidence  that 
for  the  ordinary  person  any  advantage  is  to  be  gained  by  adherence 
to  a  strictly  vegetarian  diet. 

THE  DIET  OF  THE  GROWING   ANIMAL 
Since  the  young  animal  is  smaller  than  the  adult,  it  presents  a 
greater  surface  in  proportion  to  its  bulk,  and  therefore  will  need 
more  energy  per  kilo  body  weight  than  is  the  case  with  the   adult. 


THE  NORMAL  DIET  OF  MAN 


735 


The  processes  of  growth  are  attended  moreover  with  an  active  meta- 
bolism, so  that  tlie  metabolism  is  more  energetic  in  the  young  animal 
than  in  the  adult,  even  if  we  take  into  account  the  relative  surface  in 
the  two  cases.  In  the  following  Table  is  given  a  number  of  observa- 
tions showing  the  output  of  carbon  dioxide  per  square  metre  body 
surface  at  different  ages  in  boys  and  men  : 

Effect  of  Age  on  Metabolism  (Max) 


Age 

Body  wi'ight 
kilos 

CO,  pvT  kilo  body 
weight  per  hour 

CO;  per  square  ruelre 
per  hour 

lO.V 

30 

Ml 

28-2 

14  . 

45 

1-00 

27-6 

17  . 

56 

0-81 

24-2 

23  . 

65 

0-58 

18-6 

45  . 

77 

0-48 

16-3 

58  . 

85 

0-41 

14-2 

Between  the  ages  of  fourteen  and  nineteen  years  in  boys  the 
carbon  dioxide  output  is  absolutely  greater  than  at  any  other  age. 
It  is  during  these  years  that  the  growth  of  the  boy  is  most  marked. 
A  boy  between  nine  and  thirteen  years  old  requires  just  as  much 
food  as  a  full-gro\ATi  man,  and  between  the  ages  of  fourteen  and 
nineteen  he  will  require  more.  This  great  increase  between  the 
fourteenth  and  nineteenth  years  is  not  noticed  in  females.  There  is 
a  gradual  absolute  increase  in  girls  up  to  the  eleventh  year.  At  this 
age  and  henceforward  the  total  carbon  dioxide  output  and  therefore 
the  total  food  requirements  remain  constant,  being  about  equal  to 
that  of  a  woman  of  thirty.  The  total  energy  requirements  of  the 
growing  animal  are  not,  however,  the  only  factor  which  we  have  to 
consider.  The  protein  of  the  food  has  not  only  to  replace  the 
wear  and  tear  of  tissue,  but  also  to  provide  material  for  the  growth 
of  new  tissues.  The  protein  needs  therefore  of  the  growing  animal 
are  relatively  greater  than  those  of  the  adult,  and  absolutely 
greater  during  the  period  of  most  rapid  growth,  namely,  in  boys 
between  the  ages  of  fourteen  and  nineteen.  It  is  a  popular  belief 
that  in  a  working-class  family  the  worker  or  wage-earner  needs 
a  greater  protein  supply  than  the  rest  of  the  family.  This  is  a  mis- 
take. The  adult  worker  can  obtain  his  energy  equally  well  from 
carbohydrates  and  fats,  whereas  an  excess  of  protein  is  absolutely 
necessary  in  the  case  of  the  children  to  provide  the  material  for 
their  proper  development  and  growth.  The  relation  between  rate 
of  growth  and  protein  content  of  food  is  well  illustrated  by  a  com- 
parison of  the  composition  of  the  milk  in  different  animals.  In  the 
following  Table  (Proscher)  it  will  be  seen  that  the  more  rapidly  an 


736 


PHYSIOLOGY 


animal  grows  the  greater  is  the  protein  content  of  the  milk  witli 
which  it  is  supplied  : 


Time  in  which 

the  body  weight 

of  the  new-born 

animal  was 

doubled. 

Days 

100  parts  of  Milk  contain 

Protein 

Ash 

Lime 

Phosphoric 
acid 

Man 
Horse 
Cow 
Goat 

Pig 

Sheep 

Dog 

Cat 

180 
60 

47 
19 
18 
10 

8 

7 

1-6 
2-0 
3-5 
4-3 
5-9 
6-5 
7-1 
9-5 

0-2 
0-4 

0-7 
0-8 

0-9 
1-3 

0-328 
1-240 
1-600 
2-100 

2-720 
4-530 

0-473 
1-310 
1-970 
3-220 

4-120 
4-930 

We  should  expect  then  that  the  milk  which  is  the  sole  food  of 
the  growing  infant  should  contain  a  relatively  greater  proportion 
of  protein  than  is  necessary  in  the  case  of  the  adult.  In  an  experiment 
by  E.  Feer,  quoted  by  Bunge,  a  child  weighing  8226  grm.  at  the 
thirtieth  week  took  951  grm.  of  milk.     Human  milk  contains  : 


Protein 

. 

r6  per  cent 

Fat   . 

... 

3-4       „ 

Sugar 

. 

61       „ 

Ash  . 

. 

.         0-2       „ 

The  child  was  therefore 

receiving  daily  : 

Protein 

. 

15-2  grm. 

Fat    . 

• 

.      32-3     „ 

Sugar 

•          •          • 

.      58-0      „ 

Ash   . 

. 

.        1-9      „ 

According  to  the  same  proportions  a  man  of  70  kilos  would  take  in 
Protein       .....       129  grm. 


Fat  . 
Sugar 
Ash    . 


275 

494 

16 


It  is  interesting  to  note  that  the  protein  of  this  diet  differs  but 
little  from  that  in  the  diets  ordinarily  accepted  as  standard. 


CHAPTER  X 
THE  PHYSIOLOGY  OF  DIGESTION 

CHANGES   UNDERGONE  BY  THE   FOOD-STUFFS  IN  THE 
ALIMENTARY  CANAL 

The  use  of  the  process  of  digestion  is  to  alter  the  food-stuffs  so 
as  to  fit  them  for  absorption  into  the  blood,  by  means  of  which  they 
may  be  carried  to  all  parts  of  the  body.  In  most  cases  the  food-stuffs 
cannot  be  utilised  in  their  original  form  by  the  living  cells.  When 
we  nourish  ourselves  at  the  expense  of  an  animal  or  plant,  we  are 
taking  in  not  only  the  current  coin  of  the  organism  which  is  being 
used  for  the  supply  of  energy  to  its  vital  processes,  but  also,  and  to 
a  much  larger  extent,  the  framework  forming  the  machinery  of  the 
organism  as  well  as  its  stores  of  carbohydrate  or  fat.  The  food-stuffs 
as  we  ingest  them  are  in  the  most  inactive  form  possible.  Practically 
all  are  colloidal,  neutral,  and  tasteless,  and  present  no  tendency  to 
unite  with  oxygen  or,  indeed,  to  undergo  any  change  whatsoever,  apart 
from  the  interference  of  living  organisms  such  as  bacteria.  In  a 
starving  animal  the  stores  of  carbohydrate  and  fat  and  the  protein 
structure  of  the  inactive  hving  cells  have  to  be  converted  into  a 
soluble  form — transformed,  so  to  speak,  into  currency — before  they 
can  be  utilised  by  other  living  cells,  such  as  those  of  the  heart,  for 
the  discharge  of  their  normal  functions  and  the  maintenance  of 
the  life  of  the  animal.  In  the  same  way,  when  we  take  these  colloidal 
or  insoluble  substances  into  our  alimentary  canal,  they  have  to  be 
rendered  soluble  or  diffusible,  in  order  to  allow  of  their  easy  transfer- 
ence across  the  wall  of  the  gut  into  the  blood  and  their  transport  to  the 
tissue-cells.  The  cells  of  the  body  cannot  deal  with  all  kinds  of  carbo- 
hydrate. Most  animal  cells  will  starve  when  presented  with  starch, 
dextrin,  or  any  of  the  disaccharides,  such  as  maltose,  lactose,  or  cane 
sugar.  It  is  necessary  therefore  that  all  the  carbohydrates  shall  be 
reduced  in  the  alimentary  canal  or  in  its  walls  to  the  form  of  monosac- 
charides. As  regards  proteins,  the  processes  of  digestion  have  a 
different  significance  according  as  we  are  dealing  with  their  value  as 
givers  of  energy  or  their  value  as  builders  up  of  the  living  protoplasm. 
If  the  proteins  of  the  food  are  to  be  oxidised  and  utilised  as  a  source  of 
energy,  they  must  be  rendered  soluble  so  as  to  enable  them  to  be  ab- 
sorbed and  carried  to  those  parts  of  the  body  where  they  may  undergo 

737  47 


738  PHYSIOLOGY 

deamination  and  complete  oxidation.  If  they  are  to  be  built  up  as 
integral  parts  of  living  cells,  to  take  the  place  of  molecules  which  have 
been  destroyed  in  the  wear  and  tear  of  functional  activity,  the  change 
must  be  almost  equally  profound.  The  proteins  of  the  cells  from 
different  parts  of  the  body  have  different  molecular  constitutions. 
Not  only  do  they  differ  among  themselves,  but  they  differ  very 
largely  from  many  of  the  proteins  which  may  be  taken  in  with  the 
food.  A  child  is  able  to  obtain  material  for  the  growth  of  his  brain- 
cells,  his  muscle-cells,  or  his  liver-cells,  from  a  diet  containing  protein 
in  the  form  of  caseinogen,  or  of  vegetable  gluten,  or  of  meat  fibrin. 
A  reference  to  the  Tables  on  p.  100  will  show  the  striking  difference 
in  composition  between  the  various  proteins  of  the  food  and  the 
proteins  which  have  to  be  formed  from  them  in  the  living  tissues. 
It  is  evident  that  to  form  serum  albumin,  for  instance,  out  of 
wheat  gliadin,  an  entire  reconstruction  is  necessary.  This  can  only 
be  accomplished  by  taking  the  protein  molecule  to  bits,  and  by 
selecting  certain  of  its  constituent  parts  and  building  these  up  in 
the  proper  proportions  to  form  a  new  protein  molecule.  For  the 
purposes  of  nutrition  therefore  the  changes  in  the  protein  molecule 
must  be  greater  the  more  variation  there  is  in  the  composition  of  the 
protein  of  the  food  from  the  composition  of  the  proteins  of  the 
tissues. 

In  primitive  alimentary  canals  every  cell  lining  the  canal  may 
be  endowed  with  amoeboid  properties  and  capable  of  devouring 
the  food  particles,  the  subsequent  changes  in  the  latter  to  fit  them 
for  their  journey  through  the  rest  of  the  body  being  performed  in 
the  body  of  the  cell  itself.  In  all  the  higher  animals,  however, 
including  ourselves,  the  greater  part  of  the  preparation  of  the  food 
is  accomplished  extracellularly  in  the  lumen  of  the  alimentary  canal, 
and  the  changes  are  effected  by  means  of  special  digestive  juices, 
which  are  formed  by  the  activity  of  masses  of  cells  produced  as 
outgrowths  from  the  wall  of  the  canal.  The  digestive  juices  attack 
the  food-stuffs  by  means  of  ferments,  and  in  every  case  the  action 
of  these  ferments  is  hydrolytic,  the  food-stuffs  taking  up  one  or 
more  molecules  of  water  and  undergoing  dissociation  into  simpler 
molecules.  Since  each  class  of  food-stuff  requires  a  different  ferment, 
a  great  variety  of  ferments  is  concerned  in  the  processes  of  digestion. 

As  the  end-result  of  digestion  the  many  kinds  of  food  taken  by 
man  are  reduced  to  a  fairly  small  number  of  simpler  bodies.  These 
end-products  are  : 

(1)  Carbohydrates. 

The  monosaccharides  :  glucose,  fructose  or  levulose,  and  galac- 
tose. 

(2)  Fats.    Fatty  acids,  or  (in  alkaline  medium)  soaps,  and  glycerin. 


THE  PHYSIOLOGY  OF  DIGESTION 


739 


(3)  Proteins.     Here  we  have  a  great  variety  of  mono-  and  diamino- 
acids,  which  may  be  enumerated  as  follows  : 

MONO-AMINO-AOIDS 

Glycine  (aminoacetic  acid)    . 

Alanine  (aminopropionio  acid) 

Serine  or  oxyalanine  (oxyamino propionic  acid) 

Aminovalerianic  acid    . 

Leucine  (aminoisobutylacetic  acid) 

Isoleucino  (aminocaproic  acid) 

A-spartio  acid        .... 

Glutamic  acid      .... 

Phenylalanine      .... 

Tjrrosine  (oxyphenylalanine) 

Proline  (pyrrolidine  carboxylic  acid) 

Oxyproline  (oxypyrrolidine  carboxylic  acid) 


Monobasic  acids 
of  fatty  series 


Dibasic  acids 

Benzene  (aromatic) 
derivatives 

Heterocyclic 

compounds 


Tryptophane  (indolaminopropionic  acid) 

DlAMINO-ACIDS   AND   THEIR   COMPOITNDS 

Lysine  (diaminocaproic  acid)  ....  1  rj^he 

I        '  hexone  bases 


Arginine  (guanidinaminovalerianic  acid) 

Histidine  (iminazolalanine) 

'  Diaminotrioxydodecoic  acid '       .         .         . 

Cystine  (derived  from  aminothiopropionic  acid) 


derived  from  a  12-carbon  acid 
j  Sulphur-containing 
t  body 


Those  constituents  of  the  food  which  undergo  no  oxidation  in 
the  body,  such  as  the  water  and  salts,  are  practically  unchanged 
in  the  alimentary  canal,  and  are  absorbed  in  their  original  form  into 
the  blood. 


SECTION  I 
DIGESTION  IN  THE  MOUTH 


It  is  a  common  experience  that  when  food  is  taken  into  the  mouth 
there  is  a  flow  of  a  liquid,  *  saUva,'  into  this  cavity.  Saliva 
is  the  product  of  secretion  of  three  pairs  of  large  salivary  glands 
situated  in  the  neighbourhood  of  the  mouth  and  pouring  their  secre- 
tions into  this  cavity  by  means  of  ducts 
It  is  possible  to  collect  the  fluid  secreted 
by  each  of  these  glands  separately,  and  it 
is  found  that  the  saliva  varies  in  pro- 
perties according  to  the  gland  from  which 
it  is  derived.  In  addition  to  these  large 
glands  the  whole  mucous  membrane  of 
the  mouth  is  beset  with  small  glands. 

The  saliva  is  in  most  cases  a  mixture 

of  the  secretions  of  all  three  pairs  of 

salivary  glands  as  well  as  of  the  small 

^  ^.  ,.    ,      ,      glands  of  the  mucous  membrane.    "When 

Fig.  319.    Dissection  to  display  the    "  -,     •       r  i        i 

salivary  glands.  Collected  it  forms  a  colourless  cloudy 

a,  sub-lingual  gland  ;  b,  sub-   liquid,  sUmy  in  character.     The  cloudi- 

maxillary     gland ;      c,     parotid  •      i        a.     j.i.  x  i. 

gland ;   d,  common  opening  of   ^ess  IS  due  to  the  presence  of  a  number 
ducts  of  sub-maxillary  and  sub-   of  formed  elements   Consisting  of  des- 

lingual    glands;    i,    opening    of  .     ^        -j^i     t    i       n        t   •    j 

duct  of  parotid  gland  quamated  epithebal  cells,  dismtegrating 

leucocytes,  and  gland-cells,  as  well  as 
coagulated  clumps  of  mucin.  Its  reaction  is  in  healthy  individuals 
slightly  alkaline.  Its  specific  gravity  varies  between  1002  to  1008. 
Its  chief  constituents  are  coagulable  proteins,  mucin,  and  in  some 
cases  a  diastatic  ferment,  ptyalin,  and  traces  of  potassium  sulpho- 
cyanate.     Its  average  composition  is  as  follows  : 


100  parts  mixed  saliva i;ontain  : 

lotal  solids 0-5    to  1-0 

Inorganic  solids    ........  0-4    to  0-6 

Organic  solids  (mucin,  serum  albumin,  serum  globulin)     .  0-1    to  0-4 

Potassium  sulphocyanate       ......  0-00  to  0-016 

Freezing-point  (A)  =   -  0  07  to  -  0-34 

Potassium  sulphocyanate  is  an  almost  constant  constituent  of  human  saliva, 

though  it  is  often  absent  in  that  of  other  animals,  such  as  the  dog.  It  is  generally 

740 


DIGESTION  IN  THE  MOUTH  741 

present  to  the  extent  of  '01  per  cent,  so  that  on  the  addition  of  a  drop  of  ferric 
chloride  to  saliva  a  definite  red  clour  is  obtained.  So  far  as  we  know  it  is  formed 
in  the  body  whenever  cyanides  or  organic  nitriles  in  small  quantities  make  their 
appearance  in  the  circulating  fluid,  either  as  the  result  of  adminLstration  or 
perhaps  as  by-product.s  in  the  normal  processes  of  metabolism.  The  conversion  of 
the  poisonous  cyanides  into  th";  almost  innocuous  sulphocyanates  seems  to  be  a 
means  by  which  the  organism  protects  itself  against  the  poisonous  effects  of  the 
former.  The  channels  of  excretion  of  the  sulphocyanat©  are  by  the  salivary 
glands,  the  kidneys,  and  possibly  by  the  gastric  juice. 

THE  USES  OF  SALIVA 
The  main  function  of  saliva  is  to  moisten  the  food  and  so  facilitate 
its  mastication  and  deglutition.  The  presence  of  the  mucin  is 
of  special  value  for  the  latter  process  since  it  renders  the  mass  of 
food  slippery.  In  animals,  such  as  dogs,  where  the  saliva  is  devoid  of 
any  digestive  ferment,  this  must  represent  its  sole  function.  In  man 
and  some  of  the  herbivora  the  saliva  exerts  a  well-marked  digestive 
effect  on  one  of  the  food-stuffs,  namely,  starch.  If  a  warm  solution 
of  starch  be  taken  into  the  mouth,  kept  there  for  one  minute,  and 
then  expelled  into  a  test-tube,  the  starch  will  be  found  to  have  entirely 
disappeared,  its  place  being  taken  by  a  reducing  sugar.  The  stages 
of  the  action  of  saliva  on  boiled  starch  can  be  followed  more  easily 
if  its  action  is  retarded  by  keeping  the  mixture  cool,  or  at  a  tempera- 
ture not  above  25°  C.  The  first  change  is  a  conversion  of  the 
opalescent  gelatinising  starch  solution  into  a  clear  solution  which 
no  longer  sets  on  cooling,  but  still  gives  a  blue  colour  with  iodine. 
The  fluid  contains  what  is  known  as  soluble  starch.  The  soluble 
starch  then  undergoes  hydrolytic  dissociation  into  a  dextrin,  which 
gives  a  red  colour  with  the  iodine  and  is  therefore  known  as  erythro- 
dextrin,  together  with  maltose.  The  erythrodextrin  is  then  hydro- 
lysed  into  an  achroodextrin  (giving  no  colour  with  iodine)  and  maltose, 
and  the  achroodextrin  is  still  further  broken  up  into  dextrin  and 
maltose.  The  conversion  of  starch  into  maltose  is  never  complete, 
though  if  the  maltose  be  removed  by  dialysis  as  it  is  formed,  it  was 
found  by  Lee  to  be  possible  to  convert  as  much  as  95  per  cent,  of  the 
starch  into  reducing  sugar.  The  stages  in  the  conversion  are  repre- 
sented in  the  following  Table  : 

Starch 

I 
soluble  starch 


(erythro-)  dextrins  maltose 


(achroo-)  dextrins  maltose 


742  PHYSIOLOGY 

The  process  by  which  the  huge  starch  molecule  is  converted  into 
dextrins  and  maltose  is  a  very  complicated  one,  and  a  number  of 
intermediate  compounds  of  dextrins  and  maltose  can  exist  between 
those  whose  presence  is  revealed  by  their  varying  reaction  to  iodine. 

Ptyalin  is  most  active  in  a  neutral  medium,  so  that  the  addition 
of  minute  traces  of  acid  to  the  saUva  increases  its  diastatic  power. 
In  the  presence  of  free  mineral  acid  ptyalin  is  rapidly  destroyed, 
•003  per  cent,  hydrochloric  being  sufficient  for  this  purpose.  It  acts 
most  rapidly  at  the  body  temperature.  At  0°  C.  its  action  is  still 
just  perceptible.     If  heated  to  60°  C.  it  is  destroyed. 

We  have  seen  that  boiled  starch  solution  is  changed  by  saliva 
when  kept  only  a  few  seconds  in  the  cavity  of  the  mouth.  When 
the  starch  is  in  the  solid  condition,  as  in  biscuits  and  most  farinaceous 
foods,  its  stay  in  the  mouth  during  the  normal  process  of  mastication 
is  not  long  enough  to  allow  of  any  considerable  hydrolysis  occurring. 
When  a  meal  is  taken  the  food  which  is  swallowed  forms  a  mass  lying 
in  the  fundus  of  the  stomach.  This  mass  is  penetrated  only  with 
difficulty  by  the  acid  gastric  juice  secreted  by  the  mucous  membrane 
of  the  stomach  within  five  minutes  of  the  taking  of  food.  Even 
half  an  hour  after  a  meal  the  interior  of  the  mass  of  food  in  the 
stomach  may  be  still  found  to  be  neutral  or  slightly  alkaline.  The 
food  therefore,  thoroughly  moistened  by  and  mixed  with  saliva, 
remains  in  the  stomach  for  thirty  to  forty  minutes  before  the  salivary 
ferment  is  destroyed  by  the  penetration  of  the  acid  gastric  juice. 
During  this  time  the  ptyalin  continues  to  exert  its  effect,  so  that 
we  may  say  that  the  chief  part  of  the  salivary  digestion  occurs 
actually  in  the  stomach,  and  results  in  an  almost  complete  alteration 
of  the  starch  into  dextrins  and  maltose.  Unboiled  starch  is 
attacked  with  extreme  slowness  by  the  diastatic  ferments  either 
of  the  saliva  or  the  pancreatic  juice,  so  that,  if  taken  by  man,  large 
quantities  are  unutilised  and  reappear  in  the  faeces.  Thirty  to  forty 
minutes  after  a  meal  the  food  becomes  thoroughly  soaked  with  the 
acid  gastric  juice,  and  salivary  digestion  gives  place  to  gastric  digestion. 

THE  SECRETION  OF  SALIVA 
The  mucous  membrane  of  the  mouth,  especially  on  the  under 
surface  of  the  tongue,  presents  a  number  of  small  glands  which 
contribute  by  their  secretions  to  the  moistening  of  the  mouth. 
The  greater  part  of  the  saUva  is,  however,  formed  in  man  by  three 
pairs  of  glands,  viz.  the  sub-lingual  and  the  sub-maxillary  glands, 
situated  in  the  floor  of  the  mouth  below  the  jaw,  and  the  parotid 
gland,  lying  in  the  cheek  over  the  ramus  of  the  superior  maxilla. 
The  arrangement  of  these  glands,  especially  of  those  in  the  floor  of 
the  mouth,  varies  somewhat  in  different  animals.     In  the  dog  and  cat 


DIGESTION  IN  THE  MOUTH 


743 


the  sub-lingual  gland  is  wanting,  its  place  being  taken  by  a  gland 
situated  somewhat  further  back  and  known  as  the  retro-lingual 
gland.  In  the  pig  both  retro-hngual  and  sub-lingual  glands  are 
present  in  addition  to  the  sub-maxillary,  and  one  may  sometimes 
find  traces  of  the  retro-hngual  gland  in  man.  Many  animals,  e.g. 
the  dog,  also  possess  a  gland  situated  in  the  orbit,  which  pours  its 
secretion  into  the  mouth — the  orbital  gland.  These  glands  can  be 
divided,  according  to  their  structure  and  the  nature  of  the  secretion 
which  they  form,  into  several  classes.  Among  the  saUvary  glands 
of  the  mucous  membrane  we  may  distinguish  two  types,  the  mucous 
gland  and  the  serous  gland.  In  specimens  hardened  and  stained 
in  the  ordinary  methods  the  mucous  gland  is  distinguished  by  the 
fact  that  its  short  duct  opens  into  wide  alveoli,  the  lining  cells  of 


^^211  W^m^ 


Fig.  320.    a,  serous  gland  ;  b,  pure  mucous  gland  from  mouth.    (Kollikbb.) 
a,  ducts  ;  /,  fat-cells. 

which  are  distended  with  mucin  and  therefore  present  a  clear 
unstained  space  in  the  section.  In  the  other  type,  the  serous  gland, 
the  duct  lined  with  columnar  cells  branches  into  a  series  of  acini 
which  present  a  well-marked  lumen  and  are  lined  with  small  granular 
cells  with  a  very  distinct  and  well-staining  nucleus.  The  same  general 
distinction  can  be  made  out  in  the  large  salivary  glands.  The  parotid 
gland  in  man  and  in  all  the  higher  mammaUa  is  a  typical  serous 
gland,  though  here  and  there  a  mucous  cell  may  be  occasionally  seen. 
The  orbital  gland  of  the  dog  represents  practically  one  of  the  mucous 
glands  of  the  general  mouth  cavity  on  a  large  scale.  The  sub- lingual 
and  sub-maxillary  glands  in  man  represent  a  third  type.  Most 
of  the  alveoli  are  mucous  in  character.  At  the  ends  of  the  alveoli 
are  seen  crescent-shaped  cells  between  the  mucin-distended  cells  and 
the  basement  membrane.  These  are  known  as  the  demilune  cells,  or  the 
crescent  cells  of  Gianuzzi.  In  some  cases  these  mucous  alveoU  with 
demilunes  maybe  found  alongside  of  typical  serous  alveoh. 

Thus  in  man  the  sub-maxiUary  gland  is  usually  a  mixed  gland,  the  sorouj 
alveoU  predominating.  The  sub-lingual  gland  is  also  mixed,  but  with  a  pre- 
dominance of  the  mucous  alveoli.  In  the  monkey  the  eub-maxillary  gland 
is  almost  entirely  serous.     In  the  dog  the  sub-maxillary  gland  is  a  pure  mucous 


744  PHYSIOLOGY 

gland  with  demilunes,  while  the  retro -lingual  and  sub -Ungual  gland  when  present 
are  of  the  mixed  type.  In  the  rabbit  the  sub-maxUlary  gland  is  serous,  while 
the  sub-lingual  gland  is  mucous.  In  the  cat  the  sub-maxillary  is  mucous,  the 
retro-lingual  is  mixed,  and  the  sub-lingual,  when  present,  is  mixed,  with  pre- 
dominance of  the  mucous  type. 

The  normal  behaviour  of  the  sahvary  glands  during  digestion 
is  best  studied  in  a  method  used  long  ago  by  De  Graaf  and  reintro- 
duced with  considerable  elaboration  of  late  years  by  Pawlow.  It 
is  possible  without  any  disturbance  of  the  animal's  nutrition  to 
transplant  the  papiUa  on  which  the  duct  opens  to  the  outside  so 
that  the  saliva  from  any  particular  gland  shall  flow  externally  instead 
of  into  the  cavity  of  the  mouth.  By  attaching  a  small  funnel  to  the 
fistulous  opening,  it  is  possible  to  collect  the  pure  saliva  unmixed 
with  the  secretion  of  any  other  of  the  glands. 

By  this  method  it  has  been  found  that  as  soon  as  food  is  intro- 
duced into  the  mouth  there  is  a  secretion  of  saliva,  the  relative  extent 
to  which  different  glands  are  involved  varying  according  to  the 
nature  of  the  stimulation.  Thus  with  meat  there  is  only  a  small 
amount  of  secretion,  which  is  derived  chiefly  from  the  sub-maxillary 
and  sub-lingual  glands,  and  is  rich  in  organic  constituents.  When 
dry  material,  such  as  dry  powdered  meat,  is  introduced  the  flow  of 
juice  is  more  copious  and  more  watery.  The  same  effect  may  be 
produced  in  the  dog  by  psychic  excitation.  Thus  saHvation  may 
be  induced  by  showing  food  to  the  dog,  or  even  by  the  suggestion 
that  dry  powder  is  to  be  introduced  into  the  mouth.  A  comparison 
of  the  juices  obtained  from  different  glands  shows  that  the  serous 
and  mucous  glands  differ,  as  might  be  expected,  in  the  nature  of 
their  secretion.  A  serous  gland,  such  as  the  parotid,  gives  a  thin 
watery  secretion  almost  free  from  mucin,  but  containing  small  traces 
of  coagulable  protein.  The  mucous  gland  dehvers  a  secretion  which 
is  viscid  from  the  presence  of  mucin,  and  contains  also  a  small  trace 
of  coagulable  protein.  Both  in  parotid  and  mucous  sahva  the  per- 
centage of  salts  is  very  low,  so  that  the  freezing-point  of  these  fluids 
is  considerably  higher  than  that  of  the  blood  plasma.  In  the  dog 
the  saliva  is  free  from  any  ferments.  In  man  ptyalin — ^the  starch- 
spUtting  ferment — is  found  in  the  saliva  from  both  kinds  of  gland, 
though  it  predominates  in  that  obtained  from  the  parotid  gland. 
The  total  amount  of  saliva  which  may  be  obtained  varies,  of  course, 
in  different  animals.  Each  gland  may,  however,  in  the  course  of 
the  day  give  an  amount  of  juice  far  exceeding,  e.g.  ten  or  twelve  times, 
its  own  weight.  In  man  it  is  reckoned  that  over  one  litre  of  sahva 
may  be  formed  every  twenty-four  hours,  and  in  the  herbivora,  such  as 
the  horse,  the  total  diurnal  production  must  amount  to  many  Utres  ; 
500  grammes  of  hay  alone  may  evoke  the  secretion  of  a  litre  of  sahva. 


DIGESTION  IN  THE  MOUTH  745 

The  intimate  dependence  of  the  secretion  of  sahva  on  the  events 
occurring  in  the  mouth  shows  that  the  activity  of  the  salivary  glands 
must  be  excited  by  reflex  means.  The  afferent  nerves  in  this  reflex 
are  those  that  supply  the  mucous  membrane  of  the  mouth,  i.e.  the 


Fig,  321.     Diagram  of  nerve-supplj'  to  sub-maxillary  gland. 
Sm.G,  sub-maxillary  gland ;  N.L,  lingual  nerve  ;  Ch.T,  chorda  tympani ; 
Sm.Gl,  sub-maxillary  ganglion ;  Sm.D,  ^Vllarton's  duct ;  V.J,  jugular  vein ; 
O.A,  carotid  artery  ;  G.C.S,  superior  cervical  ganglion ;  N.S,  sympathetic  fibres 
ramifying  on  facial  artery.     (After  Foster.) 

fifth  nerve  and  the  glossopharyngeal.  The  efferent  channels  of  the 
reflex  were  discovered  by  Ludwig.  Each  one  of  the  large  saUvary 
glands  receives  nerve  fibres  from  two  sources,  viz.  from  the  cerebro- 
spinal   and    from   the   sympathetic    system.     It   is   probable   that 


Mylohyoid 


ingual .  N 


HyogflofSUS 


Geniohyoid 


Fig 


322.     Diagram  of  the  arrangement  of  the  nerve-supply  to  the  sub- 
maxillary gland,  as  exposed  in  an  actual  experiment. 
Duct.Wh,   Wharton's   duct  (of  sub-maxillary);    Duct.R.L.  retro-lingual 
duct;  Ch.Ty,  chorda  tympani  nerves.     (Alcock  and  Eiiisoy.) 

the  cerebrospinal  supply  is  derived  always  from  one  part  of 
the  cerebral  axis,  namely,  from  the  filaments  which  make  up  the 
nervus  intermedins.  From  this  point  they  diverge  in  their  course 
to  the  glands.  The  fibres  to  the  sub-maxillary,  the  sub-lingual, 
and  the  retro-lingual  glands  pass  into  the  facial  nerve,  and   then 


746  PHYSIOLOGY 

from  this  nerve  along  the  chorda  tympani  to  the  lingual  division 
of  the  fifth  nerve.  The  lingual  nerve  passes  below  the  duct,  and 
just  before  it  crosses  the  two  ducts  of  the  sub-maxillary  and  retro- 
or  sub-lingual  glands  it  gives  off  a  small  branch  backwards,  namely, 
the  chorda  tympani,  which  runs  along  the  sub-maxillary  duct  to  be 
distributed  to  the  glands,  and  in  its  course  gives  ofE  fibres  also  to  the 
retro-Hngual  (Fig.  321). 

The  fibres  are  apparently  fijially  distributed  to  the  secreting 
alveoli,  where  they  end  freely  on  the  secreting  cells  just  below  the 
basement  membrane.  They  do  not,  however,  take  an  uninterrupted 
course.  By  means  of  the  nicotine  method  Langley  has  shown  that  all 
the  fibres  to  the  sub-lingual  and  the  sub-maxillary  glands  end  some- 
where near  the  glands  in  connection  with  ganghon-cells.  From  the 
ganglion-cells  fresh  relays  of  fibres  are  given  off  which  pass  to  the 
gland-cells  themselves.  The  fibres  going  to  the  sub-maxillary  gland 
are  connected  with  scattered  cells  lying  in  the  substance  of  the  gland 
itself ;  those  passing  to  the  retro-lingual  gland  are  connected  for  the 
most  part  with  ganglion- cells  which  make  up  the  so-called  '  sub- 
maxillary ganglion.' 

The  fibres  to  the  parotid  gland  pass  along  the  glossopharyngeal 
nerve  and  its  tympanic  branch  (nerve  of  Jacobson)  to  the  tympanic 
plexus.  Hence  the  fibres  are  carried  by  the  Vidian  nerve  to  the 
otic  ganghon,  and  from  this  ganghon  by  a  communicating  branch 
to  the  second  division  of  the  fifth  nerve  ;  by  the  auriculo-temporal 
branches  of  this  nerve  the  fibres  are  carried  to  the  gland. 

The  sympathetic  supply  to  all  these  glands  is  contained  in  fine 
filaments  on  the  walls  of  the  arteries  with  which  they  are  supphed. 
The  fibres  are  derived  ultimately  from  the  spinal  cord,  whence  they 
issue  by  the  upper  three  anterior  dorsal  nerve-roots.  They  pass 
into  the  stellate  ganghon,  round  the  ansa  Vieussenii  to  the  inferior, 
and  so  to  the  superior  cervical  ganghon  of  the  sympathetic.  Here 
the  fibres  end  around  the  cells  of  the  ganglion,  and  a  fresh  relay 
of  fibres,  chiefly  non-medullated,  arise  from  the  cells  and  travel 
on  the  walls  of  the  branches  of  the  external  carotid  artery  to  their 
destination. 

The  effect  of  stimulating  the  peripheral  ends  of  the  cerebro- 
spinal nerves  going  to  the  glands  presents  a  general  resemblance, 
whichever  be  the  gland  involved.  Within  a  period  of  half  to  two 
seconds  after  the  stimulation  has  been  applied,  a  secretion  of  sahva 
is  produced,  presenting  similar  characters  to  that  which  would  be 
obtained  from  the  gland  under  normal  conditions  if  it  were  provided 
with  a  permanent  fistula.  The  concentration  of  the  sahva  as  well 
as  its  rate  of  secretion  depends  on  the  strength  of  the  stimulus.  The 
following  Table  (Heidenhain)  shows  the  effect  on  the  amount  and 


DIGESTION  IN  THE  MOUTH 


741 


composition  of  sub-maxillary  saliva  obtained  by  weak  and  strong 
stimulation  of  the  chorda  tympani  nerve  : 


strength  of  stimulus 

Quantity  in  one 
minute 

Per  cent,  of 
organic  solids 

Per  cent,  of 
salts 

Weak      . 
Strong    . 
Weak      . 

017 

0-72 
(»-17 

0-84 
206 
1-67 

0-20 
0-46 
0-2G 

With  the  strong  stimulus  the  amount  of  sahva  was  increased 
over  fourfold,  w^hile  the  percentage  of  organic  substances  in  the 
saliva  was  raised  from  0-84  to  2-06  per  cent.  There  was  at  the  same 
time  an  increase  in  the  percentage  of  salts.  If  the  excitation  be 
continued  for  a  considerable  time,  there  is  a  gradual  rise  in  the  per- 
centage of  inorganic  salts  and  a  fall  in  the  percentage  of  organic  matter. 

The  cranial  nerves  going  to  these  glands  have  another  important 
effect,  namely,  vaso-dilatation.  It  was  shown  by  Claude  Bernard 
that  if  the  outflow  from  the  vein  of  the  sub-maxillary  gland  were 
measured,  on  exciting  the  chorda  tympani  the  flow  might  increase 
four  to  eight  times,  and  indeed  to  such  an  extent  that  the  blood 
passing  through  the  gland  did  not  stay  there  long  enough  to  lose  its 
oxygen.  Moreover  the  dilatation  of  the  arterioles  removes  the 
normal  resistance  which  serves  to  damp  and  obliterate  the  pulse 
between  the  arteries  and  the  veins.  As  the  result  of  exciting  the 
chorda  therefore  the  blood  coming  from  the  vein  may  show  distinct 
pulsation,  and  may  have  a  brilliant  scarlet  hue  just  as  if  it  were 
derived  from  an  artery.  The  same  dilatation  has  been  observed  to 
attend  excitation  of  the  cranial  supply  to  the  parotid  gland. 

The  effects  of  exciting  the  sympathetic  nerve  supply  differ  according 
to  the  gland  and  the  animal  which  is  the  subject  of  experiment. 
In  the  dog  excitation  of  the  cervical  sympathetic  causes  the  secretion 
of  a  few  drops  of  thick  viscid  saUva  from  the  sub-maxillary  gland. 
In  this  animal  no  secretion  is  obtained  at  all  from  the  parotid 
gland  on  exciting  the  sympathetic,  but  the  influence  of  the  excita- 
tion is  shown  by  the  occurrence  of  histological  changes  in  the 
gland-cells.  In  the  cat  the  sub-maxillary  saliva  obtained  on  sym- 
pathetic excitation  may  be  as  copious  as  and  even  more  watery 
than   the   saUva   obtained   from   the   sub-maxillary   on   stimulation 

of  the  chorda  tympani.     We  shall  have  later  on  to  discuss  how  far 

these  results  are  to  be  ascribed  to  a  fundamental  difference  in  the 
point  of  attack  of  impulses  carried  to  the  secreting  cells  by  the  two 
sets  of  nerve  fibres,  and  how  far  to  the  varying  effects  of  the  cranial 
and  sjnnpathetic  nerves  respectively  on  the  blood-vessels.     It  must 


748 


PHYSIOLOGY 


be  remembered  that  the  sympathetic  nerve  carries  the  vaso-con- 
strictor  fibres  to  most  or  all  of  the  vessels  of  the  head  and  neck,  and 
therefore  in  most  cases  we  should  expect,  and  we  find,  that  stimulation 
of  this  nerve  causes  vascular  constriction  in  the  gland  affected. 
Before  attempting  to  decide  this  point  we  must  study  in  somewhat 
greater  detail  the  changes  which  occur  in  the  gland  concomitantly 
with  the  secretion. 


;L_ymph  spaces 


,  'Secreting 
cells. 

♦^'-  -  Blood 
'^1       capillary. 


Basemenb 
membrane 

Fig.  323.  Diagram  to  show  relation  of 
the  secreting  cells  of  a  gland  to  the 
blood  and  lymph  supply. 


Duct. 


CHANGES  IN  THE  GLAND   ACCOMPANYING  SECRETION 
The  fact  that  a  sub-maxillary  gland  of  the  dog  under  favourable 
conditions  will  secrete  its  own  weight  of  saliva  in  five  minutes,  and  will 

continue  to  secrete  for  many  hours 
afterwards,  shows  that  there  must 
be  a  continual  renewal  of  the  fluid 
which  is  turned  out  in  the  secretion. 
The  source  of  this  fluid  must  be  the 
blood  which  is  circulating  through 
the  gland.  If  we  refer  to  the  dia- 
grammatic representation  of  the 
elements  which  make  up  a  secreting 
lobule  and  which  may  be  involved 
in  the  act  of  secretion  (Fig.  323),  we 
see  that  between  the  lumen  of  the 
duct  and  the  blood,  which  must  be 
regarded  as  the  source  of  the  fluid, 
the  following  layers  of  cells  intervene  :  (1)  the  endothehum  of  the 
blood  capillaries  ;  (2)  the  basement  membrane  ;  (3)  the  epithelial 
cells  of  the  gland  proper.  We  have,  in  the  first  place,  to  decide 
to  which  of  these  elements  can  be  ascribed  the  chief  part  in  the  act 
of  secretion. 

The  secretory  activity  of  the  sub-maxillary  gland,  whether  evoked 
reflexly  by  the  introduction  of  acids  into  the  mouth  or  directly  by  the 
injection  of  pilocarpine  or  by  stimulation  of  the  peripheral  end  of  the 
chorda  tympani  nerve,  is  always  associated  with  a  considerable  dilata- 
tion of  the  vessels  of  the  gland,  and  a  consequent  large  increase  in  the 
blood  flow  through  the  gland  which  may  amoimt  to  between  three  and 
eight  times  the  quantity  passing  during  rest.  Such  an  increase  in  the 
supply  of  blood  is  necessary  in  order  to  afford  a  source  for  the  large 
quantity  of  fluid  which  is  turned  out  in  the  saliva.  Another  effect  of 
the  dilatation  will  be  to  raise  the  pressure  in  the  capillaries  of  the 
gland.  We  cannot,  however,  regard  this  rise  of  pressure  in  the  capil- 
laries as  an  essential  factor  in  the  act  of  secretion.  If  atropine  be 
administered  excitation  of  the  chorda  causes  the  same  vaso-dilatation 
as  before,  though  no  secretion  is  produced.     Moreover  Ludwig  showed 


DIGESTION  IN  THE  MOUTH  749 

that  the  force  "with  which  the  secretion  is  turned  out  into  the  ducts 
of  the  gland  is  greater  than  that  represented  by  the  blood  pressure. 
The  blood  pressure  in  the  capillaries  must  be  considerably  lower  even 
with  full  vascular  dilatation  than  the  pressure  in  the  carotid  artery.  If 
two  manometers  be  connected,  one  with  the  carotid  artery  and  the  other 
with  the  duct,  it  will  be  found  that  on  stimulating  the  chorda  tympani 
nerve  the  secretion  will  be  excited,  and  the  mercury  will  be  driven 
up  by  the  pressure  of  the  secretion  in  the  corresponding  manometer 
until  it  attains  a  height  which  may  be  double  that  of  the  mercury 
in  the  manometer  connected  with  the  carotid  artery,  and  therefore 
must  be  still  greater  than  the  pressure  in  the  capillaries  of  the 
gland.  This  experiment,  which  is  easy  to  repeat,  showed  the 
impossibility  of  the  act  of  secretion  being  in  any  way  determined  by 
a  process  of  filtration.  We  have  now  further  evidence  that  work 
is  done  in  the  production  of  the  salivary  secretion,  e\'idence  which 
was  not  available  when  Ludwig  first  carried  out  the  experiment 
just  described.  When  a  fluid  containing  salts  in  solution  is  filtered 
through  a  porous  membrane  the  filtrate  has  the  same  content  in 
salts  as  the  original  fluid.  We  can  effect  a  separation  of  dissolved 
salts  from  a  fluid  by  filtration  under  pressure  through  some  membrane 
which  is  impermeable  to  the  salts,  e.g.  a  membrane  of  copper 
ferrocyanide — a  so-called  semipermeable  membrane.  Under  these 
circumstances  a  very  large  pressure  is  necessary  in  order  to  cause 
the  filtration  of  any  fluid  at  all,  a  pressure  which  is  equal  to  the 
osmotic  pressure  exerted  by  the  substances  in  solution.  Thus  if 
we  were  filtering  a  1  per  cent,  solution  of  XaCl  through  a  semi- 
permeable membrane,  we  should  have  to  exert  a  pressure  of  about 
seven  atmospheres  in  order  to  obtain  a  filtrate  free  from  sodium 
chloride.  To  obtain  a  filtrate  containing  half  the  amount  of  sodiimi 
chloride,  if  such  were  possible,  would  therefore  need  a  pressure  of 
about  three  and  a  half  atmospheres.  On  comparing  the  osmotic 
pressures  of  saliva  and  blood  respectively — and  for  this  purpose  we 
can  employ  the  depression  of  freezing-point  as  our  index — we  find 
that  the  molecular  concentration  of  saliva,  and  therefore  its  osmotic 
pressure,  is  always  very  much  less  than  that  of  the  blood  plasma, 
and  may  vary  between  half  and  three-quarters  of  the  latter.  Sup- 
posing the  membrane  separating  the  lumen  of  the  duct  from  the 
blood-vessels  could  be  regarded  as  endowed  with  the  properties  of 
a  semipermeable  membrane,  we  should  need,  in  order  to  effect  the 
separation,  a  pressure  ten  to  twenty  times  as  large  as  the  arterial 
blood  pressure.  We  must  conclude  then  that  work,  both  osmotic 
and  mechanical,  is  performed  in  the  separation  of  the  fluid  from 
the  blood  and  its  transference  in  the  form  of  saliva  to  the  duct.  A 
very  simple  experiment  will  suffice  to  show  that  this  work  must  be 


750 


PHYSIOLOGY 


effected,  not  by  the  endothelial  cells  of  the  blood-vessels,  but  by 
the  gland- cells  themselves.  The  secretion  passes  from  the  blood- 
vessels first  into  the  lymphatic  spaces,  whence  it  is  taken  up  by 


Fig.  324.  Tracing  of  volume  of  sub-maxillary  gland,  showing  effect  of  stimu- 
lation of  the  chorda  after  administration  of  10  mg.  atropine.  The  blood- 
pressure  (lowest  line)  was  unaltered  by  the  stimulation.     (Bunch.) 

the  secretory  cells.  If  the  first  act  in  secretion  consisted  in  an 
increased  exudation  of  fluid  from  the  blood  into  the  lymph  spaces 
the  first  effect  of  exciting  the  chorda  tympani  nerve  should  be  to 
cause  an  accumulation  of  fluid  in  the   lymph  spaces,  some   increase 


Fig.  325. 


Tracing  of  volume  of  sub-maxillary  gland  showing  decrease  on 
excitation  of  chorda.     (Bxtnch.) 


in  the  lymph  flow  from  the  gland,  and  the  swelhng  of  the  whole 
gland.  By  placing  the  gland  in  a  plethysmograph  we  can  record 
the  actual  changes  in  its  volume  which  ensue  on  excitation  of  the 
chorda   tympani.     If   all   secretion    be   prevented   by  the   previous 


DIGESTION  IN  THE  MOUTH 


751 


administration  of  atropin,  stimulation  of  this  nerve  produces,  as 
might  be  anticipated,  an  increased  volume  of  the  gland  in  consequence 
of  the  dilatation  of  its  vessels  (Fig.  324).  If,  however,  the  gland  be 
allowed  to  secrete  we  obtain,  in  spite  of  the  simultaneous  increase 
in  size  of  the  vessels,  an  actual  diminution  in  the  size  of  the  gland 
itself,  showing  that  the  first  effect  of  the  stimulation  is  on  the  cells  of 
the  alveoli  (Fig.  325).  Under  the  stimulus  these  empty  themselves  of 
the  fluid  they  contain,  replenishing  their  loss  at  the  expense  of  the 
fluid  in  the  lymph  spaces.  The 
increased  passage  of  fluid  from 
blood  to  lymph  space  is  there- 
fore a  secondary  and  not  a 
primary  effect  of  the  nerve 
stimulation,  and  the  first  effect 
on  the  gland  is  a  diminution 
of  volume  and  not  an  increase, 
as  one  would  expect  if  the 
vascular     endothehum     were 

primarily   responsible    for   the    Fig.  326.     Mucous    cells   from   a    fresh   sub- 
act  of  secretion. 


maxillary  gland  of  a  dog.     (L angle y.) 

a,  mucous  cell  examined  fresh  from  a 
resting  gland ;  a',  the  same  cell  treated 
with  weak  alcohol ;  b  and  b',  cells  from  a 
discharged  gland  before  and  after  treatment 
with  weak  alcohol. 


HISTOLOGICAL  CHANGES 

DURING  SECRETION 
The  process  of  secretion  is 
associated  with  marked  changes 
in  the  structure  of  the  cells  com- 
posing the  secretory  alveoli. 
The  changes  are  of  the  same 
general  character  whatever 
class  of  glands  we  investigate, 
though  the  ease  with  which  ]  k,  S2', 
they  are  to  be  demonstrated 
varies  with  the  reactions  of  the 
various  glands  to  the  hardening 

fluids  usually  employed.  If  a  small  fragment  of  a  mucous  gland 
be  teased  in  blood  serum  or  in  2  per  cent.  NaCl  solution,  the  cells 
are  found  to  be  packed  with  a  mass  of  coarse  highly  refractive 
granules  (Fig.  326).  If  a  corresponding  specimen  be  made  from 
a  serous  gland  (Fig.  327)  the  cells  are  also  packed  with  gi-anules, 
which,  however,  are  much  finer  in  structure.  On  making  similar 
specimens  from  glands  which  have  been  forced  to  secrete  for  six  or 
seven  hours,  the  individual  cells  are  found  to  be  much  smaller  and 
the  protoplasm  of  the  cell  is  absolutely  or  relatively  increased  in 
amount,  while  the  granules  are  much  fewer  and  are  now  confined 


Acnii  of  a  serous  salivary  gland. 
(Langley.) 
A,  resting  condition  ;   B,  discharged  con- 
dition. 


752  PHYSIOLOGY 

almost  entirely  to  the  inner  margin  of  the  cell.  Activity  is  thus 
associated  certainly  with  a  discharge  of  granules,  and  probably 
with  some  increased  building  up  of  protoplasm.  We  may  regard  the  act 
of  secretion  as  determined  by  the  alteration  of  the  granules  and  their 
discharge,  together  with  water  and  salts,  to  form  the  specific  secretion 
of  the  gland.  During  rest  the  granules  are  re-formed  by  precipitation 
in  or  modification  of  the  protoplasm  surrounding  the  nucleus.  We 
have  evidence  that  although  the  granules  form  the  secretion,  they 
represent,  not  the  secretion  itself,  but  a  precursor  of  some  at  any  rate 
of  its  constituents.     Thus  if  acetic  acid  be  added  to  the  sahva  obtained 


Fig.  328.     Sub-maxillary  gland  of  rabbit.     (Schafer  after  E.  MiiLLER.) 

The  cells,  all  serous,  are  in  different  functional  states :    a,  a  loaded  cell ; 

6,  a  discharged  cell ;  c,  a  secretory  canaliculus  penetrating  into  a  cell. 

from  the  sub-maxillary  gland,  the  mucin  is  precipitated  as  threads 
and  films.  If  the  granules  in  the  secreting  cells  also  consist  of  mucin 
we  should  expect  acetic  acid  to  have  a  coagulating  effect  upon  them. 
We  find,  on  the  contrary,  that  on  allowing  acetic  acid  to  flow  over 
a  section  of  the  fresh  gland  the  granules  at  once  swell  up  and  burst. 
We  must  regard  these  granules  therefore,  not  as  mucin,  but  as  a  pre- 
cursor of  mucin,  mucigen.  The  effect  of  ordinary  hardening  reagents, 
such  as  dilute  alcohol  up  to  70  per  cent,  or  Miiller's  fluid,  is  to  cause 
these  granules  to  swell  up  so  that  the  cells  become  filled  with  a  mass 
of  mucin  giving  the  typical  hyaline  appearance  of  ordinary  sections  of 
these  glands.  In  the  case  of  the  serous  gland  the  granules  (Fig.  328)  are 
apparently  protein  in  nature.  Where  ptyalin  is  a  constituent  of 
the  saliva  we  are  probably  justified  in  assuming  that  it  is  contained 
either  pre-formed  or  more  probably  as  a  precursor  in  the  granules. 
In  the  glands  of  the  stomach  we  have  evidence  that  the  granules  are 
not  pepsin — the  characteristic  ferment  of  gastric  juice — but  a  pre- 
cursor of  this  substance,  namely,  pepsinogen.     It  is  very  customary 


DIGESTION  IN  THE  MOUTH  753 

therefore  to  speak  of  the  granules  in  a  secreting  gland  as  zymogen 
granules,  i.e.  the  precursors  of  zymins  or  ferments.  It  is  probable 
that  we  ought  to  regard  these  granules  not  merely  as  material  pre- 
cursors of  the  constituents  of  the  secretion,  but  as  little  machines 
or  cell  laboratories  in  which  proceed  a  whole  series  of  chemical  and 
osmotic  changes  which  determine  the  production  of  the  fully  formed 
secretion  directly  from  the  protoplasm  and  indirectly  from  the 
ordinary  constituents  of  the  surrounding  lymph. 

From  an  examination  of  the  stained  specimens  of  glands  the 
following  stages  in  the  production  of  secretion  have  been  described  : 

(1)  In  the  neighbourhood  of  the  nucleus,  and  probably  with  its 


i5se*«. 


s    *    '  ■ 


Fig.  .329.    Cells  of  pancreas,  showing  successive  stages  in  activity,  a,  b,  c,  d. 
A,  resting;   D,  discharged  gland.      (Mathews.) 

active  co-operation,  a  differentiation  of  the  protoplasm  occurs  with 
the  production  in  most  cases  of  a  basophile  substance  which  in 
hardened  specimens  generally  takes  the  appearance  of  filaments. 
Since  these  filaments  are  sometimes  regarded  as  the  working  pait 
of  the  protoplasm,  they  have  been  given  the  name  of  ergastoplasm 
(Fig.  329,  c  and  d). 

(2)  By  a  modification  of  the  ergastoplasm  granules  are  formed.  After 
their  first  appearance  these  granules  undergo  gradual  modification,  as  is 
shown  by  the  fact  that  the  staining  reactions  of  the  granules  near 
the  base  of  the  cell  differ  from  those  of  the  granules  at  the  free  margin. 

(3)  When  the  secretion  is  excited,  the  fully  formed  granules 
take  up  water  and  salts  in  varying  proportions,  swell  up,  and  dis- 
charge their  contents  into  tJic  limien  of  the  alveolus  as  the  secretion 
proper  to  the  gland. 

ELECTRICAL  CHANGES 
Every  localised  chemical  cliange  in  a  system  permeated  by  electro- 
lytes  must   give   rise   to   electrical   differences   of   potential.     It    is 

48 


754  PHYSIOLOGY 

therefore  natural  that  electrical  changes  should  accompany  the 
intense  chemical  activity  which  is  associated  with  secretion.  The 
interpretation  of  these  changes  is  difficult,  owdng  to  the  simultaneous 
operation  of  another  factor  which  may  determine  electrical  differ- 
ences of  potential,  namely,  the  movement  of  fluids  through  porous 
membranes.  If  the  hilum  of  the  sub-maxillary  gland  and  its  outer 
surface  be  connected  with  a  galvanometer,  a  resting  difference  of 
potential  is  nearly  always  found,  generally  in  such  a  direction  that 
the  outer  surface  is  positive  to  the  hilum.  The  current  through  the 
gland  is  therefore  from  within  out.  On  exciting  the  chorda  tympani 
nerve  a  diphasic  effect  is  generally  obtained,  the  resting  difference 
being  first  increased  and  later  on  diminished.  On  excitation  of  the 
sympathetic  nerve  we  generally  obtain  a  purely  negative  variation 
of  the  resting  difference.  These  results  were  interpreted  by  Bayliss 
and  Bradford  as  due  to  the  co-operation  of  the  two  factors,  chemical 
change  in  the  gland- cells  and  movement  of  fluid  through  the  cells. 
The  positive  variation,  i.e.  the  current  from  within  out,  was  ascribed 
to  the  movement  of  fluid,  whereas  the  negative  variation  of  the 
resting  difference  was  thought  to  be  due  to  the  chemical  changes 
in  the  gland-cells. 

THE  SIGNIFICANCE  OF  THE  DOUBLE  NERVE-SUPPLY 
TO  THE  GLANDS 
According  to  Heidenhain,  although  the  parotid  gland  gives  little 
or  no  secretion  on  stimulation  of  the  sympathetic  nerve,  prolonged 
stimulation  of  this  nerve  causes  histological  changes  in  the  gland 
even  more  marked  than  those  produced  by  the  cranial  nerve.  Similar 
histological  changes  were  found  by  him  in  the  sub-maxillary  gland. 
He  was  therefore  led  to  put  forward  the  hypothesis  that  the  salivary 
glands  are  supplied  by  two  fundamentally  different  classes  of  fibres, 
namely  :  (1)  trophic  fibres,  which  determine  the  chemical  changes 
in  the  gland  responsible  for  the  production  of  the  specific  constituents 
of  the  secretion,  and  (2)  secreto-motor  fibres,  excitation  of  which 
causes  the  cells  to  take  up  water  and  salts  from  the  lymph  and  blood, 
and  pass  them  in  large  quantities  into  the  duct.  According  to  this 
view  the  sympathetic  nerve -supply  to  the  gland  would  consist  almost 
entirely  of  trophic  fibres,  whereas  secreto-motor  fibres  would  pre- 
dominate in  the  cranial  nerve-supply.  The  action  of  atropine  would 
appear  at  first  sight  to  favour  this  hypothesis.  In  minute  doses 
it  entirely  annuls  the  action  of  the  chorda  tympani  nerve  or  the 
corresponding  nerve  to  the  parotid,  while  it  is  without  effect  on 
the  sympathetic  nerve-supply  unless  given  in  huge  doses.  The  pre- 
ponderating effect  of  the  sympathetic  on  the  histological  structure 
of  the  gland-cells  has  not  been  confirmed  by  later    observers,  and 


DIGESTION  IN  THE  MOUTH  755 

there  is  no  doubt  that  the  characteristic  effects  of  stimulating  the 
chorda   tynipani,   namely,   the   profuse   secretion   of   watery   saliva, 
is  partly  due  to  the  simultaneous  large  supply  of  blood  to  the  gland. 
A  profuse  secretion  is  impossible  unless  there  is  a  facility  for  the 
gland  to  make  up  its  losses  in  fluid  at  the  expense  of  the  surrounding 
blood.     If  the  blood-supply  to  the  gland  be  diminished  during  stimu- 
lation of  the  chorda  tynipani,  as,  e.g.  by  clamping  the  carotid  artery 
or  by  bleeding  the  animal,  there  is  an  actual  diminution  in  the  total 
amount  of  secretion  and  a  relative  increase  in  the  proportion  of 
solids  it  contains.     It  is  not  easy,  however,  to  imitate  exactly  in 
this  way  the  effects  of  excitation  of  the  sympathetic.     On  the  whole, 
we  may  probably  assume  with  Langley  that  the  evidence  in  favour 
of  the  existence  of  two  kinds  of  secretory  fibres  is  insufficient  and  that 
the  different  results  obtained  on  exciting  the  two  sets  of  nerve  fibres 
is,  largely  at  any  rate,  conditioned  by  the  simultaneous  changes  pro- 
duced by  these  nerves  on  the  circulation  through  the  gland.     The 
varying  effects  of  atropine  on  the  two  classes  certainly  indicate  a 
difference  in  the  mode  of  nerve-ending  of  the  two  sets  of  fibres,  but 
this  conclusion  does  not  necessarily  involve  the  conclusion  that  the 
influence  of  the  sympathetic  and  of  the  chorda  tynipani  respectively 
on  the  gland-cells  is  also  different. 

THE  ENERGY  INVOLVED  IN  THE  ACT  OF  SECRETION 
The  source  of  the  energy  must  be  sought  in  the  processes  of  oxida- 
tion occurring  in  the  cells  of  the  gland,  and  Barcroft  has  attempted 
to  determine  the  total  amount  of  energy  put  out  by  the  gland  in  the 
act  of  secretion  by  measuring  its  respiratory  exchanges  under  the 
conditions  of  rest  and  activity.  He  found  that  the  resting  subr_ 
maxillary  gland  in  a  small  dog  took  up  0-25  c.c.  of  oxygen  per  minute 
and  put  out  0-17  c.c.  COg,  while  during  active  secretion  it  absorbed 
0-8G  c.c.  0.^  and  gave  off  0-39  c.c.  CO^.  Assuming  that  the  total  oxygen 
taken  up  is  employed  in  the  oxidation  of  a  food  substance,  such  as 
glucose,  and  that  the  whole  of  the  energy  of  the  chemical  changes  is 
set  free  in  the  form  of  heat,  we  find  that  a  resting  gland  weighing 
about  six  grammes  produces  about  1-1  calories  per  minute.  We  know, 
however,  that  a  certain  amount  of  external  work  is  performed  in  the 
secretion  of  a  saliva  containing  less  salts  than  the  original  blood, 
and  also,  when  there  is  any  resistance  to  the  flow  of  saliva  through 
the  duct,  in  raising  the  hydrostatic  pressure  of  the  saliva  in  the  duct 
to  a  height  greater  than  that  in  the  blood  capillaries. 

Can  we  from  all  these  data  form  a  conception  of  the  total  changes 
occurring  in  the  gland  and  involved  in  the  formation  of  the  secretion  ? 
Even  during  rest,  changes  are  going  on  in  the  gland-cells,  chaiijjes 
which  involve  the  taking  up  of  food  material  and  its  assimilation 


756  PHYSIOLOGY 

under  the  influence  of  the  nucleus,  perhaps  into  the  nucleus  itself, 
and  certainly  into  the  undifferentiated  cytoplasm.  In  this  cytoplasm 
a  further  change  occurs,  leading  to  its  transformation  into  gxanules. 
When  activity  is  excited  by  the  stimulation  of  secretory  nerves, 
the  primary  change  appears  to  involve  simply  the  granules.  These 
structures  must  absorb  water,  apparently  against  osmotic  pressure. 
Those  nearest  the  lumen  swell  up,  become  converted  into  spheres 
containing  water  and  salts  in  smaller  proportion  than  exists  in  the 
lymph  bathing  the  cells  (and  presumably  in  the  protoplasm  sur- 
rounding the  granules),  and  in  this  swollen  form  are  discharged  or 
ruptured  on  the  periphery  of  the  cell  into  the  lumen,  so  giving  rise 
to  secretion.  This  discharge  of  a  fluid  with  a  smaller  molecular 
concentration  than  the  cell  or  surrounding  blood  plasma  must  lead 
to  an  increased  concentration  in  the  remaining  parts  of  the  cell. 
The  increased  concentration  would  naturally  induce  a  flow  of  water 
from  lymph  into  cell,  and  the  consequent  concentration  of  the  lymph 
would  in  the  same  way  cause  a  flow  of  water  from  blood  to  lymph. 
This  pull  of  water  by  the  cell  from  the  blood  is  still  further 
increased  in  another  way.  The  act  of  secretion,  involving  as 
it  does  the  expenditure  of  energy,  can  be  carried  out  only  at 
the  expense  of  chemical  changes  in  the  cell.  These  chemical  changes, 
as  in  all  other  metabohc  processes  of  the  body,  will  result  in  the 
formation  of  a  number  of  small  molecules  from  the  great  colloid 
molecules  of  the  protoplasm.  The  products  of  metabolism,  or 
metabolites,  will  therefore  accumulate  in  the  cell,  pass  into  the  lymph, 
and  increase  the  concentration  of  the  latter.  The  increased  con- 
centration will  call  forth  an  increased  transudation  of  fluid,  e.g.  water, 
from  the  blood-vessels,  and  the  transudation  thus  evoked  will  be 
greater  than  that  necessary  to  provide  the  water  of  the  saliva,  and 
will  therefore  produce  a  distension  of  the  lymphatic  spaces  of  the 
gland  and  an  increased  discharge  of  lymph  along  its  efferent  lym- 
phatics. As  a  secondary  result  of  the  activity,  perhaps  in  con- 
sequence of  the  removal  of  the  products  of  the  resting  metabolism 
of  the  gland,  there  is  increased  growth  of  protoplasm,  increased 
activity  of  the  nucleus,  and  therefore  a  tendency  to  increased  assimi- 
latory  changes  and  a  preparation  of  the  cell  for  further  secretory 
changes  either  immediately  or  hereafter. 

In  the  gland,  however,  as  in  muscle,  when  we  attempt  to  form 
a  conception  of  the  mechanism  of  the  chemical  machine  in  the 
living  cell,  '^  we  are  brought  up  against  insuperable  difficulties. 
One  might  ^  perhaps  conceive  of  the  secretory  granules  being 
bounded  by  a  membrane  impermeable  to  intermediate  metabohtes 
and  salts,  but  permeable  to  carbon  dioxide.  If  the  first  effect  of 
stimulation  of  the  secretory  nerves  were  to  produce  an  explosive 


DIGESTION  IN  THE  MOUTH  757 

disintegration  of  the  complex  molecules  making  up  the  granules, 
we  should  have  a  sudden  multiplication  of  molecules  within  the 
granules.  This  would  cause  a  large  rise  of  the  osmotic  pressure 
in  these  granules  and  the  consequent  absorption  of  water  from  the 
surrounding  protoplasm.  This  process,  however,  could  only  result 
in  the  production  of  a  fluid  in  the  granules  having  the  same  osmotic 
pressure  as  the  surrounding  medium,  whereas  we  know  that  saliva 
has  a  molecular  concentration  which  is  only  one  half  of  that  of  the 
blood  or  lymph.  We  should  therefore  have  to  make  a  second  assump- 
tion, namely,  that,  before  the  extrusion  of  the  solution  from  the 
granules,  there  is  a  further  breakdown  of  the  metabolites  by  a  process 
of  oxidation,  with  the  production  of  carbon  dioxide  which  diffuses 
into  the  surrounding  protoplasm.  We  have,  however,  no  evidence 
of  either  of  these  processes  or  for  any  of  these  assumptions,  and 
I  have  only  adduced  them  in  order  to  show  how  far  we  are  still  from 
the  actual  comprehension  of  the  events  occurring  in  every  living 
cell,  and  underlying  its  conditions  of  rest  and  activity. 


SECTION   II 

THE  PASSAGE   OF  FOOD  FROM  THE  MOUTH 
TO  THE  STOMACH 

The  food  after  mastication  is  carried  to  the  stomach  by  a  complex 
series  of  co-ordinated  movements  involving  the  muscles  of  the  pharynx 
and  the  oesophagus  (Fig.  330).     Various  methods  have  been  used  to 


Fig.  330.  Dissection  to  show  muscles  employed  in  deglutition. 
b,  styloid  process,  from  which  arise  1,  the  styloglossus,  2,  the  stylohyoid, 
3,  the  stj'lo-pharyngeus  muscles  ;  c,  section  of  lower  jaw  ;  d,  hyoid  bone  ; 
e,  thyroid  cartilage  ;  g,  isthmus  of  thyroid  gland  ;  4,  cut  edge  of  mylohj'oid 
muscle  ;  5,  6,  7,  8,  muscles  of  tongue  ;  9,  10,  1 1,  superior,  middle,  and  inferior 
constrictors  of  pilar jTix  ;    12.  oesophagus.     (Allen  Thomson.) 

study  the  process  of  deglutition  in  man  and  the  higher  animals. 
Important  information  can  be  obtained  by  allowing  a  man  or  animal 
to  swallow  either  a  fluid  or  solid  with  which  bismuth  is  mixed  and 
observing  the  passage  of  the  opaque  substance  under  the  Rontgen 

758 


PASSAGE  OF  FOOD  FROM  MOUTH  TO  STOMACH      759 

rays.  The  subnitrate  of  bismuth  may  be  mixed  with  milk  for  a 
fluid  or  with  bread  and  milk  for  a  semi-sohd  substance,  or  may  be 
enclosed  in  a  cachet  and  swallowed  as  a  solid  bolus.  The  time  of 
entry  of  the  food  into  the  stomach  may  be  determined  by  auscultatinfj 
with  a  stethoscope  over  the  region  of  the  cardiac  orifice.  Since 
a  certain  amount  of  air  is  always  swallowed  at  the  same  time  as  the 
food,  the  escape  of  this  air  through  the  small  cardiac  orifice  gives 
rise  to  a  bubbling  noise  which  can  be  easily  heard.  In  the  horse 
the  movement  of  a  bolus  down  the  oesophagus  can  be  seen  or  felt 
from  the  outside  of  the  neck.  The  relative  time-relations  of  the 
events  at  different  parts  of  the  oesophagus  may  be  obtained  by  passing 
sounds  provided  with  rubber  balloons  to  different  levels  in  the  tube 
and  connecting  these  sounds  %vith  recording  tambours  or  piston 
recorders.  This  method  has  been  employed  both  in  men  and  in 
animals. 

When  a  mouthful  of  water  is  taken  two  sounds  may  be  heard 
on  auscultating  over  the  oesophagus.  The  first  sound  immediately 
follows  the  beginning  of  the  act  of  swallowing  and  is  probably  due  to 
the  impact  of  the  fluid  against  the  posterior  pharyngeal  wall  brought 
about  by  the  sudden  contraction  of  the  mylohyoid  and  other  muscles 
which  throw  the  fluid  from  the  back  of  the  tongue  across  the  pharynx. 
The  second  sound  is  heard  best  by  hstening  over  the  epigastrium. 
It  begins  from  four  to  ten  seconds  after  the  first  sound,  and  lasts 
for  two  or  three  seconds.  The  interval  between  the  two  sounds  is 
not  constant,  and  may  vary  in  the  same  individual.  If  the  observa- 
tion be  carried  out  on  a  man  l}nng  on  his  back,  the  trickling  second 
sound  is  changed  into  a  series  of  sounds  which  have  been  described 
as  squirts,  which  vary  from  two  to  five  in  number,  each  lasting  about 
one  second.  The  second  sound  may  be  absent  when  a  sohd  bolus 
is  swallowed.  On  observing  the  process  by  Rontgen  rays  very 
much  the  same  time-relations  are  obtained.  If  a  mouthful  of  milk 
iiiixtMl  with  bismuth  carbonate  be  swallowed,  it  will  be  seen  passing 
rapidly  down  the  ocsophagiis  to  the  cardiac  orifice  of  the  stomach. 
Here  the  passage  becomes  slow,  and  the  fluid  escapes  slowly  in  a 
narrow  stream  into  the  stomacli.  The  average  time  which  elapses 
between  the  beginning  of  deglutition  and  the  disappearance  of  the 
last  trace  of  fluid  from  the  oesophagus  is  about  six  seconds.  The 
same  course  of  events  is  induced  when  the  food  swallowed  is  semi- 
sohd.  If,  however,  the  bolus  be  dry,  such  as  a  cachet  of  bismuth 
carbonate,  it  may  pass  down  the  oesophagus  with  extreme  slowness 
and  may  take  as  much  as  fifteen  minutes  to  reach  the  cardiac 
orifice,  although  the  individual  who  has  swallowed  it  is  quite  unaware 
of  its  continued  presence  in  the  oesophagus.  If,  as  would  normally 
be  the  case,  the  cachet  be  well  moistened  with  saliva  or  water  before 


760  PHYSIOLOGY 

swallowing,  it  passes  much  more  rapidly,  the  total  time  taken  being 
between  eight  and  eighteen  seconds. 

It  has  been  customary  since  the  time  of  Magendie  to  divide  the 
act  of  swallowing  into  three  stages,  during  the  first  of  which  the 
bolus  of  food  is  carried  past  the  anterior  pillars  of  the  fauces ;  during 
the  second  through  the  pharynx,  past  the  openings  of  the  nasal 
cavities  and  of  the  larynx ;  and  during  the  third  through  the  oeso- 
phagus into  the  stomach.  There  is,  however,  no  pause  between  these 
various  stages.  The  act  of  deglutition  is  one,  and  the  initiation 
of  the  first  stage  inevitably  involves  the  completion  of  the  third. 
The  food  is  masticated,  and  is  collected  as  a  bolus  on  the  dorsum 
of  the  tongue.  A  pause  then  takes  place  in  the  movements  of  mastica- 
tion, a  sUght  movement  of  the  diaphragm  usually  occurs  known  as 
'  respiration  of  swallowing,'  and  then  a  sudden  elevation  of  the 
tongue  throws  the  bolus  back  through  the  anterior  pillars  of  the 
fauces.  In  this  movement  the  chief  factor  is  the  contraction  of 
the  mylohyoid  muscle,  which  presses  the  tongue  against  the  palate 
and  pushes  it  backwards.  The  backward  movement  of  the  tongue  may 
also  be  aided  by  the  contraction  of  the  styloglossus  and  palatoglossus 
muscles  which  pull  the  base  of  the  tongue  suddenly  backwards. 
These  muscles,  especially  the  palatoglossi,  serve  to  close  the  isthmus 
faucium,  thus  preventing  any  return  of  the  food  towards  the  mouth. 

As  the  food  is  passing  through  the  upper  part  of  the  pharynx  it 
traverses  a  region  common  to  the  respiratory  as  well  as  the  digestive 
passages.  Its  passage  through  this  region  is  therefore  rapid,  and 
is  associated  with  a  closure  of  the  two  openings  of  the  air  passages 
into  the  pharynx.  The  nasal  cavity  is  shut  off  by  a  simultaneous 
contraction  of  the  levator- palati  and  palato-pharyngeus  muscles  and 
azygos  uvulae,  by  which  means  the  soft  palate  is  raised  (Fig.  331)  and 
the  posterior  pillars  are  proximated  to  the  uvula.  The  upper  and  back 
wall  of  the  palate  is  thus  formed  into  a  tense  sloping  roof  which  guides 
the  bolus  down  the  pharynx. 

More  important  is  the  shutting  off  of  the  lower  air  passages. 
The  contraction  of  the  mylohyoid  muscles  which  initiate  deglutition 
is  followed  almost  immediately  (at  an  interval  of  0-47  sec.)  by 
an  elevation  of  the  larynx,  and  this  elevation  is  accompanied  by 
closure  of  the  glottis  as  well  as  of  the  superior  opening  of  the  larynx. 
The  laryngeal  opening  is  bounded  in  front  by  the  epiglottis,  behind 
by  the  tips  of  the  arytenoid  cartilages,  and  at  the  sides  by  the  aryteno- 
epiglottidean  folds.  When  deglutition  takes  place  the  arytenoid 
cartilages,  which  normally  lie  against  the  posterior  wall  of  the  pharynx, 
are  rotated  and  move  inwards  and  forwards,  so  that  the  laryngeal 
opening  assumes  the  form  of  a  tri-radiate  fissure,  the  vertical  limb 
being  short,  while  the  transverse  limb  is  rounded  owing  to  the  pulling 


PASSAGE  OF  FOOD  FROM  MOUTH  TO  STOMACH      761 

inwards  of  the  margins  of  the  epiglottis.  At  the  same  time  both 
the  true  and  false  vocal  cords  are  approximated,  while  the  movement 
of  the  dorsmn  of  the  tongue  backwards  enables  the  closed  laryngeal 
orifice  to  lie  directly  under  the  back  part  of  the  tongue.  The  muscles 
which  are  actively  involved  in  this  closure  of  the  lower  air  passages 
are  the  external  thyro-arytenoid,  arytenoid,  ary-epiglottidean,  and 
the  lateral  crico-arytenoid  muscles.  Since  the  approximation  of  the 
posterior  to  the  anterior  boundary  of  the  laryngeal  opening  is  only 
rendered  possible  by  the  elevation  of  the  whole  larynx  under  the 


^r 


v^ 


Fig.  331.     Diagram  (after  Tigerstedt)  to  show  the  position  of  the  soft  palate. 
I,  (luring  rest ;   II,  during  the  act  of  swallowing. 


hyoid  bone,  the  act  of  deglutition  cannot  be  carried  out  unless  the 
larynx  is  free  to  move. 

The  two  openings  from  the  back  of  the  pharynx  into  the  air 
passages  being  thus  closed,  the  bolus  is  shot  rapidly  past  them  into 
the  region  of  the  middle  and  inferior  constrictors  of  the  pharynx. 
If  the  bolus  be  liquid  or  semi-fluid,  the  movement  of  the  back  part 
of  the  tongue  may  be  sufficient  to  propel  the  substance  past  the 
constrictors  through  the  lax  oesophagus  to  its  lower  end.  It  is  on 
this  account  that,  when  corrosive  fluids  are  swallowed  by  accident, 
we  very  often  find  the  damage  to  the  oesophagus  limited  to  the  three 
points  where  it  is  narrowed  and  where,  therefore,  there  is  a  slight 
hindrance  to  the  onward  flow  of  fluid.  If  the  bolus  be  large  and 
solid  or  semi-solid,  it  is  seized  in  the  grasp  of  the  middle  constrictors 
on  passing  through  the  upper  part,  of  the  pharynx,  and  is  thrust 
bv    successive    contractions    of    this    muscle    and    of    the    inferior 


762 


PHYSIOLOGY 


constrictor  gradually  down  the  oesophagus.  The  walls  of  the  cervical 
part  of  the  oesophagus  are  composed  of  striated  muscle.  In  the 
thorax  striated  and  unstriated  muscles  are  associated  together, 
while  the  lower  third,  in  the  neighbourhood  of  the  stomach,  consists 
almost  entirely  of  imstriated  muscle.  Corresponding  to  these  differ- 
ences in  structiu-e,  Kronecker  and  Meltzer  have  found  differences 
in  the  duration  and  rapidity  of  propulsion  of  the  contractional  waves 
in  each  part.  The  following  Table  shows  the  time -relations  of  the 
chief  muscles  engaged  in  deglutition  as  determined  by  Kronecker 
and  Meltzer  and  bv  Marckwald  : 


Time  from 
commencement 

Interval 

Muscle  movcnipnt 

Duration  of 
contraction 



Mylohyoid 

0-6  sec. 



0-03  sec. 

Eespiration  of  swallowiig 

— 

— 

0-07  sec. 

Elevation  of  larjTix 

0-8  sec. 

0-3  sec. 

0-2  sec.  - 

Constrictors  of  pharjTix 

1-0  to  2-0  sec. 

— 

0-9  sec. 

First  section  of  oesophagus 

2-0  to  2-5  sec. 

.3-0  sec. 

1-8  sec. 

Second  section  of  a?sophagus 

6-0  to  7-0  sec. 

6-0  soc. 

3-0  sec. 

Third  section  of  oesophagus 

about  10  sec. 

The  free  passage  of  food  down  the  oesophagus  under  the  influence 
of  the  propulsive  force  exercised  by  the  mylohyoid  muscles  shows 
that  the  walls  of  this  tube  must  be  lax,  and  in  fact  one  must  assume 
that  the  first  act  of  deglutition,  so  far  as  concerns  the  oesophagus, 
is  an  inhibition  initiated  reflexly  with  the  beginning  of  the  act  of 
deglutition.  When  a  second  act  of  deglutition  succeeds  the  first 
\vdthin  a  sufficiently  short  interval,  the  reflex  inhibition  due  to  the 
second  act  may  prevent  the  development  of  any  wave  of  contraction 
in  the  oesophagus.  This  tube  thus  remains  in  a  lax  condition  and 
allows  the  free  rapid  passage  of  the  food  downwards  until  the  move- 
ments of  deglutition  have  come  to  an  end,  when  a  peristaltic  con- 
traction occurs  and  sweeps  all  remaining  adherent  particles  of  food 
into  the  stomach.  The  circular  fibres  of  the  lower  end  of  the 
oesophagus  which  form  the  cardiac  sphincter  of  the  stomach  are 
normally  in  a  state  of  tonic  contraction.  When  one  mouthful  of 
food  is  swallowed  it  may  be  either  squirted  directly  into  the  stomach, 
or  may  remain  at  the  lower  end  of  the  oesophagus  until  the  following 
peristaltic  wave  forces  it  through  the  orifice.     When  several  acts  of 


PASSAGE  OF  FOOD  FROM  MOUTH  TO  STOMACH      703 

deglutition  succeed  one  another,  the  cardiac  sphincter  shares  in  the 
inhibition  of  the  oesophageal  walls,  and  offers  no  resistance  to  the 
direct  propulsion  of  food  from  the  month  to  the  stomach. 


Fig.  ;j32.  Curves  obtained  during  swallowing  by  placing  two  rubber  balloons,  one 
(the  upper  curve)  in  the  pharj-nx,  the  other  (lower  curve)  in  the  oesophagus. 
In  A  the  second  balloon  was  4  cm.  ;  in  B  12  cm.  ;  and  in  c  16  cm.  from 
the  upper  end  of  the  oesophagus.  In  each  curve  it  will  be  noticed  that  the 
excursion  of  the  upper  lever  is  followed  immediatdy  by  an  excursion  of  the 
lower  lever  (due  to  passage  of  the  swallowed  fluid  and  transmitted  rise  of 
pressure),  and  then,  after  an  interval  of  time  varying  with  the  distance  between 
the  balloons,  by  another  rise  due  to  the  peristaltic  contraction  of  the  wall  of 
the  oesophagus. 

THE  NERVOUS  MECHANISM  OF  DEGLUTITION 
Deglutition  is  a  reflex  act.  When  we  swallow  voluntarily  we 
supply  the  necessary  initial  stimulus  either  by  touching  the  fauces 
with  the  tongue  or  by  forcing  a  certain  amount  of  sahva  into  the 
fauces.  The  afferent  channels  of  the  reflex  arc  contained  in  the 
second  division  of  the  fifth  nerve,  the  glossopharyngeal  nerve,  and 


764  PHYSIOLOGY 

the  pharyngeal  branches  of  the  superior  laryngeal  nerve.  We  can 
excite  a  single  act  or  a  whole  series  of  acts  of  deglutition  by  electrical 
stimulation  of  the  central  end  of  the  last-named  nerve.  The  efferent 
fibres  which  determine  the  contraction  of  muscles  engaged  in  the 
act  of  deglutition  travel  by  the  hypoglossal  nerve  to  the  muscles 
of  the  tongue,  by  the  fifth  to  the  mylohyoid,  by  the  glossopharyngeal, 
the  vagus,  and  the  spinal  accessory  nerves  to  the  muscles  of  the  fauces 
and 'pharynx.  The  closure  of^he  larynx  is  effected  by  impulses  which 
travel  through  the  superior  and  inferior  laryngeal  branches  of  the 
vagus.     The  centre  for  the  act  is  situated  in  the  medulla  oblongata. 


Fig.  333.     Tracings  of  respiratory  movements  to  show  effect  of  stimulating  the 

central  end  of  the  glossopharyngeal  nerve.     (Mabckwald.) 

The  point  of  stimulation  is  marked  with  a  cross.     Note  that  the  stoppage 

may  occur  at  any  phase  of  the  respiratory  movement. 

and  can  be  considered  as  consisting  of  a  chain  of  centres  stimulation  of 
one  of  which  involves  the  firing  off  of  all  the  others  in  orderly  sequence. 
Thus,  as  Meltzer  has  shown,  the  propulsion  of  the  contraction  down 
the  oesophagus  is  determined  by  the  intracentral  nervous  connections, 
and  does  not  require  the  integrity  of  the  muscular  tube  itself.  If 
the  oesophageal  nerves  be  divided,  the  act  of  deglutition  is  abolished, 
the  upper  part  of  the  oesophagus  becoming  permanently  relaxed, 
while  the  lower  part,  including  the  cardiac  sphincter,  enters  into 
a  state  of  tonic  contraction.  On  the  other  hand,  the  oesophagus 
may  be  ligatured  or  cut  across  without  interfering  with  the  propulsion 
of  the  wave  of  contraction,  started  in  the  pharynx,  from  one  end  of 
the  tube  to  the  other.  Stimulation  applied  to  the  mucous  surface 
of  the  oesophageal  tube  is  without  effect. 

There  is  an  important  interdependence  between  the  functions 
of  respiration  and  deglutition.  If  an  inspiratory  or  expiratory 
movement  were  going  on  during  the  act  of  deglutition,  food  might 


PASSAGE  OF  FOOD  FROM  MOUTH  TO  STOMACH     765 

be  drawn  into  the  lungs  or  driven  into  the  nasal  cavities.  Such 
an  accident  is  prevented  by  the  fact  that  every  act  of  swallowing 
inhibits  a  respiratory  movement.  This  inhibition  is  effected  reflexly 
through  the  glossopharyngeal  nerve.  Stimulation  of  the  central 
end  of  this  nerve  at  once  causes  cessation  of  respiration  in  whatever 
phase  it  may  happen  to  be  (Fig.  333).  This  cessation  lasts  for  five  or 
six  seconds,  i.e.  a  sufficient  length  of  time  for  a  whole  series  of  acts 
of  deglutition.  Respiration  then  recommences,  and  the  inhibition 
cannot  be  prolonged  by  continuing  the  stimulation  of  the  glosso- 
pharyngeal nerve.  This  inhibition  of  the  activity  of  the  respiratory 
centre  can  be  shown  on  oneself.  If  the  breath  be  held  until  the 
feeUng  of  dyspnoea,  i.e.  the  need  to  breathe,  becomes  insistent,  relief 
is  at  once  experienced  by  swallowing,  and  the  feeling  of  relief  will 
last  for  three  or  four  seconds. 


SECTION  111 
DIGESTION  IN  THE  STOMACH 

GASTRIC  JUICE 

Within  five  minutes  of  the  taking  of  food  into  the  mouth  a  secre- 
tion of  gastric  juice  begins  from  the  multitude  of  tubular  glands 
which  make  up  the  greater  part  of  the  mucous  membrane  of  the 
stomach.  As  the  food,  masticated  and  thoroughly  mixed  with 
sahva,  is  swallowed  in  successive  portions,  it  accumulates  in  a  mass 
in  the  fundus  of  the  stomach,  and  the  mass  thus  formed  is  penetrated 
with  difficulty  by  the  juice  which  is  continually  being  poured  out 
by  the  walls  of  the  stomach,  so  that  safivary  digestion  can  be  con- 
tinued for  a  considerable  time. 

The  gastric  juice,  which  is  so  poured  out,  can  be  obtained  in 
various  ways,  most  of  them  yielding  it  mixed  more  or  less  with  the 
food-stuffs.  In  cHnical  practice  it  is  the  custom  to  give  a  definite 
meal,  and  then  at  a  given  interval  after  the  meal  to  wash  out  the 
stomach,  so  obtaining  a  mixture  of  gastric  juice  and  partially  digested 
food. 

A  method  of  obtaining  the  juice  in  a  perfectly  pure  condition 
has  been  devised  by  Pawlow.  A  case  had  been  previously  described 
by  Richet  in  which,  as  the  result  of  the  accidental  taking  of  a  corrosive 
alkali,  the  oesophagus  had  become  completely  occluded  by  the  cica- 
trisation of  the  ulcer  produced.  In  order  to  preserve  the  individual 
from'starvation,  it  was  necessary  to  perform  gastrostomy,  i.e.  to  make 
an  ^artificial  opening  into  the  stomach  through  which  he  could  be 
fed.  Although  in  this  patient  the  passage  of  the  sahva  from  mouth 
to  stomach  was  completely  prevented,  it  was  observed  that  merely 
taking  food  into  the  mouth  was  followed  by  the  secretion  of  gastric 
juice.  Pawlow  produced  this  condition  artificially  in  dogs.  The 
oesophagus  was  divided  and  the  two  ends  brought  to  the  surface 
of  the  neck.  At  the  same  time  an  opening  was  made  into  the  stomach. 
The  animals  could  be  fed  either  through  the  opening  of  the  oesophagus 
in  the  neck,  or  with  soHd  food  through  the  gastric  fistula.  They 
could  also  eat  and  swallow  food  as  usual,  but  the  food  thus  swallowed 
simply  fell  out  of  the  opening  in  the  neck  without  passing  into  the 
stomach.  Under  these  circumstances  it  is  found  that  the  taking  of 
food  is  quickly  followed  by  a  secretion  of  gastric  juice,  which  can  be 

766 


DIGESTION  IN  THE  STOMACH  767 

collected  in  vessels  connected  with  the  fistulous  opening.  If  taken 
from  a  fasting  animal,  such  a  juice  is  perfectly  free  from  admixture, 
and  can  be  regarded  as  pure  gastric  juice.  It  is  quite  clear,  strongly 
acid,  without  smell.  It  contains  about  0-3  to  0-6  per  cent,  total  solids  ; 
it  contains  no  peptone,  but  traces  of  protein.  The  following  Table 
represents  its  average  composition  : 

Hydrochloric  acid         .  .  .  0-46  to  0-58  per  cent. 

Chlorine 0-49  to  0-62       „ 

Total  solids  ....  0-43  to  0-60      „ 

Ash 0-09  to  0-lC      „ 

If  the  juice  be  allowed  to  stand  in  the  ice  chest  for  a  day  it  becomes 
cloudy  and  deposits  a  fine  granular  precipitate,  which  apparently 
represents  the  active  agent  of  the  juice,  and  may  perhaps  be  regarded 
as  pepsin  in  a  pure  form. 

The  actions  of  gastric  juice  are  due  partly  to  the  acid,  partly 
to  the  combined  action  of  the  acid  and  the  ferments.  The  acid 
of  the  gastric  juice,  when  obtained  free  from  admixture,  is 
entirely  hydrochloric  acid.  Dog's  juice  contains  on  the  average 
about  0-6  per  cent.  HCl ;  human  gastric  juice  probably  contains 
less,  about  0-2  per  cent.  When,  however,  we  examine  the  gastric 
contents,  composed  of  a  mixture  of  gastric  juice  and  semi- digested 
food,  we  always  find,  besides  the  hydrochloric  acid,  other  acids  present, 
among  which  the  most  prominent  is  lactic  acid.  So  constantly 
is  this  latter  acid  present  that  it  was  formerly  thought  by  some 
physiologists  to  be  the  chief  acid  of  the  gastric  juice.  It  is  produced 
by  processes  of  fermentation  occurring  in  the  food.  Whenever  we 
take  carbohydrates  we  swallow  at  the  same  time  micro-organisms, 
and  these  in  the  warm  moist  mass  quickly  attack  the  carbohydrates, 
converting  them  into  sugar  and  then  into  lactic  acid.  As  the  gastric 
juice  gradually  soaks  into  the  food  and  renders  it  acid,  it  stops  this 
lactic  acid  fermentation,  so  that  whereas  in  the  early  stages  of 
gastric  digestion  both  acids  are  present  in  considerable  quantity, 
towards  the  end  of  gastric  digestion  lactic  acid  is  almost  entirely 
absent. 

In  some  pathological  cuiiditions  free  liydrocliloric  acid  may  be  entirely  wanting 
from  the  gastric  juice,  and  the  detection  of  tliis  acid  in  gastric  juice  becomes 
therefore  a  matter  of  con.siderable  clinical  importance.  For  this  purpose  we  can 
employ  various  indicators,  which  change  colour  in  the  presence  of  a  free  strong 
acid  such  as  HCl,  but  are  unaffected  by  weak  acids  such  as  lactic  acids,  or  the  fatty 
acids.  Chief  among  these  indicators  are  Congo  red,  which  turns  blue  with  mineral 
acids,  and  a  slaty  colour  with  lactic  acid  ;  and  tropaolin  00,  whicli  turns  a 
brilliant  red  in  the  presence  of  a  free  mineral  acid,  but  is  unaltered  bj-  lactic  acid. 
The  reagent  which  is  most  employed  is  Gunzberg's  reagent.  This  is  a  mixture 
of  phloroglucin  and  vanillin  dissolved  in  absolute  alcohol.  A  drop  of  tliis  is 
evaporated  to  dryness  in  a  porcelain  capsule      A  ilrop  of  the  tluid  suspected  to 


768  PHYSIOLOGY 

contain  free  acid  is  then  added,  and  also  evaporated  to  dryness.  If  free  HCl 
be  present,  the  residue  on  drying  becomes  a  briUiant  red  colour,  an  effect  which 
is  not  produced  by  the  presence  of  free  lactic  or  free  fatty  acids. 

Great  stress  has  been  laid  on  the  determination  of  the  actual 
amount  of  free  H  ions  present,  and  for  this  purpose  the  acidity  of 
gastric  juice  or  of  digestive  mixtures  has  been  tested  by  determining 
its  inverting  power  on  cane  sugar,  or  its  power  to  hasten  the  saponi- 
fication of  ethyl  acetate.  The  acidity  estimated  in  this  way  is 
diminished  considerably  by  the  presence  of  albumens,  and  still  more 
by  the  presence  of  albumoses  or  peptones.  But  it  does  not  seem 
that  the  adjuvant  action  of  the  acid  on  the  proteolytic  powers  of 
the  gastric  ferment  is  in  any  way  affected  by  the  diminution  of  its 
acidity  causad  by  the  presence  of  peptone.  The  coloured  indicators 
mentioned  above,  however,  serve  as  trustworthy  indications  of  the 
amount  of  free  acid  present,  considered  with  regard  to  its  digestive 
functions. 

In  order  to  determine  quantitatively  the  amount  of  free  HCl,  the  follow- 
ing procedure  is  employed  (Morner  and  Sjoqvist):  Ten  cubic  centimetres  of 
the  gastric  juice  are  neutralised  with  barium  carbonate  (Utmus  being  employed 
as  an  indicator).  The  mixture  is  dried  in  a  platinum  dish,  incinerated,  and 
the  ash  extracted  with  warm  water  and  filtered.  In  this  process  the  organic 
acids  are  destroyed  and  converted  into  barium  carbonate.  The  solution  there- 
fore contains  merely  the  barium  which  was  taken  up  to  combine  with  the  free  HCl. 
Estimation  of  the  barium  in  the  filtrate  gives  the  amount  of  BaCl2  present,  and 
therefore  the  amount  of  hydrochloric  acid  in  the  gastric  juice.  The  barium  is 
determined  by^  titrating  in  presence  of  sodium  acetate  and  acetic  acid  with 
potassium  bichromate  solution,  '  tetra  papier  '  being  used  as  an  indicator.  This 
turns  deep  blue  in  the  presence  of  free  bichromate  in  solution. 

THE  ACTIONS  OF  GASTRIC  JUICE  ON  FOOD-STUFFS 
By  the  action  of  the  hydrochloric  acid  certain  changes  are  induced 
in  the  food-stuffs.  Cane  sugar  is  inverted  to  glucose  and  fructose  ; 
some  proteins,  such  as  blood  fibrin,  are  swollen  up  to  form  a  jelly-like 
mass.  The  caseinogen  of  milk  is  precipitated,  the  collagen  of  the 
connective  tissues  is  swollen  up.  It  is  possible  that  a  certain  small 
amount  of  hydrolysis  also  takes  place  in  the  dextrins  and  maltose 
produced  by  the  action  of  ptyalin  on  starch. 

The  chief  digestive  function  of  the  gastric  juice  is  dependent 
on  the  action  of  the  ferment  pepsin.  This  substance,  which  is 
inactive  in  neutral  medium,  needs  the  co-operation  of  an  acid,  hydro- 
chloric acid  being  the  most  effective,  though  its  place  may  be  taken 
by  phosphoric,  sulphuric,  or  lactic  acid.  Its  main  effect  is  on  the 
proteins  of  the  food.  The  stages  in  its  action  may  be  best  studied 
by  taking  as  an  example  its  action  on  blood  fibrin.  If  fibrin  be 
immersed  in  0-4  per  cent,  hydrochloric  acid,  it  swells  up  to  a  gelatinous 
mass.     On  then  stirring  in  an  extract  of  gastric  mucous  membrane, 


DIGESTION  IN  THE  STOMACH 


769 


or  any  preparation  of  pepsin,  the  gelatinous  mass  rapidly  undergoes 
solution.  If  the  mixture  be  boiled  and  neutralised,  immediately 
after  solution  has  occurred,  nearly  the  whole  of  the  protein  is  thrown 
down  in  a  coagulated  form.  The  first  effect  therefore  is  the 
production  of  coagulable  soluble  proteins  from  the  insoluble  fibrin. 
If  the  action  be  allowed  to  proceed  for  some  hours,  a  whole  series  of 
products  of  hydrolysis  are  found  in  the  mixture.  On  neutralising 
the  fluid,  a  precipitate  may  be  thrown  down  consisting  chiefly  of 
acid  albumen.  The  greater  proportion  of  the  protein  remains  in 
solution.  This  remainder  may  be  purified  from  any  unaltered  coagu- 
lable protein  by  boiling  in  slightly  acid  solution  and  filtering.  The 
filtrate  contains  a  mixture  of  bodies  belonging  to  the  class  of  hydrated 
proteins,  viz.  proteoses  and  peptones. 

By  means  of  fractional  precipitation  with  ammonium  sulphate 
or  zinc  sulphate,  these  mixtures  can  be  subdivided  into  various 
substances,  although  in  no  case  can  we  be  certain  that  we  are  dealing 
with  chemical  individuals.  The  Table  on  p.  770  represents  the  chief 
bodies  obtained  by  Pick  by  this  method  from  '  Witte's  peptone,' 
a  commercial  preparation  containing  proteoses  and  peptones. 

The  follo^^^ng  careful  analysis  of  the  constituents  of  protoalbumose 
and  heteroalbumose  (or  protoproteose  and  heteroproteose)  respectively 
shows  that  the  different  proteoses  really  correspond  to  different  group- 
ings of  the  amino-acids  making  up  the  original  protein  molecule  : 


Results  of  the  Complete  Hydrolysis 

OF  Heteko-  and 

Protoalbcmose 

Heteroalbumose 

Protoalbumose 

Glutaniinic  acid  ..... 

9ol 

0-63 

Leucine 

3  05 

5-79 

Isoleucine   . 

2-96 

1-62 

Valine 

3.54 

0-76 

Alanine 

3-39 

2-50 

Valine-alanine  mixture 

1-86 

000 

Proline 

4-27 

4-96 

Phenylalanine 

2-45 

4-35 

Aspartic  acid 

4-73 

2-98 

Glycocoll    . 

015 

1-44 

TjTosine     . 

3-48 

4-58 

Argininc 

7-30 

7-72 

Histidine    . 

3-90 

2-77 

Lysine 

8-90 

8-40 

Cystine 

1-36 

0-68 

Amwonia   . 

1-28 

0-92 

T\e  results  obtained  by  Pick  by  hydrolysis  of  these  different  bodies 
i^show  <^hat  in  the  breakdown  of  protein  produced  by  gastric  juice  there 

49 


770 


PHYSIOLOGY 


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DIGESTION  IN  THE  STOMACH  771 

is  really  a  division  of  the  complex  molecule  into  smaller  molecules, 
which  are  c[uahtatively  different.  Thus  of  the  fractions  which  he 
obtained,  some  contain  the  greater  part  of  the  sulphur  originally 
present  in  the  protein  molecule,  another  contains  the  greater  part 
of  the  carbohydrate  gTOup,  while  others  are  free  altogether  from 
the  tryptophane  group  which  is  responsible  for  Hopkins'  reaction 
obtainable  in  the  original  protein. 

Proceeding  from  primary  through  secondary  albumoses  to  peptones, 
there  is  probably  a  continuous  diminution  in  the  size  of  the  molecule. 
During  the  time  which  gastric  juice  has  to  exert  its  influence,  a 
maximum,  say,  of  twelve  hours,  the  breakdown  of  proteins  never 
passes  beyond  the  albumose  and  peptone  stage,  and  it  is  in  this 
form  that  the  proteins  of  the  food  pass  on  through  the  pyloric  orifice 
into  the  small  intestine. 


ACTION  ON  THE  CONNECTIVE  TISSUES   AND  OTHER 
FOOD-STUFFS   ALLIED  TO  PROTEINS 

Collagen.  The  connective  tissues  are  made  up  chiefly  of  white 
fibres,  more  or  less  modified,  which  consist  of  collagen.  This  substance 
forms  the  main  basis  of  areolar  tissue,  of  white  fibrous  tissue,  and  of 
bone.  On  prolonged  boiling,  it  is  converted  into  gelatin.  The  gastric 
juice  dissolves  collagen,  converting  it,  probably  through  the  stage 
of  gelatin,  into  gelatoses  and  gelatin  peptones,  bearing  the  same 
relation  to  the  original  substance  as  is  borne  by  the  proteoses  and 
peptones  to  the  proteins.  On  account  of  this  action,  adipose  tissue 
(which  consists  of  protoplasmic  cells  distended  with  fat,  and  bound 
together  by  connective  tissue)  is  "broken  up  into  its  constituent 
cells.  The  protoplasmic  pellicle  is  dissolved,  and  the  fat  floats  freely 
in  the  gastric  juice. 

Elastin,  which  also  occurs  in  varying  amounts  as  the  chief 
constituent  of  the  elastic  fibres  of  connective  tissues,  is  slowly  acted 
upon  by  gastric  juice.  Under  the  conditions  of  natural  digestion, 
however,  it  may  be  regarded  as  indigestible. 

Mucin,  which  forms  a  considerable  proportion  of  the  ground 
substance  of  connective  tissues,  is  converted  by  gastric  juice  into 
peptone-like  substances,  and  into  reducing  bodies  probably  allied 
to  glycosamine. 

The  NUCLEO-PROTEINS,  the  chief  constituents  of  cells,  and  therefore 
ingested  in  large  amounts  with  food-stuffs  such  as  sweetbreads,  are 
first  dissolved  by  the  acid  of  the  gastric  juice,  and  are  then  broken 
up  into  two  moieties.  The  protein  half  is  converted  into  proteoses 
and  peptones,  while  the  nuclein  moiety  is  precipitated  in  an  insoluble 
form. 


772  PHYSIOLOGY 

On  PHOSPHO-PROTEiNS  gastric  juice  acts  in  a  somewhat  similar 
manner.  The  protein  of  milk,  caseinogen,  undergoes  special  changes 
in  the  stomach.  The  first  effect  of  gastric  juice,  even  in  neutral 
medium,  is  to  convert  the  caseinogen  into  an  insoluble  casein.  This 
action  is  generally  ascribed  to  the  presence  of  a  distinct  ferment 
of  the  gastric  juice,  named  rennin,  or  rennet  jerment.  But,  according 
to  some  authorities,  it  is  due  directly  to  the  pepsin,  i.e.  rennin  and 
pepsin  are  identical.  For  the  conversion  of  caseinogen  into  the  sohd  clot 
of  casein  the  presence  of  lime  salts  is  necessary.  The  addition  of  rennet 
to  an  oxalated  milk  apparently  produces  no  effect,  but  clotting  ensues 
if  a  soluble  hme  salt,  such  as  calcium  chloride,  is  then  added  to  the 
mixture.  Under  the  action  of  the  acid  gastric  juice  the  sohd  clot 
of  casein  is  dissolved,  but  a  precipitate  is  left  containing  a  small 
proportion  of  the  original  phosphorus  of  the  caseinogen.  This  pre- 
cipitate is  sometimes  spoken  of  as  para-nuclein,  or  'pseudo-niiclein. 
It  does  not  yield  the  typical  purin  bases  on  hydrolysis  with  acids, 
but  contains  phosphoric  acid  in  organic  combination.  By  prolonged 
digestion  with  strong  gastric  juice  it  is  possible  to  dissolve  "the  whole 
of  this  precipitate.  It  is  therefore  thought  that  in  the  clotting  of 
milk  the  caseinogen  under  the  action  of  the  rennet  first  undergoes 
a  conversion  into  a  soluble  casein,  or  perhaps  a  spHtting  into  a 
soluble  casein  and  some  other  globuhn-hke  body.  The  soluble 
casein  then,  under  the  influence  of  the  lime  salts,  forms  an  insoluble 
casein  which  is  precipitated,  and  causes  the  sohdification  of  the  milk. 
In  the  absence  of  lime  salts,  the  conversion  or  splitting  of  caseino- 
gen takes  place,  but  the  second  stage  of  the  process  cannot  occur 
until  the  lime  salts  are  added. 


THE  EFFECT  OF  GASTRIC  JUICE  ON  CARBOHYDRATES 
On  account  of  the  fact  that  cane  sugar  undergoes  inversion  into 
equal  molecules  of  glucose  and  fructose  in  the  stomach,  it  has  been 
sometimes  thought  that  gastric  juice  contains  a  ferment  invertase. 
It  seems,  however,  that  the  inversion  which  takes  place  in  the  stomach 
can  be  completely  accounted  for  by  the  action  of  hydrochloric  acid 
present,  and  that  there  is  no  need  to  assume  the  presence  of  a  special 
ferment. 

In  the  same  way  inuhn,  the  variety  of  starch  which  gives  rise 
to  the  laevorotatory  sugar  fructose  on  hydrolysis,  and  is  found 
in  dahlia  tubers  and  certain  other  reserve  structures  of  plants,  is 
converted  b}^  the  acid  of  gastric  juice  into  fructose.  The  inuhn  is 
therefore  completely  utilised  in  the  ahmentary  canal  of  animals, 
although  there  is  no  definite  ferment  inulase  provided  for  its  hydrolysis. 


DIGESTION  IN  THE  STOMACH 


773 


THE  EFFECT  OF  GASTRIC  JUICE  ON  FATS 
The  cliief  action  of  this  juice  on  i'ats  is  the  solution  of  their  con- 
nective-tissue framework  and  protoplasmic  envelopes,  so  as  to  set 
the  fat  free  in  the  stomach  contents.  After  a  fatty  meal  it  is  found 
moreover  that  a  considerable  proportion  of  the  fat  in  the  stomach 
has  undergone  hydrolysis  and  conversion  into  free  fatty  acid.  In 
this  hydrolysis  two  factors  are  involved,  viz.  (1)  the  action  of  the 
warm  dilute  hydrochloric  acid  ;  (2)  the  action  of  a  special  fat- 
splitting  ferment  or  lipase,  which  is  secreted  by  the  walls  of  the 
stomach,  and  acts  especially  at  the  beginning  of  gastric  digestion 
before  the  contents  have  attained  a  hidi  dejrree  of  aciditv.     The 


Fig.  334.  Diagram  to  show  Pawlow's  method  of  making  a  cul-de-sac  of  the 
cardiac  end  of  the  stomach,  \nth  vascular  and  nerve  supply  intact. 
In  A  the  line  of  the  incision  into  the  stomach  wall  is  sho\Mi.  B  represents 
the  operation  as  completed.  In  A  :  0,  oesophagus  ;  B.v,  L.v,  right  and  left 
vagus  nerves  ;  P,  pylorus  ;  C,  cardiac  portion  of  stomach  ;  A,  B,  line  of 
incision.  In  B  :  V,  main  portion  of  stomach  ;  S,  cardiac  cul-de-sac  ;  A, 
abdominal  wall ;  e,  e,  mucous  membrane  reflected  to  form  diaphragm  between 
the  two  cavities. 


action  of  this  ferment  is  only  marked  if  the  fat  be  present  in  a  finely 
divided  form,  e.g.  as  yolk  of  egg.  The  chief  digestion  of  fat  takes 
place  in  the  next  segment  of  the  alimentary  canal,  namely,  in  the 
duodenum. 

THE  SECRETION  OF  GASTRIC  JUICE 
Pawlow  has  shown  that  if  an  animal  provided  with  gastric  and 
oesophageal  fistulae  be  given  food,  when  hungry,  it  will  eat  with 
avidity,  and  since  the  food  cannot  reach  tlie  stomacli  and  so  satisfy 
its  hunger,  it  will  continue  to  eat  for  two  or  three  hours.  Five 
minutes  after  the  beginning  of  this  sham  feeding,  gastric  juice  begins 
to  drop  from  the  fistulous  opening  ;  and  in  this  way  large  (piantities 
of  juice,  free  from  any  admixture  with  other  substances,  can  be  easily 
obtained.    By  this  means  we  obtain  a  secretion  of  gastric  juice,  which 


774 


PHYSIOLOGY 


is  excited  by  the  presence  of  food  in  the  mouth.  This  method  does 
not,  however,  enable  us  to  determine  whether  the  character  of  the 
juice  will  be  altered  in  any  way  by  the  changes  which  the  food  under- 
goes in  the  stomach  itself.  In  order  to  form  an  idea  of  the  normal 
course  of  secretion  of  gastric  juice,  when  food  is  taken  into  the  stomach 
in  the  ordinary  way,  Pawlow  has  devised  another  procedure.  A 
small  diverticulum  representing  about  one-tenth  of  the  whole  stomach 
is  made  at  the  cardiac  or  pyloric  end,  in  direct  muscular  and  nervous 
continuity  with  the  rest  of  the  stomach,  but  shut  off  from  the  main 
part  of  the  viscus  by  a  diaphragm  of  mucous  membrane.  The  method 
in  which  this  operation  is  carried  out  will  be  evident  by  reference 
to  the  diagram  (Fig.  334).  In  a  dog  treated  in  this  way  it  is  found 
that  the  amount  of  juice  secreted  by  the  small  stomach  always  bears 
the  same  ratio  to  the  amount  secreted  by  the  large  stomach,  while 
the  digestive  power  of  the  juice  obtained  from  the  small  stomach  is 
equal  to  that  obtained  from  the  large.  This  is  shown  in  the  following 
Table :  * 

Secretion  from  Gastric  Fistul.?-:  after  Shajm  Meal 


Hours 

Small  stomach 

Large  stomach 

Quantity 

strength  f 

Quantity 

Strength 

1 

2 
3 

7-6  C.C. 
4-7  c.c. 
M  c.c. 

5-88  mm. 
5-75  mm. 
5-5    mm. 

68-25  c.c. 
41-5    c.c. 
14-0    c.c. 

5-5    mm. 
5-5    mm. 
5-38  mm. 

Total 

13-4  c.c. 

— 

123-75  c.c. 

— 

In  this  case  a  fistulous  opening  had  been  established  into  the 
large  stomach,  so  that  the  juice  could  be  obtained  simultaneously 
from  both  sections  of  this  organ.  Secretion  was  excited  by  a  sham 
meal,  in  which  the  food  taken  by  the  animal  dropped  out  of  an  opening 
in  the  neck,  and  was  not  allowed  to  reach  the  stomach.  It  will  be 
seen  that  the  secretions  in  the  two  sections  of  the  stomach  run  parallel 
to  one  another,  while  there  is  an  almost  exact  equivalence  between 
the  strengths  of  the  juices  obtained  from  each  section.  We  may 
therefore  regard  the  secretion  obtained  from  the  small  stomach  as 
a  sample  of  that  produced  by  the  large,  and  from  the  changes  in 
this  small  stomach  judge  of  the  effects  occurring  in  the  whole  organ. 

*  Pawlow,  "  The  Work  of  the  Digestive  Glands  "  (translated  by  W.  H. 
Thompson,  M.D.),  p.  80. 

*f  The  strength  of  the  juice  was  determined  by  measuring  the  number  of 
millimetres  of  coagulated  egg-white  (in  Mett's  tubes)  which  were  digested  in 
eight   hours. 


DIGESTION  IX  THE  STOMACH 


775 


By  this  method  it  is  possible  to  study  the  effects  of  a  normal  meal 
in  which  the  food  is  swallowed,  or  of  a  sham  meal  in  which  the  food 
is  merely  masticated  in  the  mouth,  or  of  a  meal  in  which  the  food 
is  directly  introduced  into  an  opening  into  the  large  stomach. 

The  method  which  we  must  adopt  for  the  collection  of  gastric 
juice  shows  that  we  have  to  do,  in  the  first  place,  with  a  reflex 
nervous  mechanism,  since  an  active  secretion  is  excited  by  the  pres- 
ence of  food  in  the  mouth  and  by  its  mastication.  Moreover  a  secre- 
tion, which  is  at  least  as  vigorous  as  that  produced  by  a  sham  meal, 
can  be  evoked  by  merely  arousing  in  the  dog  the  idea  of  a  meal. 
If  the  animal  be  hungry,  it  is  sufficient  to  show  it  the  food  to  produce 
a  secretion.  In  the  experiment  from  which  the  following  Table  is 
taken,  the  dog  was  continually  excited  by  showing  it  meat  during 
a  peiiod  of  an  hour  and  a  half.  At  the  end  of  this  time  the  animal, 
which  had  an  oesophageal  fistula,  was  given  a  sham  meal.  It  will  be 
observed  that  the  psychical  secretion  obtained  during  the  first  period 
of  the  experiment  was  rather  greater  than  the  secretion  produced 
by  the  introduction  of  food  into  the  mouth. 


PsYCHicAi,  Seceetion  OF  Gastric  Juice  (Pawxow) 
Time  Quantity 


8  minutes 

10  c.c. 

4 

10  „ 

4 

10  „ 

10 

10  ., 

10 

10  « 

8 

10  „ 

8         „ 

10  „ 

19 

10  ., 

9 

3  „ 

Sham  Feedixq 

Time 

Quantity 

17  minutes 

. 

10  c.c. 

9 

. 

10  ., 

8         ,, 

, 

, 

,         , 

10  „ 

The  afferent  channels  for  this  reflex  may  be  therefore  either  the 
afferent  nerves  from  the  mouth,  or,  when  the  idea  of  food  is  involved, 
any  of  the  nerves  of  special  sense,  such  as  sight,  smell,  or  hearinu, 
through  which  these  ideas  are  called  forth.  The  efferent  channels 
can  only  be  one  of  two  nerves,  viz.  the  vagus  and  the  sympathetic, 
since  these  are  the  only  two  which  are  distributed  to  the  stomach. 
That  it  is  the  former  of  these  nerves  which  is  involved  is  shown  by 
the  fact,  recorded  by  Pawlow,  that  psychical  secretion,  as  well  as 
the  results  of  a  sham  meal,  is  entirely  abolished  by  division  of  both 
vagi.     On  this  account  division  of  both  vagi  may  give  rise  to  entire 


776  PHYSIOLOGY 

absence  of  gastric  digestion,  and  death  of  the  animal  may  ensue 
from  inanition,  or  from  poisoning  by  the  products  of  decomposi- 
tion of  food  in  the  stomach,  even  when  care  has  been  taken  to 
avoid  injury  to  thet  puhnonary  and  tracheal  branches  of  these 
nerves. 

The  converse  experiment  of  exciting  secretion  by  direct  stimula- 
tion of  the  vagus  presents  greater  difficulties.  Stimulation  of  the 
vagus  in  the  neck  causes  stoppage  of  the  heart,  and  consequent 
anaemia  of  the  mucous  membrane  of  the  stomach.  Moreover,  the 
stomach  seems  to  be  much  more  susceptible  than  the  sahvary  glands 
to  the  action  of  poisons,  such  as  anaesthetics.  Its  activity  is  also 
easily  affected  by  inhibitory  impulses  arising  in  the  central  nervous 
system  as  the  result  of  either  painful  impressions  or  emotional  states 
of  the  animal.  In  order  to  avoid  these  disturbing  factors  Pawlow 
proceeded  as  follows  :  An  animal  w^ith  fistulaB  of  oesophagus  and 
stomach  had  one  vagus  nerve  divided.  A  thread  was  attached 
to  the  peripheral  end  of  the  cut  vagus  and  allowed  to  hang  out  through 
the  wound.  Fom-  days  after  the  operation  the  vagus  was  drawn 
out  of  the  wound  by  carefully  pulling  on  the  thread,  so  as  not  to 
hurt  or  frighten  the  animal  in  any  way,  and  its  peripheral  end  stimu- 
lated by  means  of  induction  shocks.  No  effect  was  produced  on  the 
heart,  owing  to  the  degeneration  of  the  cardio-inhibitory  fibres, 
which  is  well  known  to  occur  within  this  period  after  section.  Five 
minutes  after  the  commencement  of  the  stimulation  the  first  drop 
of  gastric  juice  appeared  from  the  gastric  cannula,  and  a  steady 
secretion  of  juice  w^as  obtained  with  continuation  of  the  stimulation. 
This  experiment  furnishes  the  decisive  and  final  evidence  that  the 
secretory  nerves  to  the  stomach  run  in  the  two  vagi.  There  is  one 
marked  difference,  however,  between  the  action  of  these  nerves 
and  the  action  of  the  chorda  tympani  nerve  on  the  submaxillary  gland, 
namely,  the  great  length  of  the  latent  period  before  gastric  secretion 
occurs.  The  length  of  this  latent  period  has  not  yet  been  satisfactorily 
explained.  It  cannot  be  due  to  delay  occurring  between  the  vagus 
fibres  and  the  local  nervous  mechanism  in  the  stomach.  It  may  be 
that  the  chemical  changes  finally  resulting  in  secretion  require  a 
longer  period  for  their  accomplishment  than  is  the  case  in  the  salivary 
gland.  Physiologically  there  is,  indeed,  no  special  need  for  a  rapid 
secretion  of  gastric  juice,  whereas  in  the  mouth  it  is  essential  that 
the  introduction  of  food  should  be  immediately  followed  by  the 
production  of  saliva,  for  the  tasting  and  testing  of  the  food  and  for 
its  subsequent  mastication  or  rejection. 

These  experiments  show  conclusively  that  an  important — probably 
the  most  important — part  of  the  gastric  secretion  is  determined 
by  a  nervous  mechanism.     This  nervous  secretion  does  not,  however. 


DIGESTION  IN  THE  STOMACH  777 

account  for  the  whole  of  the  gastric  juice  obtained  as  the  result  of 
a  meal.  If  an  aiiiinal  provided  with  two  <iastric  fistula),  one  into 
a  diverticulum  and  the  other  into  the  main  stomach,  has  both  its 
vagi  divided,  it  is  found  that  the  introduction  of  meat  into  the  large 
stomach  is  followed,  after  a  period  of  twenty  to  forty-five  minutes, 
by  the  appearance  of  a  secretion  of  gastric  juice  from  the  small 
stomach.  Moreover,  when  an  animal  is  given  a  normal  meal  and 
is  allowed  to  swallow  the  food  after  mastication,  the  total  amount  of 
gastric  juice  obtained  is  greater  than  that  produced  by  the  sham 
feeding  alone,  and  the  flow  is  of  longer  dm-ation.  In  fact,  we  may 
say  that  the  gastric  juice  secreted  in  response  to  a  normal  meal 
consists  of  two  parts,  viz.  :  (1)  a  large  amount,  the  secretion  of  which 
begins  within  five  minutes  of  the  taking  of  the  food  and  is  determined 
by  the  reflex  nervous  mechanism  described  above  ;  and  (2)  a  smaller 
portion,  the  secretion  of  which  is  excited  by  the  presence  of  the 
food  in  the  stomach.  This  combined  character  of  the  gastric  juice 
produced  by  a  normal  meal  is  shown  in  the  following  Table  (Pawlow)  : 


Secretion  of  Gastric  Juice"' 

Nonmil  meal. 

200  grni.  meat  into 

stomach 

150  grm.  meat  into 
stomach 

Sliam  meal 

Sum  of  two 
last  ex- 
periments 

Hours 

(Quantity       Strength 
c.c.        1        mm. 

Quantity 
c.c. 

Strength 
mm. 

Quantity 
c.c. 

Strength 
mm. 

Quantity 
c.c. 

1 

12-4 

5-43 

5-0 

2-5 

7-7 

6-4 

12-7 

2 

13-5 

3-63 

7-8 

2-75 

4-5 

5-3 

12-3 

3 

7-5 

3-5 

i       6-4 

3-75 

0-6 

5-75 

7-0 

4 

4-2 

312 

5-0 

3-75 

0 

0 

50 

In  the  first  column  is  given  the  result  of  a  normal  meal  on  the 


secretion   from    the    gastric   diverticulmn 


In  the  second  column 
are  given  the  amount  and  digestive  power  of  the  juice  which  is  excited 
by  the  direct  introduction  of  150  grm.  of  meat  into  the  large  stomach 
of  the  animal,  care  being  taken  not  to  excite  in  any  way  the  nervous 
reflex  mechanism.  In  the  third  column  are  given  the  amount  and 
digestive  power-  of  the  juice  which  is  evoked  by  a  sham  meal  of 
200  grm.  of  meat.  In  the  fourth  column  is  given  the  sum  of  the  last 
two  experiments.  It  will  be  seen  that  the  total  eft'ect  of  the  sham 
meal  pluti  the  direct  introduction  of  meat  into  the  stomach  is  almost 
identical  with  the  secretion  obtained  when  the  food  is  taken  in  a 
noiinal  wa\-  and  allowed  to  pass  through  the  oesophagus  into  the 
stomaili. 

The  second  phase  of  the  gastric  secretion  cannot  be  ascribed  to 


778  PHYSIOLOGY 

the   intervention   of   the  reflex   vagal  mechanism.     Since  it  occm"s 
after  cutting  off  the  stomach  from  its  connections  with  the  central 
nervous  system,  it  must  have  its  causation  in  the  gastric  walls  them- 
selves.    That  it  cannot  be  due  to  mechanical  stimulation  is  shown 
by  the  fact,  previously  mentioned,  that   it  is  impossible  by  local 
stimulation  of  the  mucous  membrane,  by  rubbing,  or  introduction  of 
sand,  or  any  other  method,  to  evoke  a  secretion.      Moreover  it  is 
not  produced  by  all  sorts  of  food.     The  introduction  of  white  of 
egg,  of  starch,  or  of  bread  into  the  stomach  causes  no  secretion. 
On  the  other  hand,  if  bread  be  mixed  with  gastric  juice  and  allowed 
to  digest  for  some  time,  the  introduction  of  the  semi-digested  mixture 
into  the  stomach  evokes  a  secretion.     We  have  already  seen  that 
meat  produces  a  secretion ;    still  more  potent  than  meat,  however, 
is  a  decoction  of  meat,  or  bouillon,  or  Liebig's  extract  of  meat,  or 
certain    preparations    of    peptone.     Pure    albumoses    and    peptones 
have  no  effect,  so  that  the  exciting  mechanism  must  be  some  chemical 
substances  present  in  meat,  and  produced  in  various  other  foods 
under  the  action  of  the  first  gastric  juice  secreted  in  response  to 
nervous   stimuli.     Popielski   has   shown   that   this   secretion   occurs 
after  complete  severance  of  the  stomach  from  the  central  nervous 
system,   as  well  as   after  destruction  of    the  sympathetic   nervous 
plexuses  of  the  abdomen.     Since  the  injection  of  bouillon  directly 
into  the  circulation  has  no  effect,  this  author  concludes  that  the 
second  phase  of  secretion  is  determined  by  the  stimulation  of  the 
local  nerve  plexus,  and  that  we  havie  here,  in  short,  a  peripheral 
reflex  action,  the  centres  of  which  are  situated  in  the  walls  of  the 
stomach  itself.     There  is,  however,  one  possible  explanation  for  this 
second  phase  of  secretion  which  was  not  sufiiciently  considered  either 
by  Pawlow  or  by  Popielski.     Although  the  peptogenic  substances, 
those  substances  which  evoke  gastric  secretion  on  introduction  into 
the  stomach,  have  no  effect  on  the  gastric  glands  when  injected 
directly  into  the  blood  stream,  it  is  possible  that  they  may  have 
an  influence  on  the  cells  which  line  the  cavity  of  the  stomach,  and 
that  they  may  produce,  in  these  cells,  some  other  substance  which 
is  absorbed    into    the    blood,    and    acts    as   a   specific    excitant  of 
the  gastric  glands.    A    process    of   this    nature  is  known  to  occur 
in  the  next  segment  of  the  ahmentary  canal,  viz.  the  duodenum, 
where  it  determines  the  secretion  of  the  pancreatic  juice  and  the 
bile. 

Edkins  has  carried  out  a  series  of  experiments  to  determine 
whether  such  a  chemical  mechanism  may  not  also  account  for  the 
secretion  of  gastric  juice,  which  is  excited  by  the  introduction  of 
substances  into  the  stomach.  Edkins'  experiments  were  carried 
out  in  the  following  way :     The  animal,  dog  or  cat,  having  been 


DIGESTION  IN  THE  STOMACH  779 

anaesthetised,  the  abdominal  cavity  was  opened,  and  a  ligature  passed 
round  the  lower  end  of^the  oesophagus  so  as  to  occlude  the  cardiac 
orifice  and  effectually  crush  the  two  vagus  nerves.  A  glass  tube  was 
then  introduced  through  an  opening  in  the  abdomen  into  the  pyloric 
part  of  the  stomach,  and  fixed  in  this  position  by  a  ligature  tied 
tightly  round  the  pylorus.  The  glass  tube  was  connected  by  means 
of  a  rubber  tube  with  a  reservoir  containing  normal  salt  solution 
at  the  temperatm-e  of  the  body.  By  means  of  this  reservoir,  a  certain 
amount  of  fluid  was  introduced  into  the  stomach  and  kept  there  at 
a  constant  pressure  ;  the  quantity  of  fluid  introduced  varied  from 
30  to  50  c.c.  It  has  been  shown  by  Edkins,  as  well  as  by  von  Mering, 
that  no  absorption  of  water  or  saline  fluid  occurs  in  the  stomach. 
It  is  therefore  possible  to  recover  the  whole  of  the  fluid  an  hour 
after  it  has  been  introduced,  by  simply  lowering  the  reservoir  below 
the  level  of  the  animal's  body.  If  secretion  of  gastric  juice  has 
occurred  into  the  cavity  of  the  stomach,  the  fluid  will  be  increased 
in  amount,  and  will  contain  hydrochloric  acid  as  well  as  pepsin. 
In  a  series  of  control  observations  Edkins  showed  that  the  mere 
introduction  of  this  fluid  into  the  stomach  caused  no  secretion  of 
gastric  juice,  the  fluid  removed  at  the  end  of  an  hour  having  the 
same  bulk  and  the  same  neutral  reaction  as  the  fluid  which  had  been 
injected.  Edkins  then  tried  the  influence  of  injecting  substances 
into  the  blood  stream.  The  injection  of  peptone,  of  acid,  of  broth, 
or  of  dextrin  into  the  blood  stream  produced  no  secretion  of  gastric 
juice.  If,  however,  in  the  course  of  the  hour  during  which  the  fluid 
was  allowed  to  remain  in  the  stomach,  a  decoction  made  by  boiling 
pyloric  mucous  membrane  with  acid,  or  with  water,  or  with  peptone 
was  introduced  in  small  quantities  every  ten  minutes  into  the  jugular 
vein,  the  fluid  removed  at  the  end  of  the  hour  was  found  to  be  dis- 
tinctly acid  in  its  reaction  and  to  possess  proteolytic  properties. 
The  injection  of  these  substances  had  therefore  caused  the  secretion 
of  a  certain  amount  of  gastric  juice  containing  both  hydrochloric 
acid  and  pepsin.  In  order  to  produce  this  positive  effect,  it  was 
necessary  to  employ  pyloric  mucous  membrane,  extracts  made  by 
infusing  or  boiling  cardiac  mucous  membrane  with  any  of  these 
substances  being  without  effect.  Edkins  concludes  therefore  that 
the  secondary  secretion  of  gastric  juice  is  determined,  not,  as  Paw  low 
and  Popielski  imagined,  by  a  local  stimulation  of  the  reflex  nervous 
apparatus  in  the  gastric  wall,  but  by  a  chemical  mechanism.  The 
first  products  of  digestion  act  on  the  pyloric  mucous  membrane,  and 
produce  in  this  membrane  a  substance  which  is  absorbed  into  the 
blood  stream,  and  carried  to  all  the  glands  of  the  stomach,  where  it 
acts  as  a  specific  excitant  of  their  secretory  activity.  This  substance 
may  be  called  the  gastric  secretin  or  gastric  hormone.     It  is  noteworthy 


780  PHYSIOLOGY 

that  it  is  produced  in  that  portion  of  the  stomach  where  the  process 
of  absorption  is  most  pronomiced. 

The  normal  gastric  secretion  is  therefore  due  to  the  co-operation 
of  two  factors.  The  first  and  most  important  is  the  nervous  secretion, 
determined  through  the  yagiis  nerves  by  stimulation  of  the  mucous 
membrane  of  the  mouth,  or  by  the  arousing  of  appetite  in  the  higher 
parts  of  the  brain.  The  second  factor,  which  provides  for  the  con- 
tinued secretion  of  gastric  juice  long  after  the  mental  effects  of  a 
meal  have  disappeared,  is  chemical,  and  depends  on  the  production 
in  the  pyloric  mucous  membrane  of  a  specific  substance  or  hormone, 
which  acts  as  a  chemical  messenger  to  all  parts  of  the  stomach,  being 
absorbed  into  the  blood  and  thence  exciting  the  activity  of  the  various 
secreting  cells  in  the  gastric  glands.  It  is  still  a  moot  point  whether  this 
gastric  hormone  is  formed  only  in  the  pyloric  mucous  membrane,  or 
whether  it  may  not  be  also  produced  in  the  lower  sections  of  the  gut. 
Popielski  has  stated  that  the  introduction  of  bouillon  into  the  small 
intestine  excites  a  secretion  of  gastric  juice  in  animals,  even  after  extir- 
pation of  the  abdominal  sympathetic  plexuses  and  division  of  both  vagi. 
On  the  other  hand,  introduction  of  the  same  substance  into  the  large 
intestine  has  no  influence  on  gastric  secretion.  Popielski  ascribes 
this  secretion  again  to  a  local  reflex  ;  but  it  is  more  probable  that 
the  mechanism  in  this  case  is  the  same  as  that  involved  in  the  secretion 
which  is  excited  by  the  presence  of  semi- digested  food  in  the  stomach 
itseK. 

Pawlow  has  shown  that  the  secorid  phase  of  the  gastric  secretion 
is  largely  influenced  by  the  character  of  the  contents  of  the  stomach. 
Thus  the  ingestion  of  large  quantities  of  oil  diminishes  considerably 
the  amount  of  gastric  juice  secreted,  and  Pawlow  has  suggested 
the  administration  of  oil  or  oily  foods  as  a  possible  remedy  in  cases 
where  the  production  of  gastric  juice,  and  especially  of  hydrochloric 
acid,  is  in  excess.  It  has  long  been  imagined  that  the  secretion  of 
gastric  juice  was  stimulated  by  the  taking  of  alkahes.  This  idea 
has  been  shown  by  Pawlow  to  be  erroneous.  Whereas  the  formation 
of  gastric  juice  is  increased  by  the  administration  of  acids,  especially 
after  a  meal,  it  is  largely  diminished  by  the  administration  of  alkalies 
such  as  sodium  bicarbonate.  In  fact,  sodium  bicarbonate  diminishes 
the  activity  of  the  digestive  glands  throughout  the  alimentary  tract, 
and  can  be  used  as  a  means  of  diminishing  the  secretion  of  gastric 
juice  as  well  as  of  pancreatic  juice. 

A  further  important  question  has  been  propounded  by  Pawlow, 
namely,  whether  there  is  any  alteration  in  the  constitution  and 
amount  of  gastric  juice  with  variations  in  the  character  of  the  food. 
So  far  as  concerns  the  first  phase  of  secretion,  the  psychical  or  '  appetite' 
juice,  this  observer  has  shown  that,  whatever  the  previous  diet  of 


DIGESTION  IN  THE  STOMACH 


781 


the  animal,  the  juice  always  has  the  same  characters,  the  same 
digestive  power,  and  the  same  percentage  of  hydrochloric  acid. 
He  finds,  however,  that  in  the  case  of  the  second,  or  what  we  may  call 
'  chemical '  secretion,  i.e.  that  produced  by  local  changes  in  the 
stomach,  there  is  considerable  variation  in  the  nature  of  the  juice. 
In  the  following  Table  are  shown  the  relative  effects  of  meat  and 
of  milk,  when  introduced  into  the  large  stomach,  in  determining 
a  flow  of  juice  from  the  small  stomach  of  an  animal  with  a 
Pawlow  fistula.  Whereas  the  secretion  of  juice  is  greatest  in  amount 
with  the  meat,  the  digestive  power  of  the  juice  is  greatest  with  the 


Hours 

Gastric  secretion  aftor 

100  ftrm.  moat. 

Two  experiments 

Hours 

Gastric  secretion  after 

600  c.c.  mill<. 

Iwo  experiments 

Quantity  of  juice 

Quantity  of  juice 

1 

11-2 

12-6 

1 

8-75 

8-2.'; 

2 

8-2 

8-0 

2 

7-5 

6-0 

3 

4-0 

2-2 

3 

22-5 

230 

4 

1-9 

M 

4 

9-0 

6-25 

5 

0*1          '        a  drop 

5 

2-0 

lo 

Total 

25-4         i         23-9 

Total 

49-75 

450 

bread,  and  Pawlow  regards  these  differences  in  the  juice  as  deter- 
mined by  the  variations  in  the  stimulus  applied  to  the  gastric  mucous 
membrane.  It'^is  doubtful,  however,  whether  these  results  justify  us 
in  ascribing  a  number  of  specific  sensibilities  to  the  gastric  mucous 
membrane.  We  have  seen  that  the  psychical  juice  depends  merely 
on  appetite,  and  therefore  will  be  greater  in  amount  the  more  welcome 
the  food  is  to  the  animal.  On  the  other  hand,  the  juice  secreted  in 
the  second  phase  must  vary  according  to  the  quantity  of  gastric 
hormone  produced  in  the  pyloric  mucous  membrane,  and  there- 
fore with  the  nature  and  amount  of  the  substances  produced  in  the 
preliminary  digestion  of  the  gastric  contents  by  means  of  the  psychic 
juice.  The  amount  of  juice  may  vary  also  with  the  salts  contained 
in  the  food,  according  to  their  alkaline  or  acid  character,  and  the 
percentage  of  pepsin  in  the  juice  may  vary  with  the  intensity  of 
stimulus  as  well  as  with  the  quantity  of  fluid  available  for  the  forma- 
tion of  the  gastric  juice.  These  factors  will  co-operate  in  determining 
the  characters  of  the  whole  juice  secreted  after  any  given  meal,  and 
it  seems  possible  to  explain  the  variations,  observed  on  such  different 
diets  as  meat  and  bread,  without  having  recourse  to  the  difficult 
assumption  of  a  specific  sensibility  of  the  gastric  mucous  membrane 
to  such  inert  substances  as  dextrin  or  egg  albumin. 


SECTION  IV 
THE  MOVEMENTS  OF  THE  STOMACH 


These  can  be  best  studied  by  Cannon's  method — that  is,  by  direct 
observation  of  the  movements  in  a  living  unansesthetised  anrmal 
by  means  of  the  Rontgen  rays.  In  order 
to  make  the  shape  of  the  stomach  visible, 
the  food^ — ^bread  and  milk — is  mixed  with  a 
quantity  of  bismuth  subnitrate  or  bismuth 
oxychloride  (Hertz).  The  presence  of  this 
salt  does  not  interfere  with  the  processes  of 
digestion,  but  renders  the  gastric  contents 
opaque  to  the  Rontgen  rays.  On  examin- 
ing by  this  means  the  stomach  of  a  cat 
which  has  just  taken  a  meal,  the  whole  of 
the  food  is  seen  to  be  lying  in  the  fundus. 
It  is  marked  off  by  a  strong  constriction, 
the  '  transverse  band,'  from  the  pyloric 
portion.  In  about  twenty  to  thirty  minutes 
faint  waves  "of  contraction  begin  a  little  to 
the  cardiac  side  of  the  transverse  band  and 
travel  slowly  towards  the  pylorus.  These 
waves  succeed  one  another  so  that  the 
pyloric  part  of  the  stomach  may  present 
a  series  of  constrictions.  Their  effect  is  to 
force  towards  the  pylorus  the  food  which 
has  been  digested  by  the  gastric  juice  and 
detached  from  the  surface  of  the  mass  in 
the  fundus.  The  pylorus  remaining  closed, 
cannot   escape,  and    therefore  is 


Shadow  sketches 


Fig.  .335. 

of    the    outlines     of    the    the    food 

stomach  of  a  cat,  imme-  i  i       i     c         •  -in 

diately  after  a  meal  (11.0),  squeezed  back,  lormmg  an  axial  reflux  stream 
at  various  intervals  after-  towards  the  cardiac  end.  These  contractions 
TsiLtionof 'cisophageli  '^st  throughout  the  whole  period  of  gastric 
opening ;  yz,  '  transverse  digestion,  and  become  more  marked  as  diges- 

bancl '  ;     wx,   junction    of    ,•  j  mi.    •        ss     i.   •     i.      x,   '         j.i 

cardiac  and  pyloric  por-   ^lon  proceeds.     Their  effect  IS  to  bring  the 

tions.    (W.  B.  Cannon.)     whole  of  the  food  in  close  contact  with  every 

particle  of  pyloric  mucous  membrane  and  to  cause  a  thorough  mixture 

of  food  and  gastric  juice.     At  varying  periods  after  a  meal,  according 

782 


THE  MOVEMENTS  OF  THE  STOMACH  783 

to  the  nature  of  the  food  taken,  the  arrival  of  one  of  these  waves  of 
contraction  at  the  pylorus  causes  a  relaxation  of  the  orifice,  and 
a  few  cubic  centimetres  of  gastric  contents  are  squirted  into  the 
first  part  of  the  duodenum.  While  these  movements  of  the  pyloric 
mill  are  going  on,  the  cardiac  portion  of  the  stomach  is  exercising  a 
steady  pressure  on  its  contents  in  consequence  of  a  tonic  contraction 
of  its  muscular  wall,  so  that  each  successive  portion  of  the  food 
mass  which  is  loosened  by  the  digestive  action  of  the  gastric  juice 
is  forced  on  into  the  pyloric  mill.  As  digestion  proceeds  the  opening 
of  the  pylorus  becomes  more  frequent.  The  stomach  empties  itself 
more  and  more,  until  finally  the  whole  of  the  viscus  has  the  shape 
of  a  curved  tube  (Fig.  335).  At  the  very  end  of  digestion  the  pylorus 
may  open  to  allow  the  passage  even  of  undigested  morsels  of  food. 

Very  similar  are  the  changes  in  the  human  stomach,  as  shown  by 
Hertz.  The  term  fundus  is  by  him  limited  to  that  part  of  the 
stomach  situated  above  the  cardiac  orifice  (in  the  erect  position). 
The  hody  of  the  stomach  is  marked  off,  more  or  less,  by  the  incisura 
angularis  on  the  lesser  curvature  corresponding  to  what  we  have 
called  the  transverse  band.  The  pyloric  portion  consists  of  the 
pyloric  vestibule  and  the  pyloric  canal,  the  latter  being  a  tubular 
portion  about  3-0  cm.  in  length,  especially  well  marked  in  infants. 
When  a  small  quantity  of  food  has  been  swallowed  (in  the  erect 
position)  its  weight  is  sufficient  to  overcome  the  resistance  of  the 
contracted  gastric  wall,  and  it  rapidly  passes  to  the  pyloric  part. 
Peristalsis  begins  almost  at  once,  each  constriction  smarting  near 
the  middle  of  the  stomach,  and  deepening  as  it  slowly  progresses 
towards  the  pylorus  (Fig.  336).  About  one  inch  from  the  pyloric  canal 
it  is  so  marked  that  part  of  tht  pyloric  vestibule  becomes  almost  com- 
pletely separated  from  the  rest  of  the  stomach.  The  part  thus  cut 
ofi  then  diminishes  in  size  in  every  direction,  part  of  its  contents 
being  forced  through  the  pyloric  canal,  while  the  remainder  escapes 
back  as  an  axial  reflux  stream  into  the  stomach.  The  waves  recur  at 
regular  intervals  of  fifteen  to  twenty  seconds,  and  three  or  four  are 
present  simultaneously.  They  continue  without  cessation  until  the 
stomach  is  empty — from  one  to  four  hours  after  the  meal  according 
to  its  bulk  and  composition. 

The  foregoing  descriptions  apply  especially  to  the  events  which 
succeed  the  taking  of  a  considerable  meal.  If  warm  fluid  alone. 
e.g.  water,  be  swallowed,  the  opening  of  the  pylorus  occurs  within 
a  very  short  time  after  the  fluid  has  reached  the  stomach.  Thus  if 
a  large  draught  of  water  be  taken  to  quench  thirst  it  may  arrive 
in  the  duodenum  within  a  minute  or  two  after  being  swallowed,  and 
it  is  from  the  duodenum  and  small  intestine  that  any  absorption 
takes   place.      When   a   meal   is   undergoing    digestion,   there   is    a 


784 


PHYSIOLOGY 


distinct  relation  between  the  amount  of  acid  present  in  the  gastric 
contents  and  the  opening  of  the  pylorus.  One  may  indeed  say  that 
acidity  of  the  gastric  contents  exercises  a  direct  inhibitory  stimulus 
on  the  pyloric  sphincter. 

These  movements  of  the  two  portions  of  the  stomach  may  be 
observed  also  on  anaesthetised  animals  and  even  on  a  stomach  which 
has  been  excised  and  placed  in  warm  salt  solution.  They  must 
therefore  have  their  origin  in  the  walls  of  the  stomach  itself.  Although 
the  co-ordination  between  the  two  parts  of  the  stomach,  between 


Fig.  336.     Sketch  of  human  stomach,  iia  erect  position,  shortly  after  a 

bismuth  meal.     (Hertz.) 

F,   fundus  ;    u,   umbilicus  ;    lA,   incisura  angularis ;    PC,  pyloric  canal ; 

o,  oesophagus. 

the  tonic  contractions  of  the  fundus  and  the  rhythmic  contractions 
of  the  pyloric  part,  may  be  carried  out  by  the  local  nervous  system 
— Auerbach's  plexus — situated  between  the  layers  of  the  muscular 
coat,  it  is  probable  that  the  advancing  waves  of  contraction  observed 
in  the  antrum  are  myogenic,  i.e.  directly  originated  in  and  determined 
by  the  muscle  fibres  themselves.  We  have  no  direct  evidence  that 
these  movements  persist  after  throwing  the  local  nervous  system  out 
of  action ;  yet  it  is  evident  that  they  do  not  partake  of  the  nature 
of  a  true  peristalsis,  since  they  are  not  preceded  by  a  wave  of 
relaxation.  The  opening  of  the  pylorus,  on  the  other  hand,  which 
occurs  at    increasingly  frequent    intervals  at  the  end   of    a  wave, 


THE  MOVEMENTS  OF  THE  STOMACH  785 

must  be  ascribed  to  a  nervous  mechanism.  Although  the  local 
mechanism  probably  plays  the  greater  part  in  this  act  of  relaxation, 
the  normal  emptying  of  the  stomach  is  also  largely  dependent 
on  the  integiity  of  the  connection  of  this  viscus  with  the  central 
nervous  system.  If  both  vagus  nerves  be  divided  in  a  dog  below 
the  point  at  which  they  give  off  their  branches  to  the  lungs 
and  heart,  a  large  amount  of  food  may  remain  in  the  stomach  in 
an  undigested  condition.  The  secretion  of  gastric  juice  is  deficient, 
and  the  opening  of  the  pylorus  is  not  easily  carried  out.  Such  dogs 
therefore  tend  to  die  of  saprsemia,  being  poisoned  by  the  absorption 
of  products  of  putrefaction  from  the  gastric  contents.  Pawlow  has 
shown  that  animals  can  be  kept  ahve  for  months  after  division  of 
both  vagi  if  a  gastric  fistula  be  made,  the  animals  be  carefully  fed, 
and  care  be  taken  to  wash  out  adherent  non-digested  portions  of  food 
from  the  stomach. 

The  opening  of  the  pylorus  depends  not  only  on  intragastric 
events  but  also  on  the  condition  of  the  duodenum.  It  has  been 
shown  by  Serdjukow  that  the  pylorus  remains  firmly  closed  so 
long  as  the  contents  of  the  duodeniun  are  acid.  If  alkaline  fluid 
be  introduced  into  the  stomach,  this  is  rapidly  passed  into  the  duo- 
denum. If,  however,  some  acid  be  introduced  at  the  same  time  into 
the  duodenum  by  means  of  a  duodenal  fistula,  the  pylorus  remains 
firmly  closed,  and  no  fluid  passes  into  the  duodenum  mitil  the  acid 
which  was  placed  there  has  been  neutralised  by  the  secretion  of 
pancreatic  juice  and  succus  entericus.  We  have  probably  in  the 
walls  of  the  alimentary  canal  a  local  nervous  mechanism  for  the 
movements  of  the  pyloric  sphincter.  This  may  be  played  upon 
by  impulses  starting  either  in  the  stomach  or  in  the  duodenum, 
probably  by  the  contact  of  acid  with  the  mucous  membrane.  In- 
creasing acidity  on  the  side  of  the  stomach  causes  relaxation  of  the 
orifice,  whereas  acidity  on  the  duodenal  side  causes  contraction  of 
the  pyloric  sphincter.  The  exact  parts,  however,  played  in  this 
mechanism  by  the  local  system  and  by  the  central  nervous  system 
respectively  have  not  yet  been  thoroughly  made  out,  though  there 
is  no  doubt  that  these  movements  may  proceed  independently  of  any 
connection  with  the  central  nervous  system. 

Stimulation  of  the  peripheral  end  of  the  vagus  nerves  may  exercise 
varying  effects  on  the  stomach  wall  as  well  as  on  its  sphhicters.  In 
the  normal  animal  stimulation  of  tlie  peripheral  end  of  the  vagus  as 
a  rule  causes  strong  contractions  of  the  oesophagus  as  well  as  of  the 
cardiac  sphincter.  After  the  administration  of  atropine,  stimulation 
of  the  same  nerve  will  occasion  dilatation  of  the  cardiac  sphincter. 
On  both  cardiac  and  pyloric  portions  of  the  stomach  the  vagus 
exercises  inhibitory  as  well  as  augmentor  effects.     So  far  as  ct)ncerns 

50 


786 


PHYSIOLOGY 


the  musculature  of  the  fundus  or  body  of  the  stomach,  the  most 
usual  effect  is  an  inhibition  during  stimulation  of  the  vagus  succeeded 
by  an  augmented  tonus  immediately  the  stimulus  is  removed.  If 
the  vagus  be  excited  a  number  of  times  the  tonus  of  the  muscular 
wall  augments  with  each  stimulus.  On  the  pyloric  portion  stimula- 
tion of  the  vagus  also  causes  inhibition,  followed  bv  contraction. 


Fig.  337.  Distribution  of  the  vagus  in  the  abdomen  of  the  clog. 
(xM.  H.  Naylor.) 
RV,  LV,  right  and  left  vagi.  The  right  vagus  runs  behind  the  oesophagus 
(Oe)  and  stomach  (St),  and  in  those  places  is  represented  by  a  discontmuous 
line.  Cb,  connecting  branch  between  right  and  left  vagi ;  P,  pancreas  ;  Dd, 
duodenum  ;  FDJ,  flexura  duodeno-jcjunalis  ;  I,  I,  1,  intestine  ;  L,  liver  ; 
K,  kidney  ;  A,  suprarenal  capsule  ;  RG,  LG,  right  and  left  crura  of  (liaphragm  ; 
L.Sy.Ch,  left  sympathetic  chain;  12  D,  13  D,  twelfth  and  thirteenth  dorsal 
ganglia  ;  3  L,  third  lumbar  ganglion  ;  G.Sp.N,  L.Sp.N,  great  and  small 
splanchnic  nerves  ;  S.G,  left  semilunar  and  superior  mesenteric  ganglia  ; 
D.A,  dorsal  aorta. 

The  inhibition  may,  however,  be  very  short  and  in  rare  cases  altogether 
absent,  so  that  during  the  excitation  this  inhibition  is  followed  by 
a  series  of  large  rhythmic  contractions.  The  prevailing  motor  effect 
of  the  vagus  therefore  is  in  the  fundus  increased  tonus,  in  the  pyloric 


THE  MOVEMENTS  OF   THE   STOMA.CH  787 

portion  augmented  peristaltic  waves.  On  the  pylorus  itself  we 
may  obtain  from  vagal  stimulation  either  increased  or  diminished 
contraction.  The  conditions  under  which  each  of  these  may  be 
evoked  have  not  yet  been  definitely  ascertained.  Whether  the 
splanchnic  nerve,  i.e.  the  sympathetic  system,  has  a  direct  influence 
on  the  movements  of  the  stomach  has  been  disputed.  According  to 
Page  May  any  effect  produced  by  stimulation  of  this  nerve,  generally 
consisting  in  diminished  motor  activity,  is  probably  due  to  the 
simultaneous  influence  on  the  vascular  supply  to  the  organ  ;  the 
blood-vessels  being  constricted,  an  artificial  anaemia  is  produced 
which  in  itself  is  sufficient  to  account  for  diminished  activity.  Other 
observers  regard  the  splanchnic  as  having  an  influence  on  the  stomach 
similar  to  its  action  on  the  intestine,  and  regard  it  as  the  chief  inhibitory 
nerve  to  this  organ.  It  is  possible  that  the  extent  to  which  the 
stomach  is  brought  under  the  control  of  the  sympathetic  system 
may  vary  in  different  species  of  animals. 


IJSTESTINAL  DIGESTION 

The  products  of  gastric  digestion,  after  being  worked  up  in  the 
pyloric  half  of  the  stomach,  are  passed  at  intervals  into  the  first  part 
of  the  duodenum.  Here  they  meet  the  secretions  of  three  glands, 
namely,  the  pancreas,  the  liver,  and  the  tubular  glands  of  the  intes- 
tine. In  addition  to  these  must  be  mentioned  the  secretion  of 
Brunner's  glands,  which  are  situated  at  the  very  beginning  of  the 
duodenum.  The  glands  of  Brunner  extend  only  over  about  half  to 
one  and  a  half  inches  in  the  carnivora,  such  as  the  dog  or  cat,  but 
in  the  herbivora  they  may  be  found  occupying  the  upper  six  inches 
of  the  intestine.  The  secretion  of  these  various  juices  is  practically 
simultaneous  and  is  aroused  by  the  very  act  of  entry  of  the  acid 
chyme  into  the  duodenum.  Although  they  co-operate  in  their  action 
on  the  food-stuffs,  it  will  be  convenient  to  deal  separately  with  each 
both  as  regards  their  action  and  the  mechanism  of  their  secretion. 


SECTION  V 

THE  PANCREATIC  JUICE 

Pure  pancreatic  juice  can  be  obtained  either  from  an  animal 
with  a  permanent  fistula  or  from  one  with  a  temporary  fistula  by  the 
injection  of  secretin  into  the  animal's  veins.  A  flow  of  pancreatic 
juice  may  also  be  produced  by  the  administration  of  pilocarpine. 
This  drug  acts,  however,  as  a  poison  on  many  tissues  of  the  body,  not 
confining  its  action  to  the  pancreas  or  even  to  the  secreting  glands. 
It  is  not  to  be  wondered  at  therefore  that  the  pancreatic  juice 
obtained  by  its  injection  differs  in  quality  from  that  obtained  by  the 
more  natural  method  of  injection  of  secretin.  The  average  com- 
position of  pancreatic  juice  is  shown  in  the  Table  on  p.  789. 

It  is  a  clear  or  slightly  opalescent  fluid,  strongly  alkaline  from 
the  presence  of  sodium  carbonate,   its  alkahnity  varying  between 

N  N  .  ,     .  . 

—and  —  NajjCOg.      It    is   therefore   about   as   alkaline   as   gastric 

juice  is  acid,  and  it  will  be  found  that  equal  quantities  of  gastric 
juice  and  pancreatic  juice  when  added  together  practically  ne'utrahse 
one  another.     The  proteins  of  the  juice  may  be  roughly  divided 

788 


THE  PANCREATIC  JUICE 


789 


A 

ii 

c 

Alkalinity  : 

N 
Number  of  c.c.    -^  NaOH  equal 

1 
f 

(«) 

ib) 

12-7 

12-4 

9 

.'S-o 

to  10  c.c.  juice 

I.e.  in  terms  of  Na  in  100  c.c. 

0-2921 

0-2852 

0-2587 

01 16(1 

Total  solids  in  100  c.c. 

1 
\ 

1-6        1 
1-56      / 

2-2.5 

...,    -1 

6-38 
6-40 

Total  proteins  in  100  c.c.     . 

0-5 

— 

4-8 

Ash  in  100  c.c. 

1 
1 

1  -00      ) 
0-92      ( 

1-00 

1-00 

1-3 

Chlorides  in  100  c.c.    . 

1 
\ 

0-28081 
0-2966  / 

— 

— 

0-2695 

Total  nitrogen    .... 

— 

— 

— 

0-735 

A.  Secretin  juice  from  tliree  dogs.     Sp.  gr.  1014. 

B.  Secretin  juice,  specimen  collected  at  beginning  [a),  and  at  end  (6). 

C.  Pilocarpine  juice. 


into  three  gToups,  a  small  amount  of  nucleo-protein  precipitated 
on  acidification,  a  protein  coagulating  at  55°  C,  and  another  at 
about  75°  C.  The  juice  tends  to  become  poorer  in  proteins  and 
richer  in  alkali  as  secretion  proceeds.  The  concentrated  juice  obtained 
by  injection  of  pilocarpin,  which  may  contain  as  much  as  6  per  cent, 
total  solids,  is  always  considerably  less  alkaline  than  the  more  dilute 
juice  got  by  injection  of  secretin.  The  most  interesting  and  important 
constituents  of  the  juice  are  its  ferments  or  precursors  of  ferments. 
The  juice  on  arrival  in  the  intestine  has,  or  develops,  an  effect  on 
all  three  classes  of  food-stuffs,  namely,  proteins,  fats,  and  carbo- 
hydrates. 

ACTION  ON  PROTEINS 
Although  the  digestive  action  of  pancreatic  juice  on  proteins 
was  pointed  out  by  Corvisart,  little  attention  was  paid  to  this  action 
either  by  Claude  Bernard  or  subsequent  authorities  until  Kiihne 
subjected  the  action  of  extracts  of  the  gland  to  a  thorough  investiga- 
tion. The  neglect  of  this  action  by  Claude  Bernard  must  be  ascribed 
to  the  fact  that  he  worked  with  pancreatic  juice.  It  has  been  shown 
more  recently  that  pancreatic  juice  as  secreted  is  free  from  proteo- 
lytic effects,  and  that  for  the  development  of  this  power  it  is  necessaiy 
that  some  change  should  be  brought  about  in  the  juice  itself,  namely, 
a  conversion  of  trypsinogen  into  trypsin.  This  change  under  normal 
circumstances  is  brought  about  directly  the  juice  enters  the  gut, 
by  the  action  of  a  substance — enterokinase— contained  in  the  succus 
entericus.     The    pancreatic    juice    thereby    acquires    a    proteolytic 


790  PHYSIOLOGY 

activity  superior  to  that  of  any  other  digestive  juice,  so  that  the 
proteins  of  the  food  undergo  a  very  thorough  disintegTation.  The 
different  constituents  of  the  protein  molecule  show  a  varying 
resistance  to  the  action  of  trypsin.  The  greater  part  of  the  molecule 
is  rapidly  broken  down  into  its  proximate  constituents,  namely, 
amino-acids.  and  the  same  change  is  undergone  by  the  albumoses 
and  peptones  resulting  from  the  gastric  digestion  of  proteins.  Within 
a  few  minutes  therefore  after  the  chyme  has  reached  the  small 
intestine  a  certain  amount  of  amino-acids  will  have  been  formed. 
Some  of  the  groups  present,  however,  a  resistance  to  disintegration. 
After  tryptic  digestion  for  a  few  hours  the  mixture  will  be  found 
still  to  contain  a  considerable  quantity  of  peptone,  which  in  con- 
sequence of  its  resistance  to  further  alteration  was  designated  by 
Kiihne  '  antipeptone."  The  antipeptone  of  Kiihne  certainly  included 
some  of  the  diamino-acids,  which  at  that  time  had  not  been  isolated. 
There  is  always  a  part,  however,  which  gives  the  biuret  reaction 
and  is  only  slightly  broken  down  after  the  prolonged  action  of 
trypsin  into  the  amino-acids.  Even  when  the  trypsin  has  acted 
for  weeks  and  the  biuret  reaction  has  entirely  disappeared,  the  mixture 
will  be  found  to  contain,  in  addition  to  the  separate  amino-acids, 
some  members  of  the  polypeptide  class,  composed  of  two  or  more 
molecules  of  amino- acid  united  together.  One  of  these  polypeptides 
has  been  isolated  by  Fisher  and  Abderhalden  from  the  products 
of  tryptic  digestion  of  the  protein  of  silk,  and  has  been  found  to 
contain  glycine,  alanine,  and  proline.  The  stages  therefore  in  tryptic 
digestion,  e.g.  on  fibrin,  may  be  set  out  as  follows  : 

(1)  After  one  hour's  digestion — soluble  coagulable  protein,  deutero- 
albumose,  peptone,  amino-acids,  with  a  small  amount  of  alkali  albumen 
produced  by  the  action  of  the  alkali  of  the  juice. 

(2)  After  digestion  for  one  day — deutero-albumose,  '  antipeptone,' 
amino-acids,  polypeptides. 

(3)  After  digestion  for  one  month — amino-acids,  polypeptides. 
Among  the  amino-acids  tyrosine  is  one  of  the  first  to  be  split 

off,  and  this  substance,  with  leucine,  was  among  the  earhest  known 
products  of  pancreatic  digestion.  The  action  of  trypsin  is  thus  seen 
to  resemble  very  closely  the  action  of  boiling  concentrated  hydro- 
chloric acid.  Like  the  latter  it  attacks  the  protein  molecule  at 
the  — CO — NH —  coupling,  introducing  water  at  this  point  and 
therefore  breaking  up  the  polypeptide  groupings  into  simple  amino- 
acids.  Why  it  always  leaves  a  certain  remnant  of  the  polypeptides 
unattacked  is  not  at  present  explained.  The  investigation  of  its 
action  on  the  polypeptides  has  shown  that  very  minute  differences 
in  the  grouping  of  the  molecule  may  determine  whether  or  not  the 
molecule  is  attacked  by  trypsin.      Apparently  it  will   only  attack 


THE  PANCREATIC  JUICE  791 

such  molecules  as  are  present  in  the  naturally  occurring  proteins. 
Thus  under  the  action  of  trypsin  the  followinf,^  polypeptides  undergo 
hydrolytic  dissociation  :  alanyl  glycine,  alanyl  alanine,  alanyl 
leucine  A ;  while  the  closely  similar  polypeptides  glycyl  alanine, 
glycyl  glycine,  alanyl  leucine  B  are  left  untouched. 

CONDITIONS  OF  TRYPTIC  ACTIVITY 
Since  the  pancreatic  juice  is  strongly  alkaline  it  might  be  expected 
that  trypsin  would  be  most  effective  in  an  alkaline  medium.  It 
must  be  remembered,  however,  that  the  alkaline  juice  when  secreted 
meets  the  correspondingly  acid  contents  discharged  from  the  stomach, 
and  that  the  resulting  mixture  is  practically  neutral.  This  neutrality 
exists  throughout  the  small  intestine,  the  reaction  of  the  contents 
of  the  gut  being  similar  to  that  of  a  fluid  containing  alkali  which 
has  been  saturated  by  the  passage  of  carbonic  acid,  viz.  alkahne 
to  such  indicators  as  methyl  orange,  and  acid  to  such  indicators  as 
phenylphthalein.  On  investigating  the  action  of  trypsin  outside 
the  body,  it  is  found  that,  at  any  rate  as  concerns  its  earher  stages, 
this  ferment  is  more  active  in  the  presence  of  sodium  carbonate.  It 
is  usual  to  make  up  an  artificial  digestive  mixture  by  dissolving 
commercial  trypsin  in  0-2  to  0-3  per  cent,  sodium  carbonate.  The 
optimum  amount  of  sodium  carbonate  depends  on  the  strength  of 
the  solution  in  trypsin  :  the  more  trypsin  present  the  higher  is  the 
optimimi  amount  of  sodium  carbonate.  It  is  stated  that  although 
an  alkaline  reaction  is  more  advantageous  for  the  earlier  stages  of 
tryptic  activity,  the  later  stages  take  place  best  in  a  neutral  medium. 
This  result  is  probably  due  to  the  fact  that  trypsin  in  alkaline  medium 
is  extremely  unstable,  so  that  when  prolonged  digestions  are  carried 
out  the  trypsin  would  be  rapidly  destroyed  if  the  medium  were 
strongly  alkaline.  The  destructibility  of  trypsin,  as  well  as  its 
action,  is  largely  affected  by  the  presence  of  proteins  or  their  diges- 
tion products  in  solution.  Bayliss  has  adduced  evidence  to  show 
that  when  trypsin  acts  upon  protein  it  enters  into  some  form  of 
combination  with  the  protein  molecule.  This  combination  protects 
the  trypsin  from  the  destructive  action  of  alkali.  The  velocity  of 
the  reaction,  which  takes  place  under  the  influence  of  trypsin,  gradually 
diminishes,  owing  probably  to  a  combination  of  the  trypsin  with  the 
products  of  digestion,  e.q.  with  the  peptones  or  amino-acids,  and  its 
consequent  removal  from  the  sphere  of  action.  If  by  any  means 
the  amino-acids  be  removed  the  action  of  the  trypsin  is  renewed. 
This  destruction  of  ferment  occurs  in  the  intestine  itself.  If  the 
intestinal  contents  be  collected  by  means  of  a  fistula  at  the  lower 
end  of  the  ileum,  they  show  little  or  no  proteol^-tic  activity.  The 
trypsin  is  therefore  an  extremely  active  ferment  which  carries  out 


792  PHYSIOLOGY 

its  function  of  protein  hydrolysis  at  the  upper  part  of  the  gut  and 
is  destroyed  before  reaching  the  lower  end. 

THE  ACTIVATION  OF  PANCREATIC  JUICE 
It  was  observed  by  Kiihne  that  extracts  of  the  fresh  pancreas 
did  not  develop  their  full  activity  for  some  considerable  time,  the 
development  being  aided  by  preliminary  treatment  with  a  weak 
acid.  When  a  pancreatic  fistula  is  made  according  to  Pawlow's 
method,  the  juice  obtained  always  presents  some  proteolytic  activity. 
It  was  shown  by  Pawlow  and  Chepowalnikoff  that  the  development 
of  the  activity  of  the  juice  was  due  to  the  action  of  a  constituent 
of  the  succus  entericus  which  they  named  enterokinase,  and  it  has 
since  been  found  that  if  care  be  taken  to  avoid  contact  of  the  juice 
with  the  mucous  membrane  surrounding  the  orifice  of  the  duct,  it 
is,  when  secreted,  entirely  inactive.  Pawlow  regarded  the  entero- 
kinase as  acting  like  a  ferment  on  the  precursor  of  trypsin,  namely, 
trypsinogen,  present  in  the  juice  as  secreted.  He  named  this  body 
therefore  the  '  ferment  of  ferments.'  This  view  of  the  action  of 
enterokinase  has  been  challenged,  especially  by  Delezenne,  according 
to  whom  there  is  an  actual  combination  between  the  enterokinase 
and  the  trypsinogen,  trypsin  itself  being  a  mixture  or  combination 
of  the  two  bodies.  He  compared  their  action  to  that  of  the  hsemo- 
lysins,  which,  as  is  well  known,  involve  in  their  action  the  co-operation 
of  two  bodies,  the  amboceptor  and  the  complement.  If  this  were 
correct  there  should  be  always  a  proportionaUty  between  the  quanti- 
ties of  trypsinogen  and  enterokinase  respectively  which  are  necessary 
to  form  trypsin.  It  has  been  shown  by  Bayhss  and  Starling  that 
this  proportionality  is  not  present.  The  smallest  quantity  of  entero- 
kinase is  sufficient  to  activate  any  amount  of  trypsinogen  if  sufficient 
time  be  allowed.  The  effect  of  increasing  or  diminishing  the 
amount  of  enterokinase  is  not  to  alter  the  total  amount  of  trypsin 
finally  produced,  but  merely  the  time  taken  for  its  production.  This 
behaviour  characterises  a  ferment,  and  we  may  therefore  conclude 
that  the  view  originally  put  forward  by  Pawlow  is  correct,  namely, 
that  trypsin  is  produced  from  trypsinogen  under  the  action  of  a 
ferment  enterokinase.  This  is  not  the  only  method  by  which  the 
conversion  of  trypsinogen  into  the  active  ferment  can  be  brought 
about.  If  pancreatic  juice  be  allowed  to  stand,  even  with  the  addition 
of  toluol  to  prevent  bacterial  infection,  it  gradually  acquires  a  certain 
degree  of  activity.  If,  however,  sodium  fluoride  be  used  as  an 
antiseptic  the  juice  remains  permanently  inactive.  The  spontaneous 
activation  of  the  juice  may  be  hastened  by  neutralisation.  The 
most  potent  means  next  to  enterokinase  is  the  addition  of  lime  salts. 
If  a  few  drops  of  10  per  cent,  calcium  chloride  solution  be  added 


THE  PANCREATIC  JUICE  793 

to  fresh  pancreatic  juice,  the  calcium  being  in  such  a  quantity  as 
to  suffice  to  combine  with  all  the  carbonate  present  in  the  juice, 
complete  activation  of  the  juice  occurs  within  a  couple  of  days,  no 
further  increase  in  its  digestive  powers  being  obtained  on  subsequent 
addition  of  enterokinase.  It  has  been  suggested  that  the  action  of 
calcium  is  in  some  way  to  assist  in  the  production  of  an  enterokinase 
from  some  precursor  of  this  body  already  present  in  the  juice.  There 
is  no  doubt,  however,  that  the  two  kinds  of  activation  of  the  juice 
are  entirely  independent.  Enterokinase  will  activate  the  juice  in 
the  entire  absence  of  any  lime  salts,  e.g.  in  the  presence  of  excess  of 
sodium  fluoride  or  of  ammonium  oxalate.  After  lime  salts  have 
activated  a  juice  no  enterokinase  can  be  found  in  the  activated  juice, 
i.e.  it  has  no  power  of  activating  fresh  portions  of  pancreatic  juice. 
The  mode  in  which  calciimi  salts  act  is  not  at  present  understood. 
If  they  have  once  been  removed  from  the  pancreatic  juice  it  is  not 
possible  to  reinduce  activation  by  the  subsequent  addition  of  excess 
of  lime  salts.  We  must  therefore  conclude  that  the  lime  salts  are 
present  in  some  form  of  combination  which  is  destroyed  by  decalci- 
fication, the  change  involved  in  the  destruction  being  irreversible, 
so  that  the  original  condition  cannot  be  restored  by  the  subsequent 
addition  of  lime  salts.  It  is  not  likely  that  this  calcium  activation 
plays  any  part  in  the  normal  processes  of  digestion.  For  its  com- 
pletion it  needs  twelve  to  sixteen  hours,  whereas  the  enterokinase 
present  in  the  succus  entericus  will  effect  the  activation  of  the  juice 
within  a  few  minutes.  The  action  of  calcium  salts  at  present  must 
be  regarded  as  merely  of  theoretical  significance. 

THE  ACTION  OF  PANCREATIC  JUICE  ON  MILK 
On  the  addition  of  pancreatic  juice  to  milk  a  clot  is  produced 
which  speedily  redissolves.  If  re-solution  takes  place  too  rapidly 
the  production  of  a  formed  clot  may  be  missed.  In  every  case, 
however,  on  heating  the  milk  a  few  minutes  after  the  addition  of 
the  trypsin  a  clot  is  obtained.  How  far  this  action  is  to  be  ascribed 
to  the  proteolytic  ferment  trypsin,  or  how  far  it  is  due  to  the 
presence  of  a  free  rennet-like  ferment  in  the  juice,  is  not  yet  definitely 
settled.  Since  the  rennet  action  is  parallel  to  the  proteolytic  activity 
of  the  juice,  it  is  probable  that  we  must  regard  the  clotting  of  milk 
as  the  first  stage  in  its  proteolysis. 

THE   ACTION  OF  PANCREATIC  JUICE   ON 

CARBOHYDRATES 

The  pancreatic  juice,  as  well  as  fresh  extracts  of  the   pancreas 

itself,  contains  a   strong   amylolytic    ferment,  diastase,  amylase,  or 

araylopsin.     If  a  few  drops  of  pancreatic  juice  be  added  to  a  1  per 


794  PHYSIOLOGY 

cent,  solution  of  boiled  starch,  within  a  few  seconds  the  solution  clears, 
and  in  half  a  minute,  on  the  addition  of  iodine,  a  red  colour  is  obtained, 
showing  the  presence  of  erythrodextrin.  At  the  end  of  a  few  minutes 
no  colour  is  obtained  w^ith  iodine,  and  the  solution  contains  maltose. 
The  stages  in  the  hydrolysis  of  starch  brought  about  with  pancreatic 
juice  are  exactly  similar  to  those  effected  by  ptyaUn.  If  the  juice  be 
neutralised,  it  is  found  that  the  process  of  hydrolysis  goes  on  to  the 
formation  of  dextrose  or  glucose.  This  further  conversion  is  due 
to  the  presence  in  the  juice  of  a  second  ferment— maltase — which 
converts  the  disaccharide  maltose  into  the  monosaccharide  glucose. 
The  juice  in  the  gut  is  therefore  able  to  effect  the  further  digestion 
of  the  products  of  salivary  digestion.  On  the  other  disaccharides 
pancreatic  juice  is  without  effect.  It  contains  no  invertase,  nor 
does  it,  in  spite  of  certain  statements  to  the  contrary,  ever  contain 
lactase.     It  has  therefore  no  effect  on  either  cane  sugar  or  milk  sugar. 

THE  ACTION  OF  PANCREATIC  JUICE  ON  FATS 
Fresh  pancreatic  juice  contains  a  strong  lipase  or  fat-splitting 
ferment,  by  means  of  which,  in  the  presence  of  water,  neutral  fats, 
e.g.  the  triglycerides  of  palmitic,  stearic,  and  oleic  acids,  are  broken 
up  into  glycerin  and  the  corresponding  fatty  acids.  This  ferment 
is  active  either  in  alkaline,  neutral,  or  very  slightly  acid  reaction. 
If  the  reaction  be  alkaline  the  fatty  acids  produced  by  the  lipolysis 
combine  with  the  alkali  present  with  the  formation  of  soaps.  The 
ferment  may  be  obtained  from  extracts  of  the  fresh  gland,  but  is 
rapidly  destroyed  if  active  trypsin  be  present.  It  is  also  contained 
in  some  of  the  dried  commercial  preparations  of  trypsin.  It  is 
apparently  insoluble  in  distilled  water,  and  is  therefore  found  in 
the  residue  after  extracting  these  commercial  preparations  with 
water.  It  is  easily  soluble  in  glycerin.  The  velocity  with  which 
lipolysis  occurs  is  much  increased  (four  to  five  times)  by  the  addition 
of  bile.  This  adjuvant  action  of  bile  is  not  destroyed  by  boihng, 
and  is  due  entirely  to  the  bile  salts.  These  act  in  two  ways.  In  the 
first  place,  by  their  physical  qualities  they  diminish  the  surface  tension 
between  water  and  oil,  so  enabling  a  closer  contact  to  be  effected 
between  the  watery  solution  contained  in  the  juice  and  the  oil  which  is 
presented  to  it.  Moreover  they  may  aid  in  the  solution  of  the  ferment 
itself.  In  the  second  place,  bile  salts  have  a  solvent  action  on  soaps 
as  well  as  on  fatty  acids  in  slightly  acid  medium.  Bile  may  be  regarded 
therefore  as  a  favourable  excipient  or  medium  for  the  interaction  of 
the  lipase  and  the  neutral  fats.  The  lipase  of  pancreatic  juice  will 
also  hydrolyse  the  esters  of  the  fatty  acids,  such  as  ethyl  butyrate 
or  monobutyrin.  On  the  phosphorised  fats  or  phosphatides,  such  as 
lecithin,  its  action  is  still  a  subject  of  doubt.     According  to  certain 


THE  PANCREATIC  JUICE  795 

authors  extracts  of  the  pancreas  have  the  power  of  splitting  off 
choline  from  lecithin.  It  is  not  kno^\Ti  whether  the  same  property 
is  present  in  pancreatic  juice  itself,  or  whether  any  other  dissociations 
are  brought  about  in  the  complex  molecule  of  lecithin  under  the 
action  of  this  digestive  fluid. 

THE  SECRETION  OF  PANCREATIC  JUICE 
In  order  to  study  the  relation  of  the  secretion  of  pancreatic  juice 
to  the  other  processes  of  digestion,  observations  must  be  carried 
out  on  an  animal  with  a  permanent  pancreatic  fistula.  Such  a 
fistula  was  established  bv  Claude  Bernard  by  bringing  the  duct  of 
the  pancreas  to  the  surface  and  inserting  into  it  a  lead  or  silver  tube. 
The  arrangement  was,  however,  unsatisfactory  since  after  a  few  days 
the  tube  dropped  out  and  the  natural  course  of  the  duct  from  pan- 
creas to  intestine  was  restored.  In  order  to  avoid  the  disadvantages 
of  this  proceeding  Heidenhain  and  Pawlow  independently  devised 
another  method  to  enable  us  to  determine  the  causes  of  pancreatic 
secretion.  The  pancreas  in  most  cases  possesses  two  ducts,  the 
upper  one  opening  along  with  the  bile  duct,  the  lower  one  a  short 
way  down.  The  relative  sizes  of  these  two  ducts  vary  in  different 
animals,  the  lower  one  being  larger  in  the  dog,  while  in  man  and 
the  cat  the  upper  one  is  the  larger.  In  order  to  establish  a  pan- 
creatic fistula  in  a  dog,  a  small  quadrilateral  piece  of  the  duodenal 
wall  is  exsected,  ha\nng  the  papilla  of  the  lower  duct  opening  in  the 
middle  of  its  mucous  surface.  The  integrity  of  the  gut  is  restored 
by  suturing  in  a  single  line  of  stitches  the  margins  of  the  wound 
in  the  duodenum,  and  the  exsected  piece  is  brought  to  the  surface 
and  stitched  in  the  middle  of  the  abdominal  wound.  The  greater 
part  of  the  pancreatic  secretion  will  escape  by  the  fistula,  and  can 
be  collected  either  by  the  insertion  of  a  cannula  into  the  duct  or  by 
attaching  a  glass  funnel  below  its  orifice.  Great  care  has  to  be  taken 
in  the  after  treatment  of  such  animals.  The  pancreatic  juice,  which 
flows  over  the  papilla,  acquires  in  so  doing  strong  proteolytic  powers, 
and  tends  therefore  to  dissolve  and  irritate  the  adjacent  abdominal 
wall.  This  can  be  prevented  by  taking  care  to  collect  all  the  juice, 
and  to  allow  none  to  flow  away  over  the  surface  of  the  body.  Another 
drawback  is  that  the  contiiuial  loss  of  pancreatic  juice  in  many  cases 
seriously  affects  the  animal's  health.  This  may  be  obviated  to  a 
certain  extent  by  keeping  the  animal  on  a  milk  diet  vrith.  the  addition 
of  sodium  bicarbonate  to  replace  the  loss  of  this  salt  by  the  juice. 
With  great  care  Pawlow  has  succeeded  in  keeping  such  animals  in 
a  perfectly  healthy  condition.  In  the  fasting  condition  there  is, 
as  a  rule,  no  secretion  of  juice,  though  the  escape  of  a  few  drops  may 
be  observed  at  ionjr  intervals.     If  a  meal  be  administered  to  the 


796  PHYSIOLOGY 

animal,  a  flow  of  juice  begins  in  one  to  one  and  a  half  minutes.  From 
this  time  there  is  a  steady,  slow  rise  of  the  rate  of  secretion,  which 
lasts  for  two  to  three  hours,  and  then  gradually  diminishes.  The 
greatest  increase  in  flow  is  observed  at  the  time  when  the  first  por- 
tions of  digested  food  escape  from  the  stomach  into  the  duodenum. 
The  secretion  must  therefore  be  determined  in  some  way  by  the 
entry  of  this  food  into  the  duodenum.  By  experiments  on  dogs 
possessing  a  gastric  as  well  as  a  pancreatic  fistula,  it  has  been  shown 
that  the  introduction  of  acid,  e.g.  0-4  per  cent.  HCl,  into  the  stomach 
evokes,  as  soon  as  it  passes  into  the  duodenum,  a  rapid  flow  of  pan- 
creatic juice.  A  similar,  but  smaller,  effect  is  produced  by  the 
passage  of  oil  from  the  stomach  into  the  duodenum.  The  intro- 
duction of  alkalies  is  without  effect.  Weak  acids  are  also  effective 
exciters  of  secretion  if  they  be  introduced  directly  into  the  duodenum 
itself  or  into  a  loop  of  small  intestine.  The  effect  gradually  diminishes 
as  the  loop  which  is  chosen  comes  nearer  to  the  caecum,  and  as  a  rule 
the  injection  of  dilute  acid  into  the  lower  foot  or  eighteen  inches 
of  ileum  is  without  effect  on  the  pancreas.  The  striking  resemblance 
between  the  secretion  thus  evoked  and  that  produced  in  the  saHvary 
glands  by  injection  of  acid  into  the  mouth  suggests  that  we  have 
here  to  do  with  a  reflex  of  the  same  kind  as  that  which  affects  the 
salivary  glands.  In  the  search  for  the  channels  of  this  reflex  Heiden- 
hain  showed  that  stimulation  of  the  medulla  oblongata  occasionally 
produced  a  flow  of  pancreatic  juice.  He  was  unable,  however, 
to  obtain  any  secretion  on  stimulation  of  the  vagus  nerve. 
The  pancreas  receives  fibres  from  the  vagi  as  well  as  from  the 
splanchnic  nerves  (sympathetic  system).  According  to  Pawlow 
the  ill  success  of  Heidenhain's  experiments  was  due  to  the  fact  that 
in  any  operation  a  gland  is  played  upon  by  reflex  impulses  partly 
of  an  inhibitory,  partly  of  a  secretory  nature,  in  which  the  inhibitory 
predominate,  and  by  the  further  fact  that  the  pancreas  is  extremely 
susceptible  to  alterations  in  its  blood -supply,  so  that  any  stimula- 
tion of  the  vagus  which  caused  inhibition  of  the  heart  would 
ipso  facto  prevent  the  effect  of  simultaneous  excitation  of  secretory 
fibres  from  making  its  appearance.  Pawlow  noticed  that  if  in  an 
animal  with  a  permanent  fistula  the  vagus  on  one  side  were  cut 
and  left  for  four  days  in  order  to  allow  the  cardio-inhibitory  fibres 
to  degenerate,  repeated  stimulation  of  the  peripheral  end  of  the 
nerve  evoked  a  flow  of  pancreatic  juice.  He  obtained  the  same 
results  by  stimulating  this  nerve  below  the  point  at  which  it  had 
given  off  its  cardio-inhibitory  fibres,  in  animals  in  which  the  reflex 
inhibitions  from  the  operation  itself  were  prevented  by  total  section 
of  the  medulla.  Under  certain  circumstances  he  obtained  also 
secretion   on   stimulation   of    the   splanchnic   nerves,   and   therefore 


THE  PANCREATIC  JUICE  797 

concluded  that  these  two  nerves — splanchnics  and  vagi — ^were  the 
efferent  channels  in  the  reflex  secretion  set  up  by  the  introduc- 
tion of  the  acid  into  the  duodenum.  It  was  shown  later,  however, 
independently,  both  by  Popielski,  a  pupil  of  Pawlow,  and  by 
Wertheimer,  that  the  injection  of  acid  into  a  loop  of  small  intestine 
was  followed  by  secretion  of  juice  even  after  section  of  both  vagi 
and  destruction  of  the  sympathetic  ganglia  at  the  back  of  the  abdominal 
cavity.  On  repeating  these  experiments  Bayliss  and  Starling  found 
that  a  secretion  of  juice  was  produced  even  when  the  acid  was  intro- 
duced into  a  loop  of  the  small  intestine  entirely  freed  from  any 
possible  nervous  connections  with  the  rest  of  the  body.  It  was 
evident  therefore  that  the  stimulus  or  message  from  the  intestine 
to  the  pancreas  which  causes  the  secretion  of  the  latter  must  be 
carried,  not  by  the  nervous  system,  but  by  the  blood  stream.  Since 
the  injection  of  acid  into  the  portal  vein  was  without  effect  on  the 
pancreas,  it  was  evident  that  something  must  be  produced  in  the 
epithelial  cells  of  the  gut  under  the  influence  of  acid,  and  that  this 
product  of  the  epithelial  cells  was  absorbed  in  the  blood  stream  and 
was  the  active  agent  in  exciting  the  pancreas.  On  pounding  up 
some  scrapings  of  the  intestinal  mucous  membrane  with  dilute 
hydrochloric  acid  and  filtering,  and  injecting  the  filtrate,  a  copious 
flow  of  pancreatic  juice  was  produced.  This  chemical  messenger 
or  hormone  from  the  intestine  to  the  pancreas  is  called  '  secretin,' 
or  '  pancreatic  secretin  '  to  distinguish  it  from  possible  other  members 
of  the  same  class.  It  is  produced  in  the  mucous  membrane  from 
a  precursor — pro-secretin.  The  latter  has  not  been  isolated,  but  that 
it  is  present  in  the  mucous  membrane  is  shown  by  the  fact  that 
secretin  can  be  extracted  by  the  action  of  acids  from  mucous  membrane 
which  has  been  killed  by  heat  or  by  the  prolonged  action  of  alcohol. 

Secretin  itself  is  not  a  ferment.  In  order  to  prepare  it  the  mucous 
membrane  is  ground  up  with  sand,  boiled  with  0-4  per  cent,  hydro- 
chloric acid,  and  then  neutralised  while  boilina  bv  the  cautious 
addition  of  sodium  hydrate.  The  coagulable  proteins  are  in  this 
way  precipitated,  and  the  filtered  solution  contains  the  secretin. 
It  is  not  precipitated  by  the  ordinary  alkaUne  reagents,  and  diffuses 
slowly  through  animal  membranes.  Though  stable  in  acid  solutions, 
it  is  very  rapidly  destroyed  in  alkaline  or  neutral  solutions,  especially 
under  the  influence  of  bacteria.  It  is  apparently  oxidised  with 
extreme  ease.  A  similar,  or  more  probably  the  same,  body  may  be 
produced  from  intestinal  mucous  membrane  by  treating  this  with 
solutions  of  soap. 

In  this  secreting  mechanism  we  have  a  very  striking  example 
of  a  correlation  between  the  activities  of  two  different  portions  of 
the  body  effected  by  chemical  means.     The  strongly  acid  chjTne 


798  PHYSIOLOGY 

enters  the  first  part  of  the  duodenum.  *  Immediately  a  certain  amount 
of  secretin  is  produced  by  the  acid  in  the  cells  of  the  mucous  membrane. 
The  secretin  is  carried  by  the  blood  stream  to  the  cells  of  the  pancreas 
and  excites  there  the  secretion  of  strongly  alkaline  pancreatic  juice. 
As  soon  as  sufiicient  juice  has  been  secreted  to  neutrahse  the  acid 
chyme  the  formation  of  secretin,  and  therefore  the  further  secretion 
of  pancreatic  juice,  comes  to  an  end.  If  the  stomach  still  contains 
food  the  process  is,  however,  renewed  in  virtue  of  the  local  reflex 
mechanism  which  we  have  just  studied  regulating  the  opening  and 
closure  of  the  pylorus.  So  long  as  the  contents  of  the  duodenum 
are  acid  the  pylorus  remains  firmly  closed.  As  soon  as  these  are 
neutraUsed  the  pylorus  relaxes  and  allows  the  entrance  of  a  further 
portion  of  acid  chyme.  Thus  the  formation  of  secretin  proceeds 
afresh,  and  the  whole  chain  of  processes  goes  on  until  the  stomach 
is  empty  and  all  its  contents  have  passed  into  the  intestine. 

In  view  of  the  efficacy  of  this  chemical  reflex  mechanism,  the 
question  arises  whether  the  results  first  obtained  by  Pawlow  were 
really  due  in  some  way  to  the  formation  of  secretin.  Stimulation 
of  the  vagus  may  cause  contraction  of  the  stomach,  opening  or  closing 
of  the  pylorus,  and  it  seems  possible  that  under  its  action  there 
might  have  been  an  escape  of  acid  gastric  contents  into  the  intestine, 
and  therefore  the  formation  of  secretin,  which  would  sufiice  to  arouse 
the  pancreatic  secretion.  Later  experiments  by  this  observer,  in 
which  the  escape  of  any  gastric  contents  was  effectively  prevented 
by  ligature  of  the  pylorus  while  the  stomach  itself  contained  an 
alkahne  solution,  have  shown  that  even  with  these  precautions  a 
flow  of  juice  may  be  obtained  on  stimulation  of  the  vagus  nerve. 
The  flow,  however,  is  very  small  in  comparison  with  that  obtained 
by  injection  of  secretin,  and  one  must  conclude  that  although  the 
nervous  system  may  play  a  small  part  in  the  excitation  of  the  activity 
of  this  gland,  the  main  factor  involved  is  the  chemical  mechanism 
which  has  just  been  described. 

The  amount  of  pancreatic  juice  obtained  after  a  meal  varies 
with  the  nature  of  the  latter.  The  Table  on  p.  799  represents  the 
results  obtained  on  an  animal  fed  with  600  c.c.  of  milk,  250  grm. 
of  bread,  and  100  grm.  of  meat  respectively. 

The  differences  between  these  results  seem,  however,  largely 
determined  by  the  duration  of  gastric  digestion,  and  therefore  the 
amount  of  acid  secreted  in  the  stomach  and  passed  on  to  the  duodenum. 
It  was  suggested  by  Walther  that  apart  from  this  quantitative  adapta- 
tion there  was  a  quahtative  alteration  in  the  constitution  of  the 
juice  according  to  the  nature  of  the  food  ingested,  that,  e.g.,  excess 
of  protein  causes  an  increase  of  the  trypsin,  while  excess  of  carbo- 
hydrate would  cause  an  increase  in  the  amylase  of  the  juice.     Later 


THE  PANCREATIC  JUICE  799 

researches  have  failed  to  confirm  this  view.  Apparently  when  the 
pancreas  is  excited  to  secrete,  it  turns  out  its  various  ferments  in 
constant  proportion,  depending  on  the  amounts  of  these  already 
present  and  stored  up  in  the  gland. 

Skchktion  of  Pa>xreatic  Juice  (Walther) 


Hours  after  meal 

000  c.c.  milk 

250  grm.  bread 

100  grm.  meat 

1 

8-5  C.C. 

36-5  c.c. 

38-75  c.c. 

2 

7-6  c.c. 

50-2  c.c. 

44-6    c.c. 

3 

14-6  c.c. 

20-9  c.c. 

30-4    c.c. 

i 

11-2  c.c. 

14-1  c.c. 

16-9    c.c. 

5 

3-2  c.c. 

16-4  c.c. 

0-8    c.c. 

6 

1-0  c.c. 

12-7  c.c. 

— 

7 

— 

10-7  c.c. 

— 

8 

— 

6-9  c.c. 

1 

THE  STRUCTURAL  CHANGES  IN  THE  PANCREAS 

WHICH   ACCOMPANY  SECRETION 

The  ease  with  which  secretin  may  be  prepared  and  used  to  arouse 

the  activity  of  the  pancreas  has  rendered  it  possible  to  study  more 

closely  the  changes  which  in  this  gland  accompany  activity.     Kiihne 

and  Sheridan  Lee  succeeded  in  observing  the  gland  of  the  rabbit  in 


Fig.  338.     A  tciminal  lobule  of  the  pancreas  of  the  rabbit.     (Kuhne  and 

fcjHEKiDAN  Lea.) 

A,  in  resting  condition  ;  b,  after  active  secretion. 

a  living  state  under  the  microscope.  They  noted  that  activity, 
excited  by  pilocarpine,  was  associated  with  a  discharge  of  granules, 
a  clearing  up  of  the  cells,  and  a  diminution  in  size  and  the  appearance 
of  a  lumen  to  the  gland  alveoli  (Fig-  338).  A  normal  resting  gland  is  of 
an  opaque,  yellowish- white  colour,  and  of  firm  consistence.  On  section 
it  is  seen  to  consist  of  mmierous  secreting  alveoh  which  open  into 
narrow  intercalary  tubules,  and  these  in  their  turn  into  wide  collecting 
tubules.     The  lining  epithelium  of  the  intercalated  tubules  is  often 


800 


PHYSIOLOGY 


continued  into  the  secreting  part,  where  they  He  internal  to  the 
secreting  cells,  as  the  so-called  centro-acinar  cells.  The  secreting 
cells  themselves  present  two  well-marked  zones,  a  narrow  peripheral 
zone  in  which  the  nucleus  is  embedded,  which  is  strongly  basophile, 
and  a  central  part  which  is  turned  towards  the  liuuen,  occupying 
two-thirds  or  three-quarters  of  the  cell,  and  is  closely  packed  with 
highly  refractive  granules  strongly  acidophile  and  presumably  con- 
taining or  composed  of  the  precursors  of  the  various  constituents  of  the 
pancreatic  juice  (Fig.  339).     If  the  activity  of  the  gland  be  aroused  by 


B 


Fig.  339.     Alveoli  of  dog's  pancreas.     (Schafer.) 
A,  resting ;  b,  after  moderate  secretion  with  discharge  of  granules. 


injection  of  secretin  and  the  injection  be  continued  until  the  rate  of 
secretion  evoked  by  each  injection  diminishes  considerably,  i.e.  the 
gland  shows  signs  of  fatigue,  marked  changes  are  observed  both 
macroscopically  and  under  the  microscope.  The  gland  is  now  pink 
and  transparent  in  appearance,  moist  and  soft  in  consistence.  On 
section  the  kmien  of  each  alveolus  is  enlarged,  the  cells  are  shrunken, 
and  the  granules  are  found  to  lie  only  along  the  border  of  the  cell 
turned  towards  the  lumen,  the  rest  of  the  cell,  which  is  much  reduced 
in  size,  being  made  up  of  the  basophile  protoplasm.  So  far  the  changes 
resemble  those  already  described  for  the  sahvary  glands.  If,  however, 
the  injection  of  secretin  be  continued  until  no  more  secretion  is 
evoked,  the  histological  changes  in  the  cells  will  be  found  still  more 
marked.     We  have  long  known  of  the  existence  in  the  pancreas 


THE  PANCREATIC  JUICE  801 

of  islets  of  cells  known  as  *  Langerhans'  islets/  composed  of  epithelial 
celLs,*of  which  the  individual  members  take  any  stain  with  great 
difficulty,  so  that  the  islets  appear  as  unstained  areas  in  the  middle 
of  the  darlcly  stained  secreting  substance.  Tliese  islets  have  been 
looked  upon  as  structures  altogether  apart  from  the  secreting  tissue 
of  the  pancreas,  and  have  been  endowed  with  functions,  cq.  con- 
nected with  the  metabolism  of  carliohydrates,  quite  independent 
of  the  r'lJe  of  the  pancreas  in  digestion.  Dale  has  found,  however, 
that  these  islets  are  more  numerous  and  larger  in  a  dand  which  has 


Fig.  340.  Formation  ui  i^n'.  "l  j_>  hi-mihu?  nwm  .--i.  r:-;.  i  \  .m.  "li.  Part  of  the 
pancreas  of  a  toad  in  which  active  secretion  had  been  excited  by  injection  of 
secretin.  The  islet  of  Langerhans  -n-ith  its  unstained  hyaline  cells  presents 
a  marked  contrast  to  the  secretory  alveoli  trith  their  basophile  protoplasm 
and  deeph^  stained  zymogen  granules.  The  islet,  however,  is  increasing  in  size 
at  the  expense  of  the  secreting  tissue,  which  in  many  places  is  losing  all  its 
chromophile  elements.  In  the  middle  of  the  islet  is  some  of  the  secretory 
tissue  where  the  change  is  not  yet  complete.  (Drawn  from  a  micro-photograph 
of  a  specimen  by  H.  H.  D.\i.E.) 

been  actively  secreting.  In  the  completely  exhausted  gland  large 
tracts  of  the  secreting  tissue  are  foimd  to  have  lost  not  only  their 
acidophile  granules  but  also  the  whole  of  the  basophile  substance 
from  their  protoplasm,  so  that  they  are  indistinguishable  from  the 
cells  making  up  the  cells  of  the  islets  of  Langerhans.  Moreover  in  such 
specimens  the  islets  are  observed  to  be  actively  increasing  in  circum- 
ference (Fig.  340),  taking  in  one  alveolus  after  another  of  the  secreting 
tissue,  and  the  growth  of  the  islet  may  be  noted  often  by  the  fact 
that  it  includes  portions  of  the  alveoli  in  which  the  stage  of  exhaustion 
has  not  proceeded  to  such  a  great  extent,  so  that  the  cells  still  contain 

51 


802  PHYSIOLOGY 

some  zymogen  granules.  One  may  concliKle  that  the  islets  of 
Langerhans  represent,  not  a  tissue  siii  generis,  but  a  stage  in  the 
life  history  of  the  secreting  cells  of  the  pancreas.  Whether  they 
subsequently  build  up  basophile  material  and  from  this  new  granules, 
or  whether  they  are  cleared  away  to  be  replaced  by  newly  formed 
tissue,  we  do  not  know.  The  fact,  however,  that  in  the  embryo  a  large 
amount  of  the  pancreas  is  of  the  nature  of  islet  tissue  suggests  that 
the  islets  and  exhausted  cells  found  in  a  thoroughly  exhausted  gland 
may  later  on  undergo  regeneration  and  be  re-formed  into  secreting 
cells. 

This  conclusion  may  have  to  be  revised  in  the  light  of  more  recent  researches, 
especially  by  Bensley.  It  seems  to  be  generally  agreed  that  the  islets  may  be 
formed  tliroughout  life  by  growth  from  the  ducts  of  the  glands.  By  aj^propriate 
methods  they  may  be  shown  to  contain  fine  granules,  differing  altogether  in 
staining  reactions  from  the  zymogen  granvdes  of  the  secreting  acini.  According 
to  Bensley,  neither  the  number  nor  the  situation  of  the  specifically  stahied  islets 
undergoes  any  change  as  a  result  of  starvation  or  of  exhaustion  of  the  gland.  It 
must  be  acknowledged  that  Dale's  criteria  of  islet  tissue  were  chiefly  negative, 
and  that  unless  the  sections  be  treated  so  as  to  display  the  specific  granulation 
of  the  islet  tissue,  it  woiild  not  be  possible  to  distinguish  it  from  completely 
exhausted  secreting  cells,  which  had  lost  their  basophile  substance  as  well  as 
their  zymogen  granules.     The  question  cannot  be  regarded  as  finally  decided. 


SECTION  VI 

THE    BILE 

The  fact  that  the  bile,  the  secretion  of  the  hver,  is  in  so  many 
animals  pom'ed  into  the  intestine  by  an  orifice  common  to  it  and 
the  pancreatic  juice  suggests  that  these  two  fluids  co-operate  in 
their  actions  on  the  ingested  food-stufTs,  and  points  to  a  direct  use 
of  the  bile  in  the  processes  of  digestion.  In  addition  to  this  function, 
the  bile  must  also  be  regarded  as  an  excretion,  representing  as  it 
does  the  channel  by  which  the  products  of  disintegration  of  haemo- 
globin— ^the  red  colouring-matter  of  the  blood — are  got  rid  of  from 
the  organism.  As  an  excretion  the  production  of  bile  must  be 
continuous,  and  related,  not  to  the  processes  of  digestion,  but  to  the 
intensity  of  destruction  of  the  red  corpuscles.  On  the  other  hand, 
bile,  as  a  digestive  fluid,  is  needed  in  the  gut  only  during  the  period 
that  digestion  is  going  on.  The  exigencies  of  the  body  therefore 
require  a  continuous  excretion  of  bile  by  the  Uver,  but  a  discontinuous 
entry  of  this  fluid  into  the  small  intestine.  This  discontinuity  in  the 
entry  of  a  continuous  secretion  into  the  intestine  is  secured,  in  the 
majority  of  animals,  by  the  existence  of  the  gall-bladder,  a  diverti- 
culum from  the  bile -ducts,  in  which  all  bile,  secreted  dming  the 
intervals  between  the  periods  of  digestive  activity,  is  stored  up. 
In  the  horse,  where  the  gall-bladder  is  absent,  its  place  is  taken  to 
some  extent  by  the  great  size  of  the  bile -ducts.  Moreover  in  such 
an  animal  the  process  of  digestion  is  much  more  continuous  in  char- 
acter than  it  is  in  carnivora.  Since  the  bile  accumulates  in  the  gall- 
bladder during  the  whole  time  that  digestion  is  not  going  on,^and 
is  only  poured  into  the  gut  during  digestion,  in  a  fasting  animal 
the  gall-bladder  is  distended,  whereas  in  an  animal  some  hours  after 
a  meal  the  gall-l)ladder  is  practically  empty. 

During  the  period  that  the  bile  secreted  by  the  hver  renuiins 
in  the  gall-bladder  it  undergoes  certain  changes,  as  is  sliown  by 
comparison  of  the  composition  of  bile  obtained  from  the  gall-bladder 
with  that  obtained  from  a  fistula  of  the  bile-duct. 


803 


804 

PHYSIOLOGY 

Analyses  of  Bile  (Human) 

From  a  biliary  fistula 

(Yeo  and  Herroun) 

From  the  gall-l)latlder  (Hoppe 
in  100  parts 

-Seyler) 

Mucin  and  pigments 

.      0-148 

Mucin 

1-29 

Sodium  taiirocliolato 

0-055 

Sodium  taurocholate 

0-87 

Sodium  glycocholate 

0-165 

Sodium  glycocliolatr- 

303 

Cholesterin 

1 

Soaps . 

1-39 

Lecithin  . 

0-038 

Cholesterin 

0-35 

Fats 

Lecithin 

0-53 

Inorganic  salts 

0-840 

Fats   . 

0-73 

Water 

98-7 

During  its  stay  in  the  bladder  the  bile  is  concentrated  by  the 
loss  of  water  and  by  the  addition  to  it  of  mucin  or  nucleo-albumen, 
derived  from  the  cells  lining  the  bladder.  Of  the  other  constituents 
of  bile,  the  pigments  must  be  regarded  simply  as  waste  products. 
They  pass  into  the  intestine  and  are  there  converted  by  the  processes 
of  bacterial  reduction  into  stercobiHn,  which  is  excreted  for  the  most 
part  with  the  faeces,  a  small  proportion  being  absorbed  into  the 
blood-vessels  and  turned  out  in  a  more  or  less  altered  condition  as 
the  pigments  of  the  urine.  From  the  point  of  view  of  digestion, 
the  important  constituents  of  bile  are  the  bile  salts,  with  the  lecithin 
and  cholesterin  held  in  solution  by  these  salts.  The  time-relations 
of  the  secretion,  as  well  as  of  the  flow  of  bile  into  the  intestine  in 
connection  with  the  processes  of  digestion,  can  be  learnt  from  animals 
in  which  the  bile  is  conducted  to  the  outside  of  the  body  by  means 
of  a  permanent  fistula.  For  this  purpose  Pawlow  has  devised  the 
following  operation  :  In  the  dog  the  abdomen  is  opened,  and  the 
common  bile-duct  sought  as  it  passes  through  the  intestinal  wall. 
The  orifice  of  the  duct,  with  a  piece  of  the  surrounding  mucous 
membrane,  is  cut  out  of  the  wall  of  the  intestine,  and  the  aperture 
thus  made  sutured.  The  excised  portion  of  mucous  membrane,  with 
the  opening  of  the  duct,  is  then  sewn  on  to  the  surface  of  the  duodenum, 
and  the  loop  of  duodenum  at  this  point  is  stitched  into  the  abdominal 
wound.  After  healing,  the  natural  orifice  of  the  bile-duct  is  thus 
made  to  open  on  the  surface  of  the  abdomen. 

In  an  animal  treated  in  this  way  the  flow  of  bile  from  the  fistula 
is  found  to  run  parallel  to  the  pancreatic  secretion.  Although  smaller 
in  amount,  it  rises  and  falls  with  the  latter.  Thus  a  meal  of  meat 
produces  a  large  flow  of  bile,  a  meal  of  carbohydrates  only  a  small 
flow.  Moreover,  beginning  almost  immediately  after  taking  food, 
it  attains  its  maximum  with  the  pancreatic  juice  in  the  third  hour 
and  then  rapidly  dechnes. 

In  the  production  of  this  flow  of  bile  two  factors  may  be  involved  : 
(1)  the  emptying  of  the  gall-bladder  ;  (2)  an  increased  secretion  of 
the  bile.     In  order  to  determine  the  relative  importance  to  be  ascribed 


THE  BILE  805 

to  eucii.  i'tictor,  \vc  must  compare  the  results  obtained  oji  an  animal 
possessing  a  Pawlow  fistula  with  those  obtained  on  an  animal  pro- 
vided with  a  fistulous  opening  into  the  gall-bladder,  the  common  bile- 
duct  in  the  latter  having  been  hgated  to  ensure  that  the  total  secre- 
tion of  bile  passes  out  by  the  fistula.  In  such  animals  we  find,  as  we 
should  expect,  that  the  secretion  of  bile  is  a  continuous  process,  but 
that,  synchronously  with  the  great  outpouring  of  bile  into  the  intestine 
during  the  third  hour  after  a  meal,  there  is  an  increased  secretion  of 
this  fluid.  The  passage  therefore  of  the  semi-digested  food  from 
the  stomach  into  the  duodenum  causes  not  only  a  slow  contraction 
and  emptying  of  the  gall-bladder  but  also  an  increased  secretion  of 
bile  by  the  fiver.  What  is  the  mechanism  involved  in  the  production 
of  these  two  efiects  ?  The  muscular  wall  of  the  gall-bladder,  as  has 
been  shown  by  Dale,  is  under  the  control  of  nerves  derived  both 
from  the  vagus  and  from  the  sympathetic,  the  former  conveying 
motor  and  the  latter  inhibitory  impulses.  It  is  usual  to  suppose 
that  the  entry  of  acid  chyme  into  the  duodenum  provokes  reflexly 
the  contraction  of  the  gall-bladder,  but  the  exact  paths  and  steps 
in  this  reflex  act  have  not  yet  been  fully  determined.  The  increased 
secretion  of  bile,  ^\•hich  is  produced  by  the  passage  of  the  acid  chyme 
through  the  pylorus,  can  be  also  evoked  by  the  introduction  of  acid, 
such  as  04  per  cent.  HCl,  into  the  duodenum,  and  occurs  even  after 
division  of  all  connection  between  the  liver  and  the  central  nervous 
system.  vSince  the  presence  of  bile  is  necessary  for  the  full  develop- 
ment of  the  activities  of  the  pancreatic  juice,  and  its  secretion  is 
initiated  by  the  same  sort  of  stimulus,  i.e.  acid  appfied  to  the  mucous 
membrane  of  the  gut,  the  question  natm'ally  arises  whether  the 
mechanism  for  the  secretion  of  bile  may  not  be  identical  with 
that  for  the  secretion  of  pancreatic  juice.  In  order  to  decide 
this  point  we  must  make  a  temporary  bifiary  fistula  by  inserting 
a  cannula  into  the  hepatic  duct.  A  solution  of  secretin  is  then 
prepared  from  an  animal's  intestine.  In  making  this  solution  we 
must  be  careful  to  avoid  any  contamination  by  bile  salts,  which 
may  possibly  be  adherent  to  the  mucous  membrane  of  the  gut  and 
would  in  themselves,  on  injection,  evoke  an  increased  secretion  of 
bile.  It  is  therefore  better  to  extract  the  pomided  mucous  membrane 
with  boiling  absolute  alcohol,  until  this  fluid,  evaporated  into  a 
small  bulk,  shows  no  trace  of  bile  salts.  The  dried  and  powdcreil 
gut  is  then  boiled  with  dilute  acid.  On  injecting  the  soluticui  of 
secretin  so  obtained  into  the  animal's  veins,  an  increased  flow  of 
bile  is  at  once  produced.  In  one  experiment,  for  instance,  the  injec- 
tion into  the  veins  of  5  c.c.  of  a  solution  of  secretin,  prepared  in  this 
way,  increased  the  secretion  of  bile  by  the  liver  from  twenty-seven 
drops  in  fifteen  minutes  to  iifty-four  drops  in  fifteen  minutes.     The 


806  PHYSIOLOGY 

rate  of  secretion  was  therefore  doubled.  We  may  conclude  that 
the  mechanism,  by  which  the  increased  secretion  of  bile  is  pro- 
duced at  the  time  when  this  fluid  is  required  in  the  intestine,  is 
identical  with  that  for  the  secretion  of  pancreatic  juice,  and  that 
in  each  case  one  and  the  same  substance — secretin — is  formed  by 
the  action  of  the  acid  on  the  cells  of  the  mucous  membrane,  and, 
on  absorption  into  the  blood  stream,  excites  both  the  liver  and 
pancreas  to  increased  activity. 

THE  DIGESTIVE  FUNCTIONS  OF  THE  BILE 
Bile  contains  a  weak  amylolytic  ferment.  Its  uses  in  digestion 
are  dependent,  however,  not  on  the  presence  of  this  ferment,  but 
on  the  peculiar  action  of  the  bile  salts  on  the  fermentative  powers 
of  the  pancreatic  juice.  It  was  shown  long  ago  by  Williams  and 
Martin  that  the  amylolytic  power  of  pancreatic  extracts  is  doubled 
by  the  addition  of  bile  or  of  bile  salts.  Pawlow  has  stated  that  the 
same  holds  good  of  the  proteolytic  power  of  this  juice.  Most 
important,  however,  is  the  part  played  by  the  bile  in  the  digestion 
and  absorption  of  fats.  The  fat-splitting  action  of  pancreatic  juice 
is  trebled  by  the  addition  of  bile,  whether  boiled  or  miboiled.  This 
quickening  action  of  the  bile  probably  depends,  hke  its  function  in 
the  absorption  of  fats,  on  the  peculiar  physical  properties  of  the 
bile  salts,  with  those  of  the  lecithin  and  cholesterin  w^hich  they  hold 
in  solution.  Not  only  does  such  a  solution  diminish  the  surface 
tension  between  watery  and  oily  fluids,  so  promoting  the  closer 
approach  by  the  lipase  of  the  pancreatic  juice  to  the  fats  on  which 
it  is  to  act,  but  it  has  also  the  power  of  dissolving  fatty  acids  and 
soaps,  including  even  the  insoluble  calcium  and  magnesium  soaps. 
It  is  probable  that  it  aids  also  in  holding  in  solution,  and  bringing 
in  contact  with  the  fat,  the  lipase  of  the  pancreatic  juice.  It  has 
been  shown  by  Xicloux  that  the  lipase  contained  in  oily  seeds,  such 
as  those  of  the  castor  plant,  is  insoluble  in  water,  but  soluble  in  fatty 
media.  The  dried  ferment  obtained  from  the  pancreas  in  many 
cases  yields  no  lipase  to  water,  but  gives  a  strongly  lipolytic  solution 
when  extracted  with  glycerin.  The  digestive  function  of  bile  there- 
fore lies  in  its  power  of  serving  as  a  vehicle  for  the  suspension  and 
solution  of  tlie  interacting  fats,  fatty  acids,  and  fat-sjjlitting  ferjuent. 
This  vehicular  function  i)lays  an  important  part  in  the  absorption 
of  fats.  These  pass  through  the  striated  basilar  membrane  bounding 
the  intestinal  side  of  the  cipitlu'lium,  not,  as  has  been  formerly  thought, 
in  a  flne  state  of  suspension  (an  emulsion),  but  dissolved  in  the  bile 
in  the  form  of  fatty  acids  or  soaps  and  glycerin.  (Jn  the  arrival  of  these 
products  of  digestion  in  the  epithelial  cells,  a  process  of  resynthesis 
is  set  up.     Droplets  of  neutral  fat  make  their  appearance  in  the  cells, 


THE  BILE  807 

whence  they  are  passed  gradually  into  the  central  lacteal  villus  and 
so  into  the  lymphatics  of  the  mesentery  and  into  the  thoracic  duct. 
The  bile  salts  thus  released  from  their  function  as  carriers  are  absorbed 
by  the  blood  circulating  through  the  capillaries  of  the  villi,  and  carried 
by  the  portal  vein  to  the  liver.  On  arrival  they  are  once  more 
taken  up  by  the  hver-cells  and  turned  out  into  the  bile.  Owing  to  the 
fact  of  their  ready  excretion  by  the  liver-cells,  bile  salts  are  the  most 
reliable  cholalogues  with  which  we  are  acquainted.  By  this  circula- 
tion of  bile  between  liver  and  intestine  the  synthetic  work  of  the  liver 
in  the  production  of  the  bile  salts  is  reduced  to  a  minimum,  and 
it  has  only  to  replace  such  of  the  bile  salts  as  undergo  destruction 
in  the  aUmentary  canal,  under  the  influence  of  micro-organisms, 
and  are  lost  to  the  organism  by  passing  out  in  the  fseces  as  a  gummy 
amorphous  substance,  known  as  dyslysin.  Further  investigation 
is  still  wanted  as  to  the  exact  method  in  which  secretin  acts  on  the 
Uver-cells,  and  especially  as  to  whether  it  actually  excites  in  them 
the  manufacture  of  fresh  bile  salts,  or  whether  it  simply  hastens 
the  excretion  of  such  bile  salts  as  have  been  formed  by  the  spon- 
taneous activity  of  the  liver-cells  or  have  arrived  at  them  after 
absorption  from  the  alimentary  canal.  Such  questions  can  only 
be  decided  by  studying  the  action  of  secretin  on  animals  possessing  a 
permanent  biliary  fistula. 

The  effect  of  various  diets  on  the  secretion  of  bile  has  been  studied 
by  Barbera.  He  finds  that,  whereas  the  secretion  of  bile  is  greatest 
on  a  meat  diet,  it  is  somewhat  less  on  a  diet  of  fat,  and  is  insignificant 
on  a  purely  carbohydrate  diet.  That  is  to  say,  the  secretion  of  bile 
is  greatest  on  those  diets  the  digestion  of  which  is  attended  by  the 
passage  of  a  large  amomit  of  acid  chyme  or  of  oil  into  the  duodeniuu. 
Oil  is  almost  as  efficacious  as  acid  in  promoting  the  production  of 
secretin  in  the  living  duodenum,  the  production  in  this  case  being 
probably  determined  by  the  formation  of  soap  from  the  oil;,  and  the 
direct  action  of  the  soap  on  the  prosecretin  in  the  epithelial  cells  of 
the  gut. 

THE  INTESTINAL  JUICE 
For  the  development  of  one  of  its  most  important  properties, 
namely,  that  of  proteolysis,  the  pancreatic  juice  is  dependent  on  the 
co-operation  of  the  intestinal  juice  or  succus  cntericus.  Besides  this 
activating  power  on  the  pancreatic  juice,  the  intestinal  juice  has 
numerous  other  functions  to  discharge  in  tlie  digestion  of  the  food- 
stuffs. In  spite  of  the  great  similarity  which  obtains  between  the 
microscopic  structure  of  the  wall  of  the  gut  at  different  levels  from 
duodenum  to  ileocolic  valve,  functionally  there  are  many  dift'eronccs 
between  the  upper,  middle,  and  lower  portions  of  the  gut.     fc>peakiiig 


808  PHYSIOLOGY 

generally,  we  may  say  that,  whereas  the  processes  of  secretion  are 
better  marked  in  the  upper  portions  of  the  gut,  the  processes  of  absorp- 
tion predominate  in  the  lower  sections,  i.e.  in  the  ileum.  Much  of 
the  divergence  in  the  statements  which  have  been  made  with  regard 
to  the  factors  determining  secretion  and  absorption  in  the  small 
intestine  is  due  to  the  failure  to  appreciate  this  great  difference 
between  the  activity  of  the  mucous  membrane  at  various  levels. 
The  processes  of  secretion  in  the  small  intestine  may  be  studied 
by  isolating  loops  by  means  of  Hgatures,  and  determining  the  amomit 
of  secretion  formed  in  these  loops  in  the  course  of  a  few  hom's'  experi-  ■ 
ment  on  an  ansBsthetised  animal.  Better  results,  however,  may  be 
obtained  by  estabhshing  permanent  fistulse.  These  fistulas  are 
of  two  kinds.  Thiry's  original  method  of  establishing^a  fistula 
consisted  in  cutting  out  a  loop  of  intestine,  and  restoring  the  con- 
tinuity of  the  gut  by  suturing  the  two  ends  from  which  the  loop 
had  been  severed.  The  upper  end  of  the  loop  itself  is  closed  and 
the  lower  end  is  sutured  into  the  abdominal  wound.  For  some 
purposes  it  is  better  to  make  a  Thiry-Vella  fistula.  In  this  case 
the  continuity  of  the  gut  is  restored  as  in  the  simple  Thiry  fistula, 
but  both  ends  of  the  excised  loop  are  left  open  and  brought  into  the 
abdominal  wound.  In  such  a  fistula  it  is  easy  to  introduce  substances 
into  the  upper  end  and  determine  the  flow  of  juice  from  the  lower 
end,  the  constant  emptying  of  the  loop  being  provided  for  by  the 
peristaltic  contractions  of  its  muscular  coat. 

In  animals  with  intestinal  fistulse  a  number  of  different  conditions 
have  been  found  to  give  rise  to  a  flow  of  succus  entericus,  and  so 
far  no  quahtative  difference  has  been  recorded  between  the  upper 
and  lower  ends  of  the  gut.  A  condition  which  will  cause  a  free 
flow  of  juice  from  a  fistula  high  up  in  the  intestine  will  generally 
cause  a  scanty  flow  from  a  fistula  made  from  the  ileum.  In  all  cases 
it  is  found  that  a  flow  of  juice  is  produced  in  consequence  of  a  meal. 
If  a  dog  with  a  fistula,  which  has  been  starved  for  twenty-four  hours,^> " 
be  given  a  meal  of  meat,  a  flow  of  juice  may  begin  within  the  next 
ten  minutes.  The  flow  remains  very  slight  for  about  two  hours 
and  then  suddenly  increases  in  amount  during  the  third  hour,  corre- 
sponding thus  very  nearly  to  the  flow  of  pancreatic  juice  excited  by 
the  same  means.  In  this  post-prandial  secretion  of  juice  it  is  not 
probable  that  the  nervous  system  takes  any  very  large  share,  though 
its  intervention  in  the  secretion  has  not  been  excluded  by  direct 
experiment.  There  are  certain  facts  which  seem  indeed  to  speak 
for  an  action  of  the  central  nervous  system  on  the  processes  of 
intestinal  secretion,  not  in  the  direction  of  augmentation,  but  in  the 
direction  of  inhibition  of  secretion.  U'hus  it  has  been  observed,  on 
many  occasions,  that  extirpation  of  the  nerve  plexuses  oi  the  abdomen 


THE  BILE        •  809 

or  section  of  the  splanckiiic  nerves  causes  a  condition  of  diarrhoea 
which  may  last  for  two  or  three  days.  This  condition  might  be 
determined  either  by  an  increased  motor  activity  of  the  gut,  or  by 
removal  of  inhibitory  impulses  normally  arriving  at  the  intestinal 
glands.  Such  a  view  receives  support  from  an  experiment  first 
performed  by  Moreau.  The  abdomen  of  a  dog  is  opened  mider  an 
anajsthetic,  and  thi'ee  contiguous  loops  of  small  intestine  are  separated 
by  means  of  ligatures  from  the  rest  of  the  gut.  The  middle  loop 
is  then  denervated  by  destruction  of  all  the  nerve  fibres  lying  on 
its  blood-vessels,  as  they  course  through  the  mesentery,  care  being 
taken  not  to  injure  the  blood-vessels  themselves.  The  loops  are 
then  replaced  in  the  abdomen  and  the  animal  left  from  four  to  sixteen 
hours.  On  kiUing  the  animal  at  the  end  of  this  time,  it  is  often 
found  that  the  middle  loop,  i.e.  the  denervated  loop,  is  distended 
with  Huid  having  all  the  properties  of  ordinary  intestinal  juice,  whereas 
the  other  two  loops  are  empty.  A  series  of  comparative  experi- 
ments by  Mendel  and  by  Falloise  have  shown  that  the  secretion 
begins  about  four  hours  after  the  operation,  increases  for  about 
twelve  hours,  and  then  rapidly  dechnes,  so  that  at  the  end  of  two 
days  all  three  loops  will  be  found  empty.  This  has  often  been  inter- 
preted as  due  to  the  removal  of  inhibitory  impulses  passing  from 
the  central  nervous  system  to  the  local  secretory  mechanism,  and 
we  have  no  direct  evidence  which  can  be  adduced  against  such  a 
view.  It  is  possible,  however,  that  the  hyperajmia  of  the  gut,  which 
is  produced  by  the  processes  of  denervation,  may  be  sufficient  to 
accomit  for  the  increased  formation  of  intestinal  juice,  since  the 
hypersemia  wdll  tend  to  pass  off  as  the  vessels  recover  a  local  tone. 

It  is  not  possible  to  explain  the  How  of  intestinal  juice  which 
follows  a  meal  by  any  assumption  of  nervous  impulses  transmitted 
through  the  local  nerve  plexuses  of  the  gut,  since  these  have  been 
divided  in  the  making  of  the  fistula.  If  we  exclude  a  nervous  reflex 
action  by  the  long  paths,  namely,  through  the  spinal  cord  and  the 
sympathetic  or  vagus  nerves,  the  flow  which  attends  the  passage  of 
food  into  the  first  part  of  the  duodenum  must  be  excited  by  the 
formation  of  some  chemical  messenger.  As  to  the  existence  of  such 
a  chemical  messenger  or  hormone  for  the  intestinal  secretion  there 
can  be  no  doubt,  but  the  evidence  as  to  its  precise  nature  is  at  present 
conflicting.  It  is  stated  by  Pawlow  that  the  most  efl'ective  stimulus 
to  the  flow  of  succus  entericus  is  the  presence  of  pancreatic  juice 
in  the  loop  of  gut.  No  evidence  has  yet  been  brought  forward  that 
injection  of  pancreatic  juice  into  the  blood  stream  will  cause  any 
flow  of  intestinal  juice.  On  the  other  hand,  Delezenne  and  Kioujn 
have  shown  that  in  animals  provided  with  a  permanent  listula 
involving  the  duodenum  or  upper  part  of  the  jejunum,  iutravenous 


810  PHYSIOLOGY 

injection  of  secretin  always  causes  a  secretion  of  intestinal  juice.  In 
the  upper  part  of  the  gut  therefore  the  simultaneous  presence  of 
the  three  juices  necessary  for  complete  duodenal  digestion  is 
ensured  by  one  and  the  same  mechanism,  namely,  by  the  simul- 
taneous activity  of  the  secretin,  produced  in  the  intestinal  cells  by 
the  action  of  the  acid  chyme,  on  pancreas,  liver,  and  intestinal 
glands.  Recently  a  further  chemical  inechanism  for  the  arousing  of 
intestinal  secretion  has  been  described  by  Frouin.  According  to 
this  observer,  the  flow  of  juice  can  be  excited  by  intravenous  injection 
of  intestinal  juice  itself.  Since  this  juice  is  alkaline,  and  does  not 
produce  any  effect  on  the  pancreas,  it  must  be  free  from  pancreatic 
secretin.  It  would  seem  therefore  that  the  flow  of  juice  in  the 
upper  part  of  the  gut,  excited  by  the  pancreatic  secretin,  causes 
also  a  production  of  a  different  secretin  or  hormone,  which  can  be 
absorbed  from  the  Imnen  of  the  gut,  travel  by  the  bl' od  stream  to 
other  segments  of  the  small  intestine,  and  there  excite  a  secretion 
in  preparation  for  the  on-coming  food.  Further  experiments  are, 
however,  necessary  on  this  point. 

The  glands  of  the  small  intestine  can  also  be  excited  by  direct 
mechanical  stimulation  of  the  mucous  membrane.  The  easiest 
method  of  exciting  a  flow  of  intestinal  juice  from  a  permanent  fistula 
is  to  introduce  into  the  intestine  a  rubber  tube.  The  presence  of 
the  solid  object  in  the  gut  causes  a  secretion,  and  within  a  few  minutes 
drops  of  juice  can  be  obtained  from  the  free  end  of  the  tube.  The 
object  of  such  a  sensibility  to  mechanical  stimuh  is  obvious  ;  it  is 
of  the  highest  importance  that  the  onward  passage  of  any  soUd  object, 
especially  if  it  be  indigestible,  shall  be  aided  by  the  further  secretion 
of  juice  in  the  portions  of  gut  which  are  immediately  stimulated. 
This  mechanical  stimulation  probably  acts  on  the  tubular  glands 
of  the  intestine  through  the  intermediation  of  the  local  nervous 
system,  the  plexus  of  Meissner.  It  is  stated  by  Pawlow  that  a  juice 
obtained  by  mechanical  stimulation  differs  from  that  produced  by 
the  introduction  of  pancreatic  juice  into  the  loop  in  containing  httle 
or  no  enterokinase,  so  that  the  pancreatic  juice  excites  the  secretion 
of  the  substance  which  is  necessary  for  its  own  activation. 

CHARACTERS  OF  INTESTINAL  JUICE 
The  intestinal  juice  obtained  from  a  permanent  fistula  has  a 
specific  gravity  of  about  lOK).  It  is  generally  turbid  from  the  presence 
in  it  of  migrated  leucocytes  and  disintegrated  epithelial  cells.  It 
contains  about  1-5  per  cent,  total  sohds,  of  which  0-8  per  cent,  are 
inorganic  and  consist  chiefly  of  sodium  carbonate  and  sodium  chloride. 
It  is  markedly  alkaline  in  reaction,  but  loss  so  than  the  pancreatic 
juice.     The  organic  matter,  besides  a  small  amount  of  serum  albumin 


THE  BILE  811 

and  serum  globulin,  includes  a  number  of  ferments,  all  of  which  are 
adapted  to  complete  the  processes  of  digestion  of  the  food-stuffs 
commenced  in  the  stomach  and  duodenmn.  Of  these  ferments  two 
are  concerned  in  proteolysis.  Enterokinase  we  have  already  studied 
in  detail.  Possessing  no  action  itself  on  proteins,  it  is  a  necessary 
condition  for  the  development  of  the  full  proteolytic  powers  of  the 
pancreatic  juice.  In  addition  to  this  ferment  another  ferment  has 
been  described  by  Cohnheim  under  the  name  '  erepsin.'  Erepsin 
or  some  similar  ferment  is  present  in  the  fresh  pancreatic  juice  and 
in  almost  all  tissues  of  the  body.  It  is  distinguished  by  the  fact 
that,  although  it  has  no  power  of  digesting  coagulated  protein  or 
gelatin,  and  only  slowly  dissolves  caseinogen  and  fibrin,  it  has  a 
rapid  hydrolytic  effect  on  the  first  products  of  proteolysis,  converting 
albumoses  and  peptones  into  amino-  and  diamino-acids— their 
ultimate  cleavage  products. 

The  other  ferments  of  the  intestinal  juice  are  connected  with 
the  digestion  of  carbohydrates.  In  all  mammals  the  intestinal  juice 
is  found  to  contain  mvertase,  which  transforms  cane  sugar  into  glucose 
and  levulose  or  fructose,  and  maltase,  which  converts  maltose  into 
glucose.  In  young  mammals,  as  well  as  in  those  in  whom  the  milk 
diet  is  continued  throughout  Ufe,  the  intestinal  mucous  membrane 
also  contains  lactase,  i.e.  a  ferment  converting  milk  sugar  into  galac- 
tose and  glucose.  Such  a  ferment  can  be  extracted  from  the  mucous 
membrane  of  all  young  animals,  but  may  be  very  sUght  or  even 
absent  in  the  intestines  of  older  animals,  when  it  is  no  longer 
needed  for  the  ordinary  processes  of  nutrition.  By  means  of  these 
three  ferments,  coming  as  they  do  after  the  digestion  of  the 
starches  by  the  amylase  of  the  saliva  and  pancreatic  juice,  it  is 
provided  that  all  the  carbohydrate  food  of  the  animal  is  transformed 
into  a  hexose,  in  which  form  alone  carbohydrate  can  be  taken  up 
and  assimilated  by  the  cells  of  the  body.  The  seat  of  origin  of  these 
various  ferments  has  been  the  subject  of  special  investigations  by 
Falloise.  Whereas  secretin  can  be  obtained  from  the  whole  thick- 
ness of  the  mucous  membrane,  and  is  probably  therefore  contained 
in  the  form  of  prosecretin  in  the  epithehal  cells  covering  the  villi 
as  well  as  in  those  lining  the  follicles  of  Lieberkuhn,  a  superficial 
scraping  of  the  mucous  membrane,  which  removes  only  the  epithelial 
cells  covering  the  villi  with  the  adherent  mucus  and  intestinal  secre- 
tion, gives  a  much  more  active  solution  of  enterokinase  than  a  deeper 
scraping.  The  most  active  solutions  of  enterokinase  are,  however, 
to  be  obtained  from  the  iUiid  found  in  the  cavity  of  the  intestine 
after  the  injection  of  secretin.  It  seems  therefore  that  enterokinase 
is  not  i)resent  as  such  in  the  epithelial  cells,  but  is  iirst  pmduced 
in  the  process  of   secretion    and    formation    of   the  intestinal  juice. 


812  PHYSIOLOGY 

The  other  ferments,  namely,  erepsin,  maUase,  invertase,  and  lactase, 
probably  pre-exist  as  such  in  the  epithehal  cells,  especially  in  those 
hning  the  tubular  glands  of  the  gut,  since  pounded  mucous  mem- 
brane in  water  yields  a  solution  of  these  ferments  which  is  generally 
more  powerful  in  its  action  than  the  succus  entericus  itself.  So 
great  is  the  difference,  in  fact,  that  many  physiologists  have  suggested 
that  the  chief  action  of  these  ferments  occurs,  not  in  the  lumen  of 
the  gut,  but  in  the  passage  of  the  food-stufEs  through  the  epithelial 
cells  of  the  small  intestine  on  their  wav  to  the  blood-vessels- 


SECTION  VII 

FUNCTIONS  OF  THE  LARGE  INTESTINE 

GrREAT  difterences  are  found  in  the  structure  of  the  large  intestine 
of  different  animals,  differences  which  depend,  not  on  the  zoological 
position  of  the  animal,  but  entirely  on  the  nature  of  its  food.  In  the 
carnivora  the  large  intestine  is  short  and  narrow  and  possesses  little 
or  no  caecum.  In  herbivora  the  large  intestine  is  well  developed 
with  sacculated  walls,  and  the  caecum,  i.e.  that  part  of  the  large 
gut  distal  to  the  opening  of  the  ileum  into  the  colon,  is  very  large. 
Man  occupies  a  somewhat  intermediate  position  between  these  two 
classes.  The  differences  between  the  total  length  of  the  alimentary 
canal  in  various  animals  are  largely  determined  by  the  varying 
development  of  the  large  intestine.  The  relation  of  these  differences 
to  the  diet  is  seen  if  we  compare  the  length  of  the  intestine  with  the 
length  of  the  animal.  Thus  in  the  cat  the  intestine  is  three  times 
the  length  of  the  animal,  in  the  dog  from  four  to  six  times,  in  man 
from  seven  to  eight  times,  in  the  pig  fourteen  times,  and  in  the  sheep 
twenty-seven  times.  The  gxeat  development  of  the  large  intestine 
in  vegetable  feeders  is  due  to  the  fact  that  in  this  class  of  food  all 
the  nutritious  material  is  enclosed  in  cells  surrounded  by  cellulose 
walls.  In  order  that  the  food-stuffs,  e.g.  proteins,  starch,  &c.,  may 
be  dissolved  by  the  digestive  juices  and  absorbed  by  the  wall  of  the 
gut,  these  cellulose  walls  must  be  disintegrated.  In  none  of  the 
higher  vertebrates  do  we  find  any  cellulose  digesting  ferment,  cijtase, 
produced  in  the  alimentary  canal.  The  cellulose  has  therefore  to 
be  dissolved  either  by  the  agency  of  bacteria  or  by  means  of  cellulose- 
dissolving  ferments  which  may  be  present  in  the  vegetable  cells 
themselves.  Thus  in  ruminants  the  masses  of  grass  and  hay  are 
first  received  into  the  paunch,  where  they  are  kept  warm  and  moist 
with  saliva.  In  the  paunch  opportunity  is  thus  given  for  the  develop- 
ment of  huge  numbers  of  micro-organisms  which  can  dissolve  cellulose. 
From  time  to  time  portions  of  the  sodden  mass  are  returned  to  the 
mouth,  chewed,  and  then  swallowed  again  to  be  subjected  to  the 
action  of  the  proper  digestive  juices.  In  the  horse  and  rabbit  the 
chief  part  of  the  digestion  of  the  cellulose  occurs  in  the  csecum. 
Even  after  abstinence  from  food  for  some  time  the  cnocum  is  still  found 
to  contain  food  material.     In  the  csBcum,  under  the  action  of  bacteria, 

813 


814  PHYSIOLOGY 

the  cellulose  is  dissolved  and  the  cells  are  opened  up  so  as  to  allow 
their  contents  to  escape.  The  products  of  digestion  of  cellulose 
include  a  numlber  of  organic  acids,  chiefly  of  the  lower  fatty  acid 
series,  as  well  as  methane,  carbon  dioxide,  and  hydrogen.  In  the 
paunch  the  acids  accumulate  so  that  fenuentation  occurs  in  an  acid 
medium,  whereas  in  the  ctecum  the  acids  are  neutralised  by  the 
secretion  of  alkalies  and  the  reaction  remains  practically  neutral. 
The  products  of  digestion  of  cellulose,  as  well  as  the  contents  of  the 
vegetable  cells  set  free  by  the  solution  of  the  cell  walls,  are  gradually 
absorbed  by  the  walls  of  the  large  gut.  In  carnivora  the  large 
intestine  has  very  unimportant  functions  to  discharge  in  digestion 
and  absorption.  The  proteins  of  meat  are  practically  entirely 
absorbed  by  the  time  that  the  food  has  arrived  at  the  ileocolic  valve, 
and  the  same  appHes  to  fat.  In  man  the  importance  of  the  large 
intestine  will  vary  with  the  nature  of  his  food.  Under  the  con- 
ditions of  civilised  hfe  the  food  material  is  almost  entirely  absorbed 
by  the  time  that  it  reaches  the  lower  end  of  the  ileum.  If,  however, 
a  large  quantity  of  vegetable  food  be  taken,  such  as  fruit  or  green 
vegetables,  or  cereals  roughly  prepared  and  coarsely  ground,  a  con- 
siderable amount  of  material  may  reach  the  large  intestine  un- 
absorbed.  A  certain  proportion  of  this  may  undergo  absorption 
in  the  .large  intestine,  while  the  rest  will  pass  out  with  the  faeces, 
increasing  their  bulk. 

It  is  hardly  possible  to  speak  of  a  secretion  by  the  mucous  mem- 
brane of  the  large  intestine.  In  herbivora  alkaline  carbonates  are 
secreted  to  neutralise  the  acids  produced  in  the  bacterial  fermenta- 
tion of  the  food,  but  the  processes  of  absorption  and  secretion 
keeping  pace,  there  is  no  accumulation  of  the  products  of  secretion 
in  the  intestine.  A  section  of  the  mucous  membrane  shows  a  niunber 
of  simple  tubular  glands.  The  greater  nimiber  of  the  cells  lining 
these  glands  are  typical  '  goblet '  cells  and  contain  plugs  of  mucin. 
The  secretion  of  mucus  not  only  aids  the  passage  of  the  faices  along 
the  gut,  but  probably  impedes  the  propagation  of  the  bacteria 
which  are  present  in  countless  numbers  in  the  faeces.  This  may 
account  for  the  fact  that  although  bacteria  are  so  numerous  in  the 
faeces,  it  is  difficult  to  cultivate  any  large  numbers,  most  of  them 
being  dead. 

As  an  absorbing  organ  the  large  intestine  of  man  is  of  little  import- 
ance. From  observations  on  fistulae  in  man  it  has  been  calculated 
that  about  500  c.c.  of  water  pass  the  ileocohc  valve  in  the  twenty- 
four  hours.  Of  these  about  4C0  c.c.  undergo  absorption  in  the  large 
intestine.  The  absorption  of  any  of  the  food  substances  by  this 
part  of  the  gut  is  much  slower  than  that  which  takes  place  on  intro- 
duction by  the  mouth.     Feeding  by  nutrient  enemata  is  thus  always 


FUNCTIONS  OF  THE  LARGE  INTESTINE  815 

very  inadequate.  In  some  cases  after  the  introduction  of  large 
enemata  into  tlie  large  intestine  a  certain  amount  may  escape  back- 
wards into,  the  ilemn  and  may  there  undergo  absoiptio)).  The 
isolated  large  intestine  of  man  is  able  to  absorb  only  about  six  grammes 
of  dextrose  per  hour  and  about  80  c.c.  of  water.  If  egg  albumin 
or  caseinogen  solutions  be  introduced  by  the  rectmn  no  absoiption 
can  be  detected  after  several  hours.  In  observations  extending  over 
a  considerable  time  some  disappearance  has  been  observed  of  proteins 
and  emulsified  fats,  as  well  as  of  boiled  starch.  This  was  due,  how- 
ever, to  the  action  of  bacteria  on  these  substances,  and  was  probably 
of  very  little  value  for  the  nourishment  of  the  individual.  Feeding 
by  nutrient  enemata  is  thus  merely  a  method  of  slow  starvation. 
If  it  is  employed  it  should  be  limited  to  administration  of  water, 
salines,  or  solutions  of  glucose. 

The  chief  value  of  the  large  intestine  in  carnivora  and  in  civilised 
man  would  seem  to  be  as  an  excretory  organ,  since  it  plays  an  impor- 
tant part  in  the  excretion  of  lime,  magnesium,  iron,  and  phosphates. 
Lime  salts  are  excreted  partly  with  the  faeces,  partly  in  the  urine. 
The  path  taken  by  the  lime  under  different  conditions  varies  with 
the  character  of  the  other  constituents  of  the  food.  If  phosphates 
are  present  in  large  quantities  the  greater  part  of  the  lime  will  be 
excreted  by  the  large  intestine  and  escape  with  the  faeces  as  insoluble 
calcium  phosphate.  If  acids  be  administered,  such  as  hydrochloric 
acid,  the  amount  of  lime  in  the  urine  will  increase,  that  in  the  faeces 
will  diminish.  Thus  in  herbivora  normally  only  about  3  to  G  per 
cent,  of  the  lime  is  excreted  with  the  urine,  whereas  in  carnivora 
with  an  acid  urine  the  proportion  leaving  the  body  by  this  channel 
rises  to  27  per  cent.  The  excretion  of  magnesium  is  determined  bv  very 
similar  conditions.  Its  phosphates  are  somewhat  more  soluble  than 
those  of  lime.  Thus  in  man  about  50  per  cent,  of  the  magnesium  leaving 
the  body  is  contained  in  the  urine,  whereas  the  amount  of  lime 
contained  in  the  faeces  in  man  is  ten  to  twenty  times  as  much  as  that 
contained  in  the  urine.  It  must  be  remembered  that  the  whole  of 
this  difference  is  not  due  to  excretion  of  lime  into  the  gut.  since  a 
certain  proportion  of  this  substance  may  be  precipitated  as  an 
insoluble  phosphate  or  carbonate  in  the  upper  part  of  the  small 
intestine  and  pass  through  the  gut  without  undergoing  absorption. 

The  absorption  of  iron  takes  place  in  the  duodenum  and  upper 
part  of  the  jejunum.  Only  1  or  2  milligrammes  appear  in  the  urine, 
all  the  rest  being  excreted  in  the  large  gut  and  appearing  in  the 
faeces,  chiefly  as  sulphide  of  iron. 

Of  the  acid  radicals  phosphates  may  pass  out  either  with  the  urine  or 
with  the  faeces,  the  exact  path  taken  being  determined  by  the  relative 
amount  of  calcium  and  iiikalinc  metals  present  in  the  food.     If  there 


816  PHYSIOLOGY 

is  an  excess  of  calcium  most  of  the  phosphates  will  leave  with  the 
faeces. 

The  large  intestine  is  the  main  channel  of  excretion  for  certain 
substances  which  cannot  be  regarded  as  normal  constituents  of  the 
food,  e.q.  the  heavy  metals,  such  as  bismuth  and  mercury.  If 
bismuth  be  administered  subcutaneously  the  faeces  will  be  found  to 
contain  this  substance,  and  the  wall  of  the  large  intestine  will  be 
stained  black  from  a  deposit  of  sulphide  of  bismuth.  This  deposit 
stops  short  at  tlie  ileocolic  valve.  The  excretion  of  mercury  by  the 
wall  of  the  large  intestine  may  account  for  the  frequent  presence  of 
ulceration  of  this  part  of  the  gut  in  cases  of  poisoning  by  mercury. 


SECTION  VIII 

MOVEMENTS  OF  THE  INTESTINES 

The  movements  of  the  intestines  can  be  investiiiated  either  by 
observation  of  the  exposed  gut,  or  by  the  shadow  method  introduced 
by  Cannon,  in  which  the  nature  of  the  movements  is  judged  from 
the  shadows  of  food  containing  bismuth  which  are  thrown  on  a 
sensitive  screen  by  means  of  the  Rontgen  rays.  These  movements 
have  been  the  subject  of  experimental  investigation  for  many  years, 
but  with  varpng  results.  The  great  discrepancy  which  obtained 
between  the  statements  of  earlier  observers  is  due  to  the  fact  that 
they  failed  to  exclude  the  many  disturbing  impulses  which  can  play 
on  any  segment  of  the  gut,  either  reflexly  through  the  central  nervous 
system,  or  from  other  parts  of  the  ahmentary  canal  itself  through 
the  local  nervous  system.  In  order  to  observe  the  normal  move- 
ments of  the  gut,  it  is  necessary  to  exclude  the  disturbing  influences 
due  to  reflexes  through  the  central  nervous  system  either  by  extir- 
pation of  the  whole  of  the  nerve  plexuses  in  the  abdomen,  or  by 
division  of  the  splanchnic  nerves,  or  by  destruction  of  the  lower  part 
of  the  spinal  cord  from  about  the  middle  dorsal  region.  If  the 
abdomen  of  an  animal  which  has  been  treated  in  this  way  be  opened 
in  a  bath  of  warm  normal  salt  solution,  so  as  to  exclude  the  disturbing 
influence  of  drying  and  cooling  of  the  gut,  the  small  intestine  will  be 
seen  to  present  two  kinds  of  movements.  In  the  first  place,  all 
the  coils  of  gut  undergo  swaying  movements  from  side  to  side — 
the  so-called  pendular  movements.  Careful  observation  of  anv  coil 
will  show  that  these  movements  are  attended  with  slight  waves  of 
contraction  passing  rapidly  over  the  surface.  If  a  rubber  balloon, 
filled  with  air  and  connected  with  a  tambour,  be  inserted  into  any 
part  of  the  gut,  it  will  reveal  the  existence  of  rhj-thmic  contractions 
of  the  circular  muscle  repeated  from  twelve  to  thirteen  times  per 
minute.  By  means  of  a  special  piece  of  apparatus  (the  '  entero- 
graph  ■)  it  is  possible  without  opening  the  gut  to  record  the  move- 
ments of  either  circular  or  longitudinal  muscular  coats  ;  and  it  is 
then  found  that  both  coats  present  rhythmic  contractions  at  the  same 
rate,  the  two  coats  at  any  point  contracting  synchronously.  When 
the  contractions  are  recorded  by  means  of  a  balloon,  the  constriction 
which  accompanies  each  contraction  is  seen  to  be  most  marked  at 

817  52 


818  PHYSIOLOGY 

the  middle  of  the  balloon.,  i.e.  at  the  point  of  greatest  tension.,  and 
the  amplitude  of  the  contractions  is  augmented  by  increasing  the 
tension  on  the  walls  of  the  gut.  These  movements  are  unaffected 
bv  the  direct  application  of  drugs  such  as  nicotine  or  cocaine,  which 
we  might  expect  to  paralyse  any  local  nervous  structures  in  the 
wall  of  the  gut.  Bayliss  and  Starling  concluded  that  these  rhythmic 
contractions  were  myogenic.*  that  they  were  propagated  from  muscle 
fibre  to  muscle  fibre,  and  that  they  coursed  down  the  gut  at  the  rate 
of  about  5  cm.  per  second.  Since,  however,  they  may  apparently  arise 
at  any  portion  of  the  gut  which  is  subject  to  any  special  tension,  it 
is  not  easy  to  be  certain  that  a  contraction  recorded  at  any  point  is 
really  propagated  from  a  point  two  or  three  inches  higher  up.  These 
contractions  must  cause  a  thorough  mixing  of  the  contents  of  the  gut 
with  the  digestive  fluids.  On  examining  under  the  Rontgen  rays  the 
intestines  of  a  cat  which  has  taken  a  large  meal  of  bread  and  milk 
mixed  with  bismuth  some  hours  previously,  a  length  of  gut  may  be 
seen  in  which  the  food  contents  form  a  continuous  column.  Suddenly 
movements  occur  in  this  column,  which  is  split  into  a  number  of  equal 
segments.  Within  a  few  seconds  each  of  these  segments  is  halved,  the 
corresponding  halves  of  adjacent  segments  uniting.  Again  contractions 
recur  in  the  original  positions,  dividing  the  newly  formed  segments 
of  contents  and  re-forming  the  segments  in  the  same  position  as 
they  had  at  first  (Fig.  341).  If  the  contraction  is  a  continuous 
propagated  wave,  it  is  evidently  reinforced  at  regular  intervals  down 
the  gut,  so  as  to  divide  the  colmnn  of  food  into  a  number  of  spherical 
or  oval  segments.  The  points  of  greatest  tension  immediately  become 
the  points  which  are  midway  between  the  spots  where  the  first 
contractions  were  most  pronounced.  The  second  contractions 
therefore  start  at  these  points  of  greatest  tension,  and  divide  the 
first  formed  segments  into  two  parts,  which  join  with  the  corresponding 
halves  of  the  neighbouring  segments.  In  this  way  every  particle  of 
food  is  brought  successively  into  mtimate  contact  with  the  intestinal 
wall.  These  movements  have  not  a  translatory  effect,  and  a  column 
of  food  may  remain  at  the  same  level  in  the  gut  for  a  considerable 
time. 

The  onward  progress  of  the  food  is  caused  by  a  true  peristaltic 

*  Magnus  has  sho^^'n  that  it  is  possible  to  piill  ofF  strips  of  the  longitudinal 
(outer)  coat  of  muscle  fibres  from  the  small  intestine.  Such  strips,  if  they 
contain  Auerbach's  plexus,  will  contract  rhythmically  if  kept  in  warm  oxygenated 
Ringer's  fluid.  If,  however,  the  plexus  has  been  left  behind  in  stripping  off 
the  muscle,  no  rhythmic  contractions  are  to  be  observed,  although  contraction 
can  still  be  excited  by  artificial  stiraiilation.  Magnus  concludes  that  even  the 
rhythmic  '  pendular  '  contractions  depend  for  their  occurrence  on  the  integrity 
of  the  connection  between  local  ganglionic  centres  and  muscle  fibres,  and  carmot 
therefore   be   strictly  regarded   as   myogenic. 


MOVEMENTS  OF  THE  INTESTINES 


819 


contraction,  i.e.  one  which  involves  contraction  of  the  gut  above 
the  food  mass  and  relaxation  of  the  gut  below.  If  a  balloon  be 
inserted  in  the  lumen  of  the  exposed  gut,  it  will  be  found  that  pinching 


B 


Fu;.  .'Wl.  JJiagraiu  of  the  '  aogiucntatiou  '  (pendular)  movements  of  the  intes- 
tines  as  observed  by  the  Rontgen  rays,  after  administration  of  bif^muth. 
(Cannon.) 

1.  A  continuoxis  column,  intestinal  movements  being  absent.  2.  The 
column  broken  up  into  segments.  3.  Five  seconds  later,  each  segment 
divided  into  two,  tlie  halves  joining  the  corresponding  halves  of  adjacent 
segments.     4.  Condition  (2)  repeated  five  seconds  later. 


the  gut  above  the  balloon  causes  an  immediate  relaxation  of  the 
muscular  wall  in  the  neighbourhood  of  the  balloon.  This  inhibitory 
influence  of  the  local  stimulus  may  extend  as  much  as  two  feet  down 
the   intestine   towards   the   ileocaecal   valve.      On   the    other   hand, 


Fro.  342.     Intestinal  contractions  (balloon  method).     In  this  dog  all  the  abdo- 
minal ganglia  had  been  excised,  and  both  vagi  cut.     Showing  propagated 
effects  of  mechanical  stimulation,  above  and  below  the  balloon. 
(1)  pinch  above,  (2)  pinch  below,  (3)  pinch  below  balloon. 

j (inching  the  gut  half  an  inch  below  the  situation  of  the  balloon  causes 
a  strong  continued  contraction  to  occur  at  the  balloon  itself  (Fig.  342). 
Stimulation  at  any  portion  of  the  gut  causes  contraction  above 
th(^  |)()int  of  stimidus  and  relaxation  below  the  point  of  stinnilus 
(the  '  law  of  the  intestines ').  The  same  effect  is  produced  by 
introduction   of   a   bolus  of  food,  especially  if   it   be  large  or  have 


820  PHYSIOLOGY 

a  direct  irritating  effect  on  the  wall  of  the  gut  (Fig.  343).  In  this  case 
the  contraction  above  and  the  inhibition  below  cause  an  onward 
movement  of  the  bolus,  which  travels  slowly  down  the  whole  length 
of  the  gut  until  it  passes  through  the  ileocaecal  opening  into  the 
large  intestine.  The  peristaltic  contraction  involves  the  co-operation 
of  a  nervous  system.  Whereas  in  the  oesophagus  it  is  the  central 
nervous  system  which  is  involved,  the  peristaltic  contractions  in 
the  small  intestine  occur  after  severance  of  all  connection  with  the 
brain  and  spinal  cord.  On  the  other  hand,  they  are  absolutely  abolished 
by  painting  the  intestine  with  nicotine  or  with  cocaine.  They  must 
therefore  be  ascribed  to  the  local  nervous  system  contained  in 
Auerbach's  plexus,  which  we  can  regard  as  a  lowly  organised  nervous 


Fig.  343.  Passage  of  bolus.  Contractions  of  longitudinal  coat  (enterograph). 
The  bolus  (of  soap  and  cotton- wool)  was  inserted  into  the  intestine  four 
inches  above  the  recorded  spot  at  A.  The  figures  below  the  tracing  indicate 
the  distance  of  the  middle  of  the  bolus  from  the  recording  levers  As  the  bolus 
arrived  two  inches  above  the  levers  there  is  cessation  of  the  rhythmic  contrac- 
tions and  inhibition  of  the  tone  of  the  muscle.  This  is  followed,  as  the  bolus  is 
forced  past,  by  a  strong  contraction  in  the  rear  of  the|bo]us. 

system  with  practically  one  reaction,  namely,  that  formulated  above 
as  the  '  law  of  the  intestines.'  An  anti-peristalsis  is  never  observed 
in  the  small  intestine.  Mall  has  shown  that,  if  a  short  length  of  gut 
be  cut  out  and  reinserted  in  the  opposite  direction,  a  species  of 
partial  obstruction  results,  in  consequence  of  the  fact  that  the  peri- 
staltic waves,  started  above  the  point  of  operation,  cannot  travel 
downwards  over  the  reversed  length  of  gut.  The  intestine  above 
this  point  therefore  becomes  dilated.  If,  however,  the  reactions 
of  the  local  nervous  system  be  paralysed  or  inhibited,  a  reflux  of 
intestinal  contents  is  quite  possible,  since  the  contractions  excited 
at  any  spot  by  local  stimulation  of  the  muscle  have  the  eSect  of 
driving  the  food  either  upwards  or  downwards  ;  the  direction  of 
movement  of  the  food  will  be  that  of  least  resistance. 

The  movements  of  the  small  intestine  are  also  subject  to  the 
central  nervous  system.  Stimulation  of  the  vagus  has  the  effect  of 
producing  an  initial  inhibition  of  the  whole  small  intestine,  followed 


MOVEMENTS  OF  THE  INTESTINES 


821 


by  increased  irritability  and  increased  contractions  (Fig.  344).  On  the 
other  hand,  stimulation  of  the  splanchnic  nerves  causes  complete 
relaxation  of  both  coats  of  the  small  gut  (Fig.  345).  It  seems  that  the 
splanchnics  normally  exercise  a  tonic   inhibitory  influence   on  the 


Fig.  344.     Effect  of  stimuhitiuu  of  right  vagus  on  intestmal  contractions. 


l-'XG.  34.3.     Excitation  of  both  .splauclinic  nciVL-s 
Intofctinc  ictumcd  to  abdomen. 


Balloon  nic'tliod. 


intestinal  movements,  which  can  be  increased  by  all  manner  of  peri- 
pheral stimuli.  On  this  account  it  is  often  impossible  to  obtain  any 
movements  in  the  exposed  intestine  so  long  as  these  remain  in  connec- 
tion with  the  central  nervous  system  through  the  .splanchnic  nerves. 
The  relaxed  condition  of  the  gut  which  obtains  in  many  abdominal 
affections  is  probably  also  reflex  in  origin,  and  is  due  to  reflex  inhibition 
through  the  splanchnic  nerves. 

As  a  result  of  the  two  sets  of   movements  described  above,  the 


822  PHYSIOLOGY 

food  is  tliorou,i;lily  mixed  with  the  dij-estive  juices,  and  tlie  greater 
part  of  the  products  of  digestion  are  brought  into  contact  with  the 
intestinal  wall  and  absorbed.  What  is  left — a  proportion  varying 
in  different  animals  according  to  the  nature  of  the  food — is  passed 
on  by  occasional  peristaltic  contractions  through  the  lower  end  of 
the  ileum  into  the  colon,  or  large  intestine.  The  lowest  two  centi- 
metres of  the  ileum  present  a  distinct  thickening  of  the  circular 
muscular  coat,  forming  the  ileocolic  sphincter.  This  sphincter  relaxes 
in  front  of  a  peristaltic  wave  and  so  allows  the  passage  of  food  into 
the  colon.  On  the  other  hand,  it  contracts  as  a  rule  against  any 
regurgitation  w^hich  might  be  caused  by  contractions  in  the  colon. 
Although  thus  falling  into  line  with  the  rest  of  the  muscular  coat, 
as  concerns  its  reaction  to  stimuli  arising  in  the  gut  above  or  below^ 
it  presents  a  marked  contrast  to  the  rest  of  the  gut  in  its  relation 
to  the  central  nervous  system.  It  is  unaffected  by  stimulation 
of  the  vagus.  )Stimulation  of  the  splanchnic,  however,  which  causes 
complete  relaxation  of  the  lower  part  of  the  ileum  with  the  rest  of 
the  small  intestine,  produces  a  strong  contraction  of  the  muscle- 
fibres  forming  the  ileocolic  sphincter  (ElHott). 

MOVEMENTS  OF  THE  LARGE  INTESTINE 
By  means  of  the  occasional  peristaltic  contractions,  accompanied 
by  relaxation  of  the  ileocohc  sphincter,  the  contents  of  the  small 
intestine  are  gradually  transferred  into  the  large.  In  man  these 
contents  are  considerable  in  bulk,  are  semi-fluid,  and  probably  fill 
the  ascending  as  w^ell  as  the  transverse  colon. 

The  large  intestine  is  supplied  wdth  nerves  from  the  central  nervous 
system.  These  run  partly  in  the  sympathetic  system  along  the 
colonic  and  inferior  mesenteric  nerves,  partly  in  the  pelvic  visceral 
nerves  or  nervi  erigentes,  which  come  off  from  the  sacral  cord  and 
pass  direct  to  the  pelvic  viscera.  In  addition  it  possesses  a  local 
nervous  system,  presenting  the  same  structure  as  that  found  in  the 
small  intestine.  The  movements  of  the  large  intestine  differ  con- 
siderably in  various  animals,  as  has  been  shown  by  Elliott,  according 
to  the  nature  of  the  food  and  the  part  played  by  this  portion  of  the 
gut  in  the  processes  of  absorption.  In  the  dog  the  process  of  absorp- 
tion is  almost  complete  at  the  ileocolic  valve,  whereas  in  the  herbi- 
vora  a  very  large  part  of  the  processes  of  digestion  and  absorption 
occurs  in  the  colon  and  caecum.  Man  takes  an  intermediate  position 
as  regards  his  large  intestine  between  these  two  groups  of  animals. 
Elliott  and  Barclay  Smith  divide  the  large  intestine  into  four  parts, 
according  to  their  functions,  viz.  the  csBCum,  and  the  proximal, 
intermediate,  and  distal  portions  of  the  colon.  Of  these  the  dog 
possesses  practically  only  the  distal  colon.    We  may  take  Elliott's 


MOVEMENTS  OF  THE  INTESTINES  823 

account  of  the  movements  as  they  probably  occur  in  man.  Tliey 
airrce  very  closely  with  those  observed  by  Cannon  under  Jiormal 
circumstances  in  the  cat  by  means  of  the  Kojitgen  rays.  The  food 
as  it  passes  from  the  ileum  fii-st  fills  up  the  proximal  colon.  Tlie 
effect  of  this  distension  is  to  cause  a  contraction  of  the  muscular 
wall  at  the  junction  between  the  ascending  and  transverse  colon. 
This  contraction  travels  slowly  over  the  tube  in  a  backward  direction 
towards  the  caocum,  and  is  quickly  succeeded  by  another,  so  that 
the  colon  may  present  at  the  same  time  several  of  these  advancing 
waves.  These  waves  are  spoken  of  as  anti-peristaltic  ;  but  as  they 
do  not  involve  also  an  advancing  wave  of  inhibition,  they  must  not 
be  regarded  as  representing  the  exact  antithesis  of  a  peristaltic  wave, 
as  we  have  defined  it.  The  effect  of  these  waves  is  to  force  the  food 
up  into  the  ca)cum,  regurgitation .  into  the  ileum  being  prevented 
partly  by  the  obHquity  of  the  opening,  partly  by  the  tonic  contraction 
of  the  ileocolic  sphincter.  As  the  whole  of  the  contents  cannot 
escape  into  the  caecum,  a  certain  portion  will  sUp  back  in  the  axis 
of  the  tube,  so  that  these  movements  have  the  same  effect  as  the 
similar  contractions  in  the  pyloric  end  of  the  stomach,  causing  a 
thorough  churning  up  of  the  contents  and  its  close  contact  with 
the  intestinal  wall.  The  movements  are  rendered  still  more  effective 
by  the  sacculation  of  the  walls  of  this  part  of  the  large  intestine. 
The  distension  of  the  caecum  caused  by  this  anti-peristalsis  excites 
occasionally  a  true  co-ordinated  peristaltic  wave,  which,  starting 
in  the  caecum,  drives  the  food  down  the  intestine  into  the  transverse 
part.  These  waves  die  away  before  they  reach  the  end  of  the  colon, 
and  the  food  is  driven  back  again  by  waves  of  anti-peristalsis. 
Occasionally  more  food  escapes  through  the  ileocohc  sphincter  from 
the  ileum,  so  that  the  whole  ascending  and  transverse  colon  may  be 
fiUed  with  the  mass  undergoing  a  constant  kneading  and  mixing 
process.  The  result  of  this  process  is  the  absorption  of  the  greater 
part  of  the  water  of  the  intestinal  contents,  as  well  as  of  any  nutrient 
material,  and  the  drier  part  of  the  intestinal  mass  collects  towards 
the  splenic  flexure,  where  it  may  be  separated  by  transverse  waves 
of  constriction  from  the  more  fluid  parts  which  are  being  driven  to 
and  fro  in  the  proximal  and  intermediate  portions.  By  means  of 
occasional  peristaltic  waves  these  hard  masses  are  driven  into  the 
distal  part  of  the  colon.  The  distal  colon  must  be  regarded  as  a 
place  for  the  storage  of  the  faeces  and  as  the  organ  of  defax-ation. 
In  the  transverse  colon,  in  the  descending  and  ileo-colon,  the  anti- 
peristaltic movements  and  consequent  churning  of  the  contents 
are  probably  slight.  These  therefore  represent  the  intermediate 
colon,  with  propulsive  peristalsis  as  its  chief  activity.  The  descend- 
ing colon  is  never  distended,  and  Elliott  therefore  regarded  it  as  a 


824  PHYSIOLOGY 

transferring  segment  of  exaggerated  irritability.  The  storage  of  the 
waste  matter  takes  place  chiefly  in  the  sigmoid  flexure.  This  with  the 
rectum  represents  the  distal  portion  of  the  colon.  The  distinguishing 
feature  of  the  distal  colon  is  its  complete  subordination  to  the  spinal 
centres.  It  probably  remams  inactive  until  an  increasing  distension 
excites  reflexly  through  the  pelvic  visceral  nerves  a  complete  evacua- 
tion of  this  portion  of  the  gut.  Stimulation  of  these  nerves  in  an 
animal,  such  as  the  cat,  produces  a  rapid  shortening  of  the  distal 
part  of  the  colon,  due  to  contraction  of  the  recto- coccygeus  and  longi- 


FiG.  346.  Skiagram  to  show  normal  position  of  colon  in  man,  and  the 
position  attamed  by  its  contents  at  different  jjcriods  after  a  meal  contain- 
ing bismuth.  The  bismuth  meal  was  taken  at  8  a.m.  The  times  of 
arrival  at  different  levels  are  marked  on  the  colon.     (Hertz.) 

tudinal  fibres  of  the  gut,  followed  after  some  seconds  by  a  contraction 
of  the  circular  coat.  This  originates  at  the  lower  limit  of  the  area 
of  anti-peristalsis,  i.e.  probably  at  the  upper  end  of  the  sigmoid 
flexure,  and,  spreading  rapidly  downwards,  empties  the  whole  of  this 
segment  of  the  gut.  In  man  the  emptying  of  the  rectum  itself  is 
of  course  largely  assisted  by  the  contractions  of  the  voluntary 
muscles  of  the  abdominal  walls  and  pelvic  floor. 

The  last  section  of  the  rectum  is  emptied  at  the  close  of  the  act 
by  a  forcible  contraction  of  the  levator  ani  and  the  other  perinaeal 
muscles,  and  this  contraction  also  serves  to  restore  the  everted  mucous 
membrane. 

The  carrying  out  of  this  reflex  act  is  dependent  on  the  integrity 
of  a  certain  part  of  the  lumbar  spinal  cord.  If  this  '  centre  '  be 
destroyed,  the  tonic  contraction  of  the  sphincter  muscles  disappears. 


MOVEMENTS  OF  THE  INTESTINES  825 

This  centre  may  be  either  excited  to  increased  action,  or  be  inhibited 
by  peripheral  stimulation  of  various  nerves,  or  by  emotion,  such  as 
fear.  Application  of  warmth  to  the  region  of  the  anus  causes  reflex 
relaxation  of  the  sphincter  ;  application  of  cold  increases  its  tonic 
contraction. 

In  man,  as  Hertz  has  shown  by  the  skiagraphic  method,  the 
pelvic  colon  becomes  filled  with  fajces  from  below  upwards,  the 
rectum  remaining  empty  till  just  before  defsecation.  In  individuals 
wliose  bowels  are  opened  regularly  every  morning  after  breakfast 
the  entry  of  fa3ces  into  the  rectum  gives  rise  to  a  sensation  of  fulness 
and  acts  as  the  call  to  defsecation.  If  no  response  be  made,  the 
desire  to  defsecate  passes  away,  since  the  rectum  relaxes  and  the 
faecal  mass  no  longer  exercises  pressure  on  its  wall.  Hertz  has 
shown  that  the  minimal  pressure  required  to  produce  the  call  to 
defsecate  varies  from  30  to  40  mm.  Hg,  according  to  the  length  of  the 
gut  which  is  the  seat  of  distension. 


SECTION  IX 
THE  ABSORPTION  OF  THE  FOOD-STUFFS 

THE   ABSORPTION   OF   WATER    AND   SALTS 

The  intake  of  water,  and  probably  of  salts,  by  the  alimentary 
canal,  in  accordance  with  the  requirements  of  the  organism  as  a 
whole,  seems  to  be  regulated  almost  entirely  by  the  central  nervous 
system,  the  higher  parts  of  this  system,  viz.  those  concerned  with 
appetite,  being  particularly  involved  in  the  process.  Thus  in  man 
any  large  loss  of  fluid  to  the  body,  as  by  sweating,  diarrhoea,  haemor- 
rhage, gives  rise  to  an  intense  thirst  that  has  its  natural  reaction 
in  increased  intake  of  water  by  the  mouth.  On  the  other  hand, 
the  property  possessed  by  the  alimentary  canal  of  absorbing  water 
and  weak  saline  fluids  contained  in  its  interior  is  very  little  influenced 
by  the  state  of  depletion,  or  otherwise,  of  the  water  depots  of  the 
body.  It  is  practically  impossible,  however  large  the  quantities  of 
fluid  ingested,  to  evoke  the  production  of  fluid  motions,  the  greater 
part  of  the  ingested  fluid  being  absorbed  on  its  way  through  the 
aUmentary  canal.  Thus  a  man  may  keep  himself  in  perfect  health 
and  maintain  the  water  content  of  his  body  constant  whether  he  take 
one  litre  or  six  litres  of  water  daily.  The  whole  process  of  regulation, 
apart  from  that  determined  by  appetite,  appears  to  be  carried  out  at 
the  other  end  of  the  cycle,  viz.  by  the  kidneys.  As  concerns  absorp- 
tion of  water  there  is  no  chemical  solidarity  between  the  alimentary 
surface  and  the  rest  of  the  body.  Whenever  water  is  presented  to 
the  surface  it  is  absorbed  and  passes  into  the  circulation. 

The  absorption  of  water  in  the  stomach  may  be  regarded  as  nil. 
Although  from  this  viscus  alcohol,  and  possibly  peptone  and  sugar, 
may  be  absorbed  to  a  slight  extent,  water  or  saline  fluids  intro- 
duced into  it  are  passed  through  the  pylorus  either  without  change 
or  increased  by  the  secretion  of  fluid  from  the  gastric  glands.  In 
no  case  is  there  a  diminution  of  fluid  in  the  stomach. 

The  chief  absorption  of  water  occurs  in  the  small  intestine.  It 
is  on  this  account  that  the  salient  features  of  cases  of  dilatation  of 
the  stomach  with  «teiipsis,  absolute  or  relative,  of  the  pyloric  orifice 
can  be  nearly  all  referred  to  the  starvation  of  the  body  in  water, 
and  can  be  often  relieved  by  the  administration  of  water  either  sub- 
cutaneously  or  by  the  rectum,  i.e.  by  the  channels  through  which 

82fi 


THE  ABSORPTION  OF  THE  FOOD-STUFFS 


s--*" 


absori)ti(jn  is  still  possible.  Tin-  introduction  of  water  into  the 
stomach  simply  increases  the  dilatation,  but  does  not  relieve  the 
intense  thirst  of  the  patiejit.  Water  that  has  been  swallowed  to 
quench  thirst  has  first  to  be  passed  from  the  stomach  into  the  small 
intestine  before  it  can  be  absorbed  and  relieve  the  needs  of  the  tissues. 
The  intestinal  contents  at  the  ileocaecal  valve  contain  relatively 
nearly  as  much  water  as  they  do  at  the  upper  part  of  the  jejunum. 
Their  absolute  bulk  is,  however,  much  smaller,  so  that  only  a  small 
proportion  of  the  water  that  has  been  taken  in  by  the  mouth  remains 
to  be  absorbed  in  the  large  gut — an  amount  probably  nuich    less 


Epithelium  of 

villus 


Central  lacteal 


Lieberkuhn's 

follicle 

>rucosa 
Muscularis  muc. 

Submucosa 
Lymphatic  plexus 
Circular  muscle 

Lymphatic  plexus 
Longitudinal  muse. 

Fig.  347.  Diagraiimiaue  ><•( mm  uiiuiiyxi  uali  ui  ^luall  intestine  to  show 
vascular  and  lymphatic  arrangements  of  mucous  membrane.  (From 
BoHM  and  Davidoff  after  Mall.) 

than  that  which  has  been  added  to  the  contents  of  the  small  intestine 
in  the  form  of  secretion  by  the  stomach,  liver,  pancreas,  and  intestinal 
tubules. 

The  main  problem  before  us  is  therefore  the  mechanism  of  absorp- 
tion of  water  and  saline  fluids  by  the  villi  of  the  small  intestine. 
By  means  of  these  structures  the  absorbing  surface  of  the  intestine 
is  largely  increased.  It  has  been  calculated  that  each  square  milli- 
metre of  intestine  represents  an  absorbing  surface  of  3  to  12  mm.^ 
Each  villus  (Fig.  347)  consists  of  a  framework  of  reticular  tissue  con- 
taining many  leucocytes  in  its  meshes,  separated  from  the  lumen  of 
the  gut  by  a  continuous  layer  of  columnar  epithelial  cells.  These  cells 
rest  on  an  incomplete  basement  membrane  and  present  on  the  side 
turned  towards  the  lumen  of  the  gut  a  striated  basilar  border.  The 
villus  ofiEers  two  channels  by  means  of  which  material,  which  has 
passed  through  the  epithelium,   may    be   carried   into    the    general 


828  PHYSIOLOGY 

circulation.  In  the  centre  of  the  villus  is  the  central  lacteal,  a  club- 
shaped  vessel  bounded  by  a  complete  layer  of  delicate  endothelial 
cells.  This  leads  into  a  plexus  of  lymphatics  placed  superficially 
to  the  muscularis  mucosae.  From  the  superficial  plexus  communi- 
cating branches  pass  vertically  to  a  corresponding  plexus  lying  in 
the  submucosa.  The  central  lacteal  and  the  superficial  plexus  are 
free  from  valves,  which,  however,  are  present  in  abundance  in  the 
deeper  plexus,  so  that  fluid  can  pass  easily  from  the  lacteal  to  the 
deeper  plexus,  but  not  in  the  reverse  direction.  From  the  muscularis 
mucosce  unstriated  muscle  fibres  pass  up  through  the  villus  to  be 
attached  partly  to  the  outer  surface  of  the  central  lacteal,  partly 
by  expanded  extremities  to  the  basement  membrane  covering  the 
surface  of  the  villus.  Contraction  of  these  muscle  fibres  will  tend 
to  empty  the  central  lacteal  into  the  deep  plexus  of  lymphatics  and 
may  also  cause  an  expulsion  of  the  contents  of  the  spaces  of  the 
retiform  tissue  of  the  villus  into  the  central  lacteal.  The  alimentary 
canal  represents  one  of  the  few  localities  where  a  formation  of  lymph 
is  constantly  proceeding,  even  in  a  condition  of  complete  rest.  On 
placing  a  cannula  in  the  thoracic  duct  of  a  dog  an  outflow  of  lymph 
is  obtained  which  may  vary  in  different  animals  between  1  c.c.  and 
10  c.c.  in  the  ten  minutes.  The  greater  part  of  this  lymph  is  derived 
from  the  alimentary  canal,  so  that  any  of  the  intestinal  contents 
which  have  made  their  way  into  the  spaces  of  the  villus  might  be 
entrained  in  this  lymph  current  and  carried  away  with  it  into  the 
thoracic  duct  and  so  into  the  general  blood  system. 

The  other  possible  channel  of  absorption  is  by  the  capillary  blood- 
vessels of  the  villus.  Each  villus  is  supplied  with  blood  from  one 
or  two  arterioles  which  break  up  into  a  rich  plexus  of  capillaries 
lying  close  under  the  basement  membrane  of  the  villus.  The  return 
blood  is  collected  into  one  or  two  veins,  which  join  the  radicles  of 
the  portal  vein  in  the  submucosa  and  in  the  mesentery.  In  these 
capillaries  the  blood  is  circulating  rapidly,  so  that  a  considerable 
amount  of  material  may  pass  into  them  from  the  spaces  of  the  villus 
within,  say,  one  hour  without  altering  appreciably  the  percentage 
composition  of  the  blood.  On  the  other  hand,  it  must  be  remem- 
bered that  the  blood  in  these  vessels  is  at  a  high  pressure,  probably 
not  less  than  30  mm.  Hg.,  so  that  any  absorption  into  the  blood 
stream  must  occur  against  this  pressure.  It  is  probable  therefore 
that  in  explaining  any  absorption  by  the  blood-vessels  we  shall  have 
to  place  out  of  court  any  possibility  of  the  passage  occurring  in  con- 
sequence of  hydrostatic  differences  of  pressure,  i.e.  by  a  process  of 
filtration. 

When  salt  solutions  are  introduced  into  the  small  intestine  they 
are  rapidly  absorbed  without  the  production  of  any  corresponding 


THE  ABSORPTION  OF  THE  FOOD-STUFFS  829 

increase  in  the  rate  of  lymph  flow  from  the  thoracic  duct.  On  the 
other  hand,  the  absorption  of  large  amounts  of  fluid  may  cause 
an  actual  diminution  of  the  solids  of  the  plasma,  so  that  we  are 
justified  in  regarding  the  capillary  network  of  blood-vessels  at  the 
surface  of  the  villi  as  solely  responsible  for  the  absorption. 

What  are  the  forces  which  cause  this  transference  of  fluid  and 
dissolved  substances  from  one  side  to  the  other  of  the  membrane, 
composed  of  epithelial  cells  plus  capillary  endothelium  ?  Like  other 
cells,  those  of  the  intestinal  epithelium  are  probably  bounded  on  their 
free  surface  by  a  '  lipoid  '  membrane,  i.e.  one  containing  some  complex 
of  lecithin  and  cholesterin  and  permeable  only  by  such  substances  as 
are  soluble  in  lipoids.  On  the  other  hand,  the  cement  substance  between 
the  cells  may  be  of  a  different  character  and  possibly  permeable  to 
water-soluble  substances.  The  question  has  been  propounded  whether 
the  greater  part  of  the  substances  which  enter  the  blood  serum  from 
the  gut  pass  between  the  cells  or  through  the  cells.  Water  could,  of 
course,  pass  in  either  way.  Most  of  the  inorganic  salts,  such  as  sodium 
chloride,  as  well  as  the  very  important  constituents  of  the  food,  the 
sugars,  are  insoluble  in  lipoids,  and  would  have  to  pass  between  the 
cells.  When  the  question  is  investigated  by  the  use  of  dyestuffs,  soluble 
or  insoluble  in  lipoids,  it  is  found  that  the  lipoid-soluble  dyestuffs,  such 
as  neutral  red  or  toluidin  blue,  pass  into  the  cells,  whereas  the  dyestuffs 
which  are  insoluble  in  such  substances  pass  into  the  intercellular 
spaces.  Too  much  stress,  however,  must  not  be  laid  on  these  experi- 
ments. All  these  dyestufis  are  abnormal  so  far  as  the  body  is  concerned. 
We  cannot  imagine  that  at  any  time  in  the  course  of  evolution  of  the 
properties  of  the  intestinal  epithelium  the  cells  were  ever  presented 
with  or  had  to  discriminate  between  different  dyestuffs.  The  fact 
that  absorption  of  these  dyestuffs  is  determined  by  the  physical 
conditions  of  the  cell  membrane  is  no  proof  that  the  absorption  of 
the  normal  food  constituents  is  determined  in  the  same  way.  In 
fact,  it  is  quite  legitimate  to  assume  that  the  lipoid  membrane  or 
limiting  layer  round  every  cell  has  as  its  main  office,  not  the  regula- 
tion of  the  access  of  food-stuffs  to  the  cell,  but  its  protection  from 
any  of  the  food -stuffs  which  it  does  not  require  for  its  metabolism. 
If  it  were  not  for  such  a  membrane  the  assimilation  of  a  salt  would 
be  determined  entirely  by  its  concentration  in  the  immediate  sur- 
roundings of  the  cell,  whereas  we  know  that  the  assimilation  of 
any  living  organism,  whether  uni-  or  multi-cellular,  is  regulated 
in  the  first  place  by  the  activity  of  the  organism  itself.  According 
to  this  activity  and  the  needs  thereby  induced  the  uptake  of  food 
material  may  be  large  or  snuill  whatever  its  concentration  in  the 
surrounding  medium.  It  would  indeed  be  strange  that  the  whole 
absorbing  surface  of  the  intestine  should  be  covered  by  a  membrane, 


830  PHYSIOLOGY 

of  which  the  greater  part  was  useless  for  the  absorption  of  the  common 
food-stufis,  as  would  be  the  case  if  these  could  only  penetrate  the 
membrane  by  the  narrow  chinks  between  the  cells.  It  seems 
more  probable  that  the  absorption  of  the  different  food-stuffs,  and 
probably  also  of  the  normal  salts  of  the  body,  is  effected  by  the  cells 
themselves,  in  accordance  with  their  nutritional  needs,  and  this,  view 
is  strengthened  when  we  come  to  examine  into  the  absorption  even 
of  normal  saline  solutions.  If  50  c.c.  of  normal  sodium  chloride  solution 
be  introduced  into  a  loop  of  intestine,  it  is  absorbed  steadily,  so  that  at 
the  end  of  an  hour  not;  more  than  about  20  c.c.  may  be  recoverable. 
The  absolute  amounts  absorbed  differ  in  various  experiments,  but  are 
fairly  uniform  for  repeated  observations  on  one  and  the  same  animal. 
The  absorption  of  such  a  solution  could  be  ascribed  to  the  osmotic 
pressure  of  the  colloids  in  the  blood  plasma  or  lymph  within  the 
spaces  of  the  villi.  If,  instead  of  using  isotonic  solutions,  hyper- 
tonic solutions  are  employed,  e.g.  a  2  or  3  per  cent.  NaCl  solution, 
absorption  still  takes  place,  but  may  be  preceded  by  an  interval 
in  which  there  is  an  actual  increase  of  the  fluid  contained  in  the 
gut.  Here,  again,  we  might  ascribe  the  absorption  to  the  physical 
factors  present,  were  it  not  that  absorption  is  found  to  commence 
before  the  fluid  in  the  gut  has  attained  isotonicity  with  the  blood. 
In  fact,  employing  a  1-5  per  cent,  salt  solution,  absorption  may  occur 
from  the  very  beginning  of  the  experiment.  If  such '  a  solution  is 
passed  through  the  epithelial  membrane  into  the  blood  plasma  with 
a  smaller  tonicity,  it  is  evident  that  work  must  be  done  in  the  process, 
work  which  can  only  be  furnished  by  the  cells  of  the  epithelium. 
When  sugar  solutions  are  employed  they  behave  in  somewhat  similar 
fashion  to  sodium  chloride  solutions,  provided  that  the  sugar  is  one 
of  the  absorbable  hexoses,  both  sugar  and  water  being  rapidly 
absorbed.  It  is  important  to  note  that  dextrose  is  absorbed  from 
the  gut  almost  as  rapidly  as  sodium  chloride,  and  quite  as  rapidly 
as  sodium  iodide,  although  its  diffusibility  is  very  considerably  less 
than  either  of  these  salts.  Moreover  great  differences  are  found 
between  the  rate  at  which  different  sugars  are  absorbed,  differences 
which  are  not  referable  to  the  diffusibility  of  the  sugars  in  question. 
Thus  the  monosaccharides  glucose,  fructose,  galactose  are  absorbed 
with  double  the  rapidity  of  solutions  of  cane  sugar  and  maltose, 
and  it  seems  that  in  the  absence  of  hydrolytic  splitting  of  the 
disaccharides  absorption  from  the  gut  would  be  entirely  abolished. 
Thus  lactose  disappears  from  the  intestine  much  more  slowly  than 
either  of  the  other  two  disaccharides,  so  that  large  doses  may  give 
rise  to  a  laxative  effect.  In  animals  devoid  of  lactase,  the  lactose- 
splitting  ferment,  in  their  intestinal  epithelium  milk  sugar  is  appar- 
ently not  absorbed  at  all. 


THE  ABSORPTION  OF  THE   FOOD-STUFFS  831 

The  most  cogent  argument  perhaps  in  favour  of  an  active  inter- 
vention of  the  cells  of  the  gut  in  the  process  of  absorption  is  furnished 
by  the  study  of  the  absorption  of  blood  serum.  It  has  been  shown 
that  if  an  animal's  own  serum  be  introduced  into  a  loop  of  its  intestine 
the  serum  undergoes  absorption.  This  absorption  affects  the  water 
and  salts  more  than  the  protein,  so  that  the  percentage  of  the  proteins 
in  the  fluid  remaining  in  the  intestine  is  increased.  Finally,  how- 
ever, the  whole  of  the  serum  is  absorbed.  In  this  case  the  fluid 
within  the  gut  is  identical  with  the  fluid  within  the  blood-vessels. 
There  are  no  differences  in  concentration,  quality  of  salts,  or  osmotic 
pressure  of  proteins.  Nevertheless  water  passes  through  the  cells 
of  the  gut  from  their  inner  to  their  outer  sides,  entraining  with  it 
the  salts  of  the  serum  and  a  certain  proportion  of  the  indiffusible 
proteins.  It  is  impossible  to  explain  this  result  as  due  to  the 
digestion  of  the  proteins  and  their  conversion  into  diffusible  pro- 
ducts, since  the  intestinal  loops  were  washed  free  of  any  trypsin 
that  they  contained,  and  serum  has  itself  a  strong  antitryptic  action 
which  would  prevent  its  being  attacked  by  even  a  strong  solution  of 
trypsin. 

The  active  intervention  of  the  cells  in  the  absorption  of  salt 
solutions,  as  well  as  of  serum,  can  be  abolished  by  any  means  which 
diminishes  or  destroys  their  vitality,  such  as  the  addition  of  sodium 
fluoride  to  the  fluid  to  be  absorbed,  or  destruction  of  the  epithelium 
by  previous  temporary  occlusion  of  the  blood-vessels  supplying  the 
loop  of  intestine. 

We  must  conclude  that,  when  a  fluid  is  introduced  into  the  intes- 
tine, an  active  transference  of  water  from  the  lumen  into  the  blood 
stream  is  effected  by  the  intermediation  of  forces  having  their  origin 
in  the  metabolism  of  the  cells  themselves.  This  work  of  absorption 
of  the  cells  may  be  aided  or  hindered  according  to  the  physical 
conditions  present.  If  these  act  against  the  cells,  e.g.  if  the  fluid 
be  hypertonic,  the  absorption  is  effected  more  slowly,  while  with 
hypotonic  solutions  the  physical  conditions  concur  with  the  vital 
activity  of  the  cells  in  bringing  about  a  very  rapid  transference  of 
fluid  from  the  gut  into  the  blood-vessels.  Among  these  physical 
conditions  we  must  reckon  the  nature  of  the  salts  present  in  the 
solution.  If  these  can  pass  easily  into  and  through  the  cells,  e.g. 
ammonium  salts,  sodium  chloride,  absorption  is  carried  out  rapidly. 
If,  on  the  other  hand,  the  salts  in  the  intestinal  contents  are  but 
slightly  diffusible  or  have  very  little  power  of  penetrating  into  the 
cells,  the  absorption  of  water  by  the  cells  causes  an  increased  con- 
centration of  the  salts,  and  therefore  an  increased  osmotic  pressure, 
which  offers  a  resistance  to  any  further  absorption  and  the  process 
comes  to  an  end,  when  the  absorptive  power  of  the  cells  ia  exactly 


832  PHYSIOLOGY 

balanced  by  the  increased  osmotic  pressure,  or  attraction  for  water, 
of  tbe  intestinal  contents. 

Cushny  and  Wallace,  as  the  result  of  their  experiments  on  the  relative  absorb- 
ability of  salt  solutions  from  the  gut,  divide  the  salts  into  four  main  classes  as 
follows  : 

I  II  III  IV 

Sodium  chloride,  Ethyl  sulphate.  Sulphate,  phosphate,      Oxalate, 

bromide,  iodide,  nitrate,  lactate,  saU-     ferrocyanide,  capry-        fluoride.  . 

formate,  acetate,  cylate,  phthallate.         late,  malonate,  succi- 

propionate,  butjTate,  nate,  malate,  citrate, 

valerianate,  caprate.  tartrate. 

Of  these  the  first  class  contains  those  salts  which  are  absorbed  with  great 
ease  from  the  intestine.  The  second  group  of  salts  are  absorbed  with  somewhat 
greater  difficulty.  The  third  group  are  absorbed  so  slowly,  i.e.  the  salts  retain 
the  water  in  which  they  are  dissolved  so  long,  that  they  increase  peristalsis  and 
act  as  laxatives  or  piugatives.  The  members  of  the  fourth  class  are  not  absorbed 
at  all.  It  is  evident  that  this  classification  is  independent  of  the  diffusibility 
of  the  salts.  Sodium  acetate  has  a  much  smaller  dissociation  value  and  a  lower 
diffusibility  than  sodium  chloride  or  iodide,  and  yet  is  absorbed  at  approximately 
the  same  rate  as  these  two  salts.  There  is,  however,  as  Cuslmy  pointed  out, 
one  physical  or  chemical  character  which  apparently  determines  the  non-absorb- 
ability (relative  or  absolute)  of  the  members  of  the  third  and  fourth  classes. 
All  these  salts  form  insoluble  compounds  with  calcium.  This  common 
character  is  not  an  explanation  of  the  permeability  of  the  cell  wall,  but  is  simply 
a  general  statement  of  one  of  the  conditions  which  affect  the  power  of  the  cells 
to  take  up  salts  from  their  solutions,  this  power  being  absent  in  the  case  of  salts 
which  furnish  an  insoluble  calcium  compound. 


THE  ABSORPTION  OF  FATS 
Fats  administered  to  an  animal  in  excess  of  its  diurnal  require- 
ments are  stored  up  in  the  body  in  the  form  in  which  they  are 
administered.  Each  cell  of  the  body  probably  possesses  in  itself  the 
mechanism  for  the  utilisation  of  these  neutral  fats,  and  for  effecting 
in  them  the  various  changes  involved  in  the  successive  stages  of  their 
disintegration  and  oxidation  through  which  they  are  finally  converted 
to  CO2  and  water.  The  problem  therefore  of  fat  absorption  is 
ultimately  one  of  the  simplest  with  which  we  have  to  deal,  and 
involves  merely  the  transference  of  the  neutral  fat  of  the  food  to 
the  circulating  fluids  in  such  a  form  that  it  can  be  carried  by  them 
to  the  place  where  it  is  required  for  the  metabolism  of  the  body  or 
where  it  may  be  stored  up  as  a  reserve  substance. 

The  processes  of  digestion  of  fat  result  in  the  production  of  glycerin 
and  fatty  acids,  if  the  reaction  be  neutral  or  slightly  acid.  If  the 
reaction  of  the  gut  be  alkaUne  the  alkali  will  combine  with  the  fatty 
acids  to  produce  soaps.  Analyses  of  the  contents  of  the  gut  after 
a  fatty  meal  show  that  the  greater  proportion  of  the  fats  are  present 


THE  ABSORPTION  OF  THE   FOOD-STUFFS  833 

as  a  iiiixtuie  of  fatty  acids  and  soaps,  the  amount  of  these  substances 
as  compared  with  unchanged  fat  increasing  as  we  descend  the  gut. 

In  studying  the  absorption  of  fats  the  investigator  is  able  to 
take  advantage  of  the  fact  that  the  micro-chemical  detection  of  this 
substance  is  usually  very  easy.  Globules  of  fats  or  fatty  acids 
containing  any  proportion  of  the  unsaturated  fatty  acids  have  the 
property  of  reducing  osmic  acid,  and  therefore  of  being  stained 
black  by  this  reagent.  Practically  all  the  fats  which  occur  in  the 
food  or  in  the  cells  of  the  body  contain  oleic  acid  or  the  glyceride 
of  this  acid  in  association  with  palmitic  or  stearic  acid,  and  therefore 
give  the  typical  micro-chemical  fat  reactions.  In  many  cases  it  is 
useful  to  employ  the  specific  stains  for  fats,  such  as  Sudan  red  or 
alkanna  red.  It  is  important  to  remember  that  the  intensity  of 
the  fat  reaction  given  by  a  cell  is  only  an  expression  of  the  fat  or 
fatty  acid  contained  in  a  free  state  in  the  cell,  and  is  no  criterion 
of  the  total  amomit  of  fat  which  may  be  present.  Thus  a  normal 
heart  muscle  in  section  gives  only  a  difiuse  light  brown  coloration 
with  osmic  acid.  After  poisoning  by  phosphorus  or  by  diphtheria 
toxin,  every  muscle -cell  may  be  found  studded  with  minute  black 
granules  of  fat.  Chemical  analysis  shows,  however,  that  the  normal 
heart  muscle  contains  as  much  fat  as  the  degenerated  muscle.  Our 
micro- chemical  methods  will  therefore  throw  no  light  on  the  amount 
of  fat  which  is  actually  in  combination  with  the  cell  protoplasm. 

If  an  animal  be  examined  a  few  hours  after  the  administration 
of  a  meal  rich  in  fats,  the  lymphatics  of  the  intestine  are  seen  to 
be  distended  with  a  milky  fluid — chyle — and  the  same  fluid  is  foimd 
filling  the  cisterna  lympJuUica  inagna  and  the  thoracic  duct.  The 
lymph  from  the  thoracic  duct  will  also  be  milky,  and  chemical  analysis 
shows  that  the  opacity  is  due  to  the  presence  of  minute  granules  of 
neutral  fat.  The  fat  in  such  chyle  may  amount  to  over  6  per  cent.,  so 
that  in  a  moderate-sized  dog  12  grammes  of  fat  may  be  carried  in  the 
course  of  an  hour  from  the  intestine  to  the  blood  by  this  means.  This 
great  access  of  fat  to  the  blood  during  fat  absorption  introduces  corre- 
sponding changes  in  the  blood.  The  plasma  itself  becomes  milky,  and 
if  the  blood  be  allowed  to  clot,  the  serum  expressed  from  the  clot  is 
also  milky.  On  standing,  a  layer  of  fat  globules  like  cream  may  rise 
to  the  surface  of  the  serum.  Fat  is  found  in  a  free  state  in  this  finely 
divided  condition  in  the  blood  plasma  so  long  as  it  is  being  absorbed 
in  the  intestine.  During  starvation  it  disappears  entirely,  the  serum 
becoming  perfectly  clear.  Thus  part,  at  any  rate,  of  the  fat  which  is 
absorbed  from  the  gut  is  carried  thence  by  the  lymphatic  channels  in 
the  form  of  neutral  fat  to  the  blood  stream,  by  which  it  is  distributed 
to  the  various  tissues  of  the  body,  gradually  leaving  the  blood  stream 
in  a  manner  which  at  present  has  not  been  determined.    Not  all  the 

53 


834  PHYSIOLOGY 

fat  which  is  absorbed  takes  this  path  by  way  of  the  lymphatics  and 
the  thoracic  duct.  Ligature  of  the  thoracic  duct,  if  efEective,  certainly 
impedes  the  absorption  of  fat,  but  does  not  aboHsh  it.  If  the  thoracic 
duct  lymph  be  collected  during  the  absorption  of  a  given  quantity  of 
fat  from  the  intestine,  not  more  than  60  per  cent,  of  the  fat  which  has 
disappeared  from  the  gut  can  be  recovered  from  the  lymph.  What 
happens  to  the  remainder  we  do  not  know.  Apparently  it  does  not 
reach  the  blood  in  a  finely  divided  condition.  If  the  thoracic  duct 
be  ligatured  the  percentage  of  fat  in  the  blood  rapidly  falls  to  a 
minimum  which  remains  constant,  even  during  starvation.  If  now 
fat  be  administered,  although  a  considerable  proportion  of  it  may 
A  B 


Fig.  348.  Columnar  epithelium  from  small  intestJDe  of  frog  stained  with 
osmic  acid  to  show  fat-absorption. 
A,  five  hours  after  a  meal  of  olive  oil ;  B,  three  hours  later.  It  should 
be  noticed  that  the  fat  globules  first  formed  grow  in  size  in  the  course  of 
digestion,  pointing  to  a  gradual  deposition  of  fat  on  the  globules  from 
solution  in  the  protoplasm.     (Schafer.)  -^ 

be  absorbed,  the  percentage  of  fat  in  the  blood  is  not  raised.  If 
therefore  the  fat  is  absorbed  directly  into  the  blood  it  cannot  be  in 
the  particulate  condition,  and  it  must  be  in  such  small  quantities 
at  a  time  that  it  is  at  once  removed  from  the  blood  by  the  tissues 
through  which  this  fluid  flows.  It  is  difiicult  to  imagine  that  any 
large  proportion  of  this  lost  fraction  of  the  fat  is  absorbed  into  the 
blood  stream  in  the  form  of  soaps,  since,  as  Munk  has  shown,  soaps 
injected  into  the  blood  stream  act  as  potent  poisons  and  give  rise 
to  a  great  fall  of  blood  pressure,  incoagulability  of  the  blood,  and 
a  condition  of  coma.  We  must  therefore  leave  out  of  account  for 
the  present  the  mechanism  of  absorption  of  this  lost  fraction  and 
endeavour  to  trace  the  course  of  the  absorption  of  that  part  of  the 
fat  which  makes  its  way  into  the  lymphatics. 

Microscopic  examination  of  a  section  of  the  villus  during  fat 
absorption  shows  that  the  absorption  occurs  for  the  most  part  through 
the  epithelial  cells.  These  are  found  closely  packed  with  fat  granules 
(Fig.  348),  which,  small  at  the  beginning  of  the  process  of  absorption, 


THE  ABSORPTION  OF  THE  FOOD-STUFFS  835 

rapidly  enlarge  till  they  occupy  the  greater  part  of  the  cell  lying 
between  the  nucleus  and  the  basilar  striated  border.  Most  observers 
are  agreed  that  no  fat  globules  are  to  be  seen  within  the  border  itself. 

According  to  Altmann  the  fat  granules  found  in  the  cells  during  absorption 
are  themselves  produced  by  a  transformation  of  fuchsinophile  graniiles  which 
are  present  in  the  cell  even  during  the  fasting  condition.  At  an  early  stage 
the  small  fat  granules  can  be  stained  so  as  to  show  a  distinct  fucLsinophile 
envelope.  Altmann  interprets  this  appearance  as  showing  that  the  epitheUal 
cells  take  up  the  fat  in  a  dissolved  form,  probably  in  a  hydrolysed  condition, 

A 


Fig.  349.  a.  Vertical  section  through  intestinal  epithelium  of  a  rat  during 
fat  absorption.  B.  Horizontal  section  through  deeper  parts  of  the  cells, 
showing  excretion  of  fuie  fat  globules  into  the  intercellular  clefts. 
(Reuter.) 

and  that  a  process  of  synthesis  then  occurs  in  the  granules  leading  to  the 
formation  and  accumulation  of  fat.  When  the  process  of  absorption  is 
proceeding  actively  the  meshes  of  the  vUlus  contain  a  number  of  free  fat 
granules,  and  the  leucocytes  in  these  meshes  are  generally  found  also  full  of  these 
granules.  According  to  Zawarykin  and  Schiifcr  an  important  fmiction  in  the 
transfer  of  the  granules  from  cpithehal  cells  to  central  lacteal  was  performed 
by  the  leucocytes.  These  were  supposed  to  take  up  the  fat  granules  extruded 
by  the  epithehal  ceUs  at  the  base  of  the  vilh,  to  wander  into  the  central  lacteal 
where  they  broke  down,  furnisliing  in  this  way  the  molecular  basis  of  the 
chyle  as  weU  as  its  protein  constituents.  This  view  was  strongly  combated  by 
Heideuhain,  who  pointed  out  that  many  of  the  granules  staining  darkly  \nth 
osmic  acid  were  not  necessarily  fat,  and  that  the  number  of  leucocj'tes  -nithin 
the  villi  were  hardly  sufficient  to  accomit  for  the  amount  of  material  observed. 
According  to  Reuter  the  epithelial  cells  take  up  fat  in  a  dissolved  condition 
through  the  striated  border,  and  deposit  it  as  granules  of  neutral  fat  in  the 
inner  portion  of  the  protoplasm.  From  here  the  fat  is  passed  on  by  the  proto- 
plasm by  the  side  of  the  nucleus  and  extruded  in  the  form  of  very  tine  granules 
in  the  deeper  parts  of  the  inter-epithelial  clefts,  wliich  thus  fiuictioa  as  true 
excretory  channels  for  the  epithehal  cells  (Fig.  349). 


836  PHYSIOLOGY 

It  is  probable  that  the  muscular  mechanism  of  absorption 
described  many  years  ago  by  Briicke  plays  an  important  part  in  the 
absorption  of  fats,  but  it  is  difficult  to  furnish  any  experimental 
proof  of  the  manner  in  which  this  mechanism  works.  Repeated 
contractions  of  the  muscle  fibres  of  the  villus  would  tend  to  empty 
the  spaces  into  the  central  lacteal,  and  this  in  its  turn  into  the  sub- 
mucous plexus  of  lymphatics,  so  that  the  lymph  in  the  spaces  is 
constantly  renewed  and  passes  laden  with  absorbed  fat  particles 
into  the  valved  lymphatics  of  the  meseiitery. 

It  was  long  considered  that  the  fats  were  taken  up  by  the  epithelial 
cells  from  the  intestine  as  fine  particles  of  neutral  fat,  the  chief  use 
of  the  pancreatic  juice  being  to  aid  the  formation  of  an  emulsion 
of  fat  in  the  intestines.  There  seems  to  be  little  doubt  that  this 
was  an  error,  and  that  the  fats  are  absorbed,  dissolved  in  the  bile, 
either  as  soap  or  as  fatty  acid.  The  arguments  for  this  view  can  be 
shortly  summarised  as  follows  : 

(1)  Although  the  bile  does  not  dissolve  neutral  fats,  it  has  a 
strong  solvent  action  on  fatty  acids,  on  soaps,  and  even  on  the 
insoluble  calcium  soaps.  This  solvent  power  is  greatest  in  the  case 
of  oleic  acid,  of  which  bile  can  dissolve  19  per  cent.  It  is  very  small 
in  the  case  of  pure  stearic  acid,  but  the  solubility  of  the  latter  acid 
is  largely  increased  if  it  be  associated  as  usual  with  oleic  acid.  Moore 
has  shown  that  this  solvent  action  is  chiefly  conditioned  by  the  bile 
salts,  aided  by  the  lecithin  and  cholesterin  also  present  in  the  bile,  a 
solution  of  lecithin  and  cholesterin  in  bile  salts  having  a  greater 
solvent  power  than  the  salts  alone. 

(2)  The  presence  of  bile  in  the  intestine  is  essential  for  the  normal 
absorption  of  fat.  If  the  bile  be  cut  off  by  occlusion  of  the  bile 
ducts  or  by  the  estabhshment  of  a  biliary  fistula,  the  utihsation  of 
fat  sinks  from  about  98  per  cent,  to  about  40  per  cent.,  the  unabsorbed 
fat  appearing  in  the  faeces.  This  large  undigested  residue  of  fat 
hinders  also  the  absorption  of  the  other  food-stuffs  by  covering  them 
with  an  insoluble  layer,  so  that  nutrition  as  a  whole  may  suffer  con- 
siderably. 

(3)  Absorption  may  also  be  interfered  with  by  ligature  of  the 
pancreatic  duct.  This  result  is  probably  due  to  the  absence  of  the 
fat-sp fitting  ferments  of  the  pancreatic  juice  from  the  intestine.  If 
the  faeces  be  analysed  it  is  found  that  a  very  large  proportion  of  the 
fat  has  been  split  into  fatty  acids  in  the  course  of  its  passage  through 
the  alimentary  canal.  This  lipolysis  has,  however,  been  carried  out  by 
the  agency  of  micro-organisms,  i.e.  in  the  lower  segments  of  the  gut 
where  the  greater  part  of  the  bile  has  been  already  re-absorbed  into 
the  portal  circulation.  If  fat  be  given  to  animals  deprived  of  theii 
pancreas,  in  a  finely  divided  form,  such  as  cream  or  milk,  a  certain 


THE  ABSORPTIOX  OF  THE  FOOD-STUFFS  837 

proportion  of  it  is  absorbed.  Under  these  conditions  a  considerable 
degree  of  lipolysis  may  occur  in  the  stomach  itself,  so  that  the  fats 
would  be  already  hydro lysed  when  they  came  in  contact  with  the 
bile  in  the  duodenum. 

(4)  It  was  shown  by  Schiff,  by  means  of  his  amphobolic  fistula, 
that  the  bile  which  is  poured  into  the  gut  undergoes  a  circulation, 
being  re-absorbed  from  the  lower  parts  of  the  digestive  tube,  carried 
to  the  liver  by  the  portal  vein,  and  re-secreted  in  the  bile.  The 
same  quantity  of  bile  salts  may  therefore  be  used  over  and  over 
again  as  a  vehicle  for  the  transfer  of  the  fatty  acid  and  soaps  from 
the  lumen  of  the  gut  into  the  epithelial  cells. 

(5)  Substances  which  are  physically  almost  identical  with  fats, 
e.g.  petroleimi  or  paraffin,  are  not  absorbed  even  when  introduced 
into  the  intestine  in  the  finest  possible  emulsion.  If  neutral  fat 
be  melted  with  a  soft  paraffin  and  the  resulting  mixture  made  into 
a  fijie  emulsion  and  administered,  it  is  found  that  the  intestine  rejects 
the  paraffin,  but  takes  up  the  neutral  fat.  This  result  can  only  be 
explained  by  assuming  that  the  fat  in  the  particles  has  been  actually 
dissolved  out  by  the  digestive  juices  and  has  been  absorbed  in  a  state 
of  solution. 

We  may  sum  up  the  processes  involved  in  digestion  and  absorp- 
tion of  fat  as  follows.  Neutral  fat  is  hydrolysed  into  fatty  acid  and 
glycerin  under  the  action  of  the  gastric  juice,  the  pancreatic  juice, 
and  the  succus  entericus,  the  effect  of  the  gastric  juice  being,  how- 
ever, extremely  Umited  unless  the  fat  be  presented  to  it  in  a  finely 
divided  condition.  The  lipolytic  action  of  the  pancreatic  juice  and 
succus  entericus  is  largely  aided  and  increased  by  the  simul- 
taneous presence  of  bile,  which,  in  virtue  of  the  bile  salts  lecithin 
and  cholesterin  it  contains,  enables  the  pancreatic  juice  to  enter 
into  close  relation  with  the  fat,  and  dissolves  the  products  of  the 
activity  of  the  ferment,  and  so  enables  it  to  attack  renewed  portions 
of  the  neutral  fat.  As  the  result  of  this  lipolysis  there  are  formed 
glycerin,  which  is  soluble  in  water,  and  fatty  acids  or  soaps,  according 
as  the  reaction  of  the  medium  is  acid  or  alkaline.  The  alkaline 
soaps  are  soluble  in  water,  the  soaps  of  magnesium  and  calcium  are 
soluble  in  bile,  free  fatty  acids  are  soluble  in  bile  acids.  The  fat 
is  thus  reduced  to  a  condition  in  which  it  is  soluble  in  the  intestinal 
contents  whatever  their  reaction.  In  this  state  of  solution  its  con- 
stituents are  taken  up  by  the  cells  of  the  intestinal  mucosa.  Within 
the  cells  a  process  of  synthesis  takes  place,  the  soaps  being  split 
and  the  fatty  acids  thus  set  free  or  absorbed,  being  combined  with 
glycerin  with  the  elimination  of  water  to  fonn  neutral  fat,  which 
appears  as  fine  granules  in  the  cell  protoplasm.  By  an  active  process 
of  excretion  these  granules  are  extruded  in  a  somewhat  more  finely 


838  PHYSIOLOGY 

divided  form  into  the  intercellular  clefts  and  into  the  spaces  of  the 
villus,  whence  by  the  contractions  of  the  musculature  of  the  villus 
they  are  forced  with  the  lymph  transuding  from  the  capillary  blood- 
vessels into  the  central  lacteal,  and  thence  along  the  mesenteric 
lymphatics  to  the  thoracic  duct.  This  description  would  apply 
to  about  GO  per  cent,  of  the  fat  which  is  absorbed.  It  is  probable 
that  all  the  fat  which  is  absorbed  is  taken  up  in  a  dissolved  condition, 
but  whether  the  remaining  40  per  cent,  enters  the  blood  stream, 
or  is  utilised  and  broken  down  in  the  tissues  of  the  intestinal  wall 
itself,  we  have  no  means  of  judging.  Under  normal  circumstances 
the  utiUsation  of  fat  is  almost  complete.  By  the  time  the  intestinal 
contents  have  arrived  at  the  lower  end  of  the  ileum  95  per  cent,  of 
the  fat  has  been  absorbed.  Removal  of  the  whole  large  intestine 
was  found  by  Vaughan  Harley  not  to  afEect  fat  absorption. 

THE   ABSORPTION  OF  CARBOHYDRATES 

As  a  result  of  the  action  of  the  various  digestive  juices  all  the 
carbohydrate  constituents  of  the  normal  diet  of  man  are  reduced 
to  the  state  of  monosaccharides.  The  absorption  of  these  digestive 
products  may  take  place  at  any  part  of  the  alimentary  canal,  the 
greatest  part  in  the  act  of  absorption  being  taken  by  the  small 
intestine.  By  the  time  that  the  food  has  arrived  at  the  ileocsecal 
valve  practically  the  whole  of  the  carbohydrate  constituents  of  the 
food  have  been  absorbed.  All  experimenters  are  agreed  that  the 
carbohydrates  pass  into  the  body  "by  way  of  the  vessels,  of  the  portal 
system.  The  lymph  from  the  thoracic  duct  contains  no  more  sugar 
than  does  the  arterial  blood  taken  at  the  same  time,  whereas  several 
observers  have  obtained  an  increased  percentage  of  sugar  in  the 
portal  blood  during  the  absorption  of  a  big  carbohydrate  meal. 

Of  the  carbohydrates  of  the  food,  some,  like  starch,  dextrin, 
glycogen,  are  colloidal  and  indiffusible ;  others,  such  as  the 
disaccharides  cane  sugar,  milk  sugar,  and  maltose,  are  soluble  and 
diffusible,  and  the  products  of  the  action  of  digestive  ferments  on 
these  two  classes,  namely,  monosaccharides,  mannose,  fructose, 
glucose,  galactose,  are  also  soluble  and  diffusible.  The  problem 
as  to  the  mechanism  involved  in  the  passage  of  these  substances 
across  the  intestinal  wall  into  the  blood-vessels  has  been  already 
dealt  with  in  treating  of  the  absorption  of  water  and  salts.  The 
most  striking  fact  is  the  relative  impermeability  of  the  intestinal 
wall  to  the  disaccharides  as  compared  with  the  monosaccharides. 
The  intestinal  wall  is  apparently  only  able  to  take  up  in  any  quantity 
such  sugars  as  can  be  utilised  by  the  cells  of  the  organism.  For 
this  purpose  the  disaccharides  are  useless  ;  cane  sugar  or  lactose 
introduced  into  the   blood-vessels    or    subcutaneously   is    excreted 


THE  ABSORPTION  OF  THE  FOOD-STUFFS  839 

quantitatively  in  the  urine,  and,  as  might  be  expected,  does  not 
increase  in  any  way  the  glycogen  of  the  liver.  When  maltose  is 
injected  in  the  same  manner  a  certain  proportion  of  it  is  utilised 
owing  to  the  fact  that  the  blood  and  fluids  of  the  body  contain  a 
ferment,  maltase,  capable  of  converting  the  disaccharide  into  the 
monosaccharide,  glucose.  The  absorption  of  these  disaccharides 
occurs  therefore  much  more  slowly  from  the  intestine  than  does  the 
absorption  of  monosaccharides,  the  process  of  absorption  being 
always  preceded  by  and  waiting  for  the  process  of  hydrolysis.  Thus 
huge  doses  of  cane  sugar  may  be  taken  without  causing  the  appear- 
ance of  cane  sugar  in  the  blood  or  urine.  It  has  been  found  that 
sugar  does  not  appear  in  the  urine  until  as  much  as  320  grm.  of  cane 
sugar  have  been  ingested,  whereas  any  quantity  of  glucose  over 
100  grm.  may  give  rise  to  glycosuria.  Lactose  is  absorbed  still  more 
slowly,  and  in  animals  whose  intestine  is  free  from  the  ferment  lactase, 
is  not  absorbed  ;  large  doses  of  lactose  in  such  animals  therefore  give 
rise  to  diarrhoea.  The  behaviour  of  the  intestinal  wall  to  the  non- 
assimilable sugars  of  artificial  origin  has  not  yet  been  sufficiently 
investigated.  It  would  be  interesting  to  inquire  whether  the  rate  of 
absorption  of  the  different  sugars  was  in  any  way  determined  by  their 
stereomeric  configuration,  whether,  for  instance,  ^glucose  would  be 
absorbed  as  rapidly  as  the  ordinary  d-ghicose. 

THE  ABSORPTION  OF  PROTEINS 
In  very  few  departments  of  physiology  has  there  been  so 
great  a  revolution  in  our  ideas  as  in  that  relating  to  protein 
absorption,  especially  as  to  the  form  in  which  it  is  absorbed  from 
the  alimentary  canal,  and  its  fate  after  absorption.  As  to  the  channel 
by  which  it  obtains  entry  into  the  circulation,  practical  agreement 
reigns  that  it  is  absorbed  by  the  blood-vessels.  Almost  every  physio- 
logist who  has  occupied  himself  with  the  investigation  of  the  lymph 
flow  from  the  thoracic  duct  has  been  impressed  by  the  fact  that  the 
variations  in  the  amount  of  lymph  to  be  obtained  in  this  way  bear 
no  relation  to  the  condition  of  the  animal  as  regards  the  state  of 
digestion.  Nor  do  we  find  any  appreciable  increase  in  the  amount 
of  lymph  flow^  or  in  the  amount  of  proteins  contained  in  this  hmph 
during  digestion.  The  small  increase  observed  by  Asher  and  Barbera 
would  be  sufficiently  accounted  for  by  the  increased  blood-supply 
to  the  intestines  during  digestion,  and  is  insufficient  to  account  for 
the  absorption  of  any  appreciable  quantity  of  the  protein  which 
is  being  taken  up  from  the  alimentary  canal.  Moreover  it  was 
shown  by  Schmidt  Miilheim  that  the  absorption  of  proteins  was  not 
interfered  with  as  the  result  of  ligature  of  the  thoracic  d\ict,  and  that 
after  this  duct  had   been   ligatured  the  ingestion  of    proteins  was 


840  PHYSIOLOGY 

followed  at  the  usual  interval  by  the  increased  output  of  urea  which 
is  the  invariable  concomitant  of  protein  absorption  and  assimilation. 
We  must  therefore  conclude  that  the  products  of  protein  digestion 
are  taken  up  by  the  epithelial  cells  and  passed  on  by  these  into  the 
blood-vessels.  During  the  absorption  of  a  protein  meal  changes  have 
been  described  by  various  observers  in  the  structures  of  the  villus. 
In  nearly  every  case  there  is  marked  increase  in  the  number  of  mitotic 
figures  in  the  epitheUum  lining  the  folUcles  of  Lieberldihn.  According 
to  Hofmeister  there  is  during  absorption  an  increase  in  the  number 
of  leucocjrtes  in  the  villi,  and  this  observer  ascribed  an  important 
function  to  these  leucocytes  in  the  absorption  of  protein.  Heidenhain 
showed  that  this  increase  of  leucocytes  was  not  constant  in  all  animals, 
and  bore  no  relation  to  the  amount  of  absorption  that  was  taking 
place,  and  was  quite  inadequate  to  account  for  the  total  absorption 
that  was  being  carried  on.  On  the  other  hand,  several  observers 
have  described  changes  in  the  epithelium  as  the  result  of  protein 
digestion.  According  to  Renter  the  epithehal  cells  become  swollen, 
their  protoplasm  stains  less  deeply,  and  at  their  basal  ends  the  cells' 
hmits  disappear,  the  protoplasm  being  apparently  distended  with 
hyaline  coagulable  material  (Fig.  350).  Renter  regards  this  appearance 
as  a  direct  expression  of  the  taking  up  of  proteins  in  a  dissolved 
form  and  their  conversion  near  the  bases  of  the  cells  into  coagu- 
lable proteins  ;  but  further  evidence  on  this  subject  is  necessary 
before  we  can  attach  much  importance  to  such  an  interpretation 
of  the  appearances  observed. 

Under  the  influence  of  the  gastric  juice  the  proteins  of  the 
food  are  resolved  during  their  stay  in  the  stomach  into  albumoses 
and  peptones.  In  the  small  intestine  the  process  of  hydration 
is  carried  further,  the  trypsin  of  the  pancreatic  juice  carrying  the 
proteins  through  the  stage  of  secondary  albumoses  and  peptones, 
and  converting  them  into  a  mixture  of  amino-acids  and  polypeptides. 
The  same  end-products  result  from  the  action  of  the  erepsin  of  the 
intestinal  wall  on  the  albumoses  and  peptones  produced  by  gastric 
digestion.  The  digestive  juices  finally  reduce  the  proteins  therefore 
to  a  mixture  of  amino-acids,  with  a  certain  remainder  of  polypeptides 
consisting  of  two  or  three  of  the  amino-acids  associated  together, 
which  do  not  undergo  further  disintegration  under  the  action  of  the 
intestinal  ferments.  The  final  products  give  no  biuret  test.  The  first 
question  we  have  to  decide  is  to  what  extent  the  proteins  are  reduced 
to  their  ultimate  hydration  products  before  absorption.  We  have 
evidence  that  protein  may  be  absorbed  by  the  small  intestine  without 
having  undergone  any  hydration  whatsoever.  The  absorption  of 
serum  protein  has  been  discussed  already  in  deahng  with  the  mechanism 
of  absorption  of  salt  solutions  from  the  gut.     In  a  series  of  experi- 


THE  ABSORPTION  OF  THE  FOOD-STUFFS 


841 


ments  made  by  Friedlander  the  absorptions  of  various  proteins  were 
compared  after  their  introduction  into  loops  of  the  small  intestine 
which  had  been  washed  free  from  ferment.  During  a  period  of  three 
hours  this  author  found  that  21  per  cent,  of  the  proteins  of  egg  white 
or  of  blood  serum  were  absorbed.  During  the  same  period,  of 
alkaU-albumen  which  had  been  introduced  into  the  loops,  69  per 
cent,  was  absorbed.     On  the  other  hand,  when  STntonin  and  casein 


II 


mV'         'TT^^.^': 


Fig,  350.     Figures  (from  Reuter)  showing  changes  in  intestinal  epithelium 

induced  by  absorption  of  protein. 

I,  epithelium  of  fasting  rat  j  II,  initial  stage ;  III,  later  stage  of  protein 

absorption. 


were  introduced  into  the  intestine,  no  absorption  whatever  was 
observed.  As  to  the  condition  in  which  such  unchanged  protein 
reaches  the  blood  stream  our  knowledge  is  still  imperfect. 
Foreign  proteins,  such  as  egg  albumin,  or  the  serum  of  other  species 
introduced  into  the  blood  stream,  may  cause  poisonous  effects, 
and  give  rise  to  albuminuria,  to  lowering  of  blood  pressure,  or  to 
alteration  of  the  coagulability  of  the  blood.  If  injected  in  small 
quantities  they  excite,  as  a  reaction  on  the  part  of  the  organism,  the 
production  in  the  blood  serum  of  a  precipitin,  and  the  presence  of 


842  PHYSIOLOGY 

the  precipitin  may  be  looked  upon  therefore  as  a  test  by  which 
we  may  decide  whether  these  proteins  have  passed  through  the 
intestinal  wall  unchanged.  In  most  cases  it  is  found  that,  however 
abundant  the  amount  of  protein  administered  in  the  soluble  form, 
none  of  it  appears  in  the  urine,  nor  is  any  precipitin  formation  aroused. 
AscoH  has,  however,  observed  such  events  occasionally  to  follow 
the  administration  of  large  doses  of  egg  white,  and  it  has  been 
shown  that  there  is  a  difference  in  the  behaviour  of  animals  to  the 
introduction  of  soluble  protein  into  their  alimentary  canal,  according 
as  they  are  new  born  or  are  more  than  a  few  days  old.  It  seems 
that  during  the  first  few  days  of  life  the  cellular  lining  of  the  alimen- 
tary canal  is  permeable  to  foreign  proteins,  whereas  later  on  any 
protein  which  is  taken  up  unchanged  from  the  gut  does  not  arrive 
in  the  same  unchanged  condition  in  the  blood  stream. 

The  absorption,  however,  of  unchanged  proteins  can  play  but 
a  small  part  in  the  assimilation  of  protein  as  a  whole.  Animals 
very  rarely  take  coagulable  proteins  in  a  condition  in  which  they 
will  arrive  at  the  small  intestine  in  a  state  of  solution  unchanged. 
Even  in  the  carnivora  the  hving  tissues  taken  into  the  stomach  will 
undergo  coagulation  by  the  acid,  and  will  then  be  dissolved  by  the 
gastric  juice.  In  man  practically  all  the  proteins  of  the  food  are 
either  insoluble  or  are  rendered  insoluble  by  the  process  of  cooking. 
For  absorption  to  take  place  it  is  therefore  necessary  that  this  insoluble 
or  coagulated  protein  should  be  brought  into  solution,  and  this 
process  is  accomplished,  together  with  hydration,  by  means  of  the 
ferments  of  the  gastric  and  pancreatic  juices.  This  process  of  solution 
has  long  been  regarded  as  the  chief  object  of  the  digestive  ferments. 
Although  both  Kiihne  and  Schmidt  Miilheim  were  aware  of  the 
production  of  amino-acids,  such  as  leucine  and  tyrosine,  as  the  result 
of  digestion,  they  regarded  their  production  as  evidence  of  a  waste 
of  material.  Albumoses  and  peptones  are  soluble,  diffusible,  and 
rapidly  absorbed  from  the  ahmentary  canal,  and  there  is  no  doubt 
that  a  large  proportion  of  the  products  of  protein  digestion  are  taken 
up  by  the  absorbing  membrane  in  this  form.  For  many  years  the 
physiologists  were  occupied  with  the  problem  as  to  the  fate  of  these 
peptones  and  albumoses  after  their  entrance  into  the  mucous  mem- 
brane. They  do  not  pass  as  such  into  the  blood.  The  injection  of 
small  quantities  of  albumose  and  peptone  into  the  blood  gives  rise  to 
the  excretion  of  these  substances  by  the  kidneys  ;  injection  of  larger 
quantities  has  pronounced  poisonous  effects,  which  were  first  studied 
by  Schmidc  Miilheim  and  Fano.  If  samples  of  blood  be  taken 
either  from  the  portal  vein  or  from  the  general  circulation  after  a 
heavy  protein  meal,  no  trace  either  of  albumose  or  of  peptone  is  to 
be  found  in  the  blood.     The  observations  of  Hofmeister  and  others 


THE  ABSORPTION  OF  THE  FOOD-STUFFS  843 

to  the  contrary  depend  on  the  fact  that  these  observers  employed 
a  method  for  the  separation  of  coagulable  protein,  as  an  antecedent 
to  the  testing  for  albmnoses,  which  was  in  itself  capable  of  producing 
small  traces  of  these  substances.  Hofmeister  showed  that  during  the 
absorption  of  a  protein  meal  the  mucous  membrane  either  of  the 
stomach  or  of  the  intestine,  if  rapidly  killed  by  plungmg  into  boiling 
water  directly  it  was  taken  from  the  animal,  always  contained  a 
considerable  amount  of  peptone,  and  similar  observations  were  made 
by  Neumeister.  If,  however,  the  mucous  membrane  was  kept  warm 
for  half  an  hour  after  removal  from  the  body,  the  peptone  disappeared. 
Salvioli,  under  Ludwig's  guidance,  introduced  peptone  into  a  loop 
of  gut  which  was  kept  alive  by  passing  defibrinated  blood  through 
its  vessels.  At  the  end  of  some  hours  the  loop  was  found  to  contain 
a  certain  amount  of  coagulable  protein,  but  no  trace  of  peptone,  nor 
was  any  trace  of  the  latter  substance  found  in  the  blood  which  had 
been  passed  through  the  vessels.  These  observations  were  inter- 
preted as  pointing  to  a  regeneration  in  the  intestinal  wall  of  coagulable 
protein  from  the  albumose  and  peptone  taken  up  from  the  gut,  and 
opinions  were  divided  whether  the  most  important  part  of  this 
regeneration  was  to  be  ascribed  to  the  leucocytes  of  the  villi  (Hof- 
meister), or  to  the  epithelial  cells  of  the  mucous  membrane  itself. 

It  is  evident  that  such  a  conclusion  was  not  justified  by  the 
experiments.  All  that  these  experiments  showed  was  that  the 
albimioses  and  peptones  disappeared,  i.e.  were  converted  into  some- 
thing which  did  not  give  the  biuret  test.  The  discovery  of  the 
ferment  erepsin  by  Cohnheim  led  this  observer  to  repeat  the  experi- 
ments of  Hofmeister  and  Neumeister  with  a  \'iew  to  testing  the 
conclusions  drawn  by  these  physiologists.  Cohnheim  found  that, 
although  it  was  perfectly  true  that  albumose  and  peptone  disappeared 
when  intestinal  mucous  membrane  and  peptone  were  placed  together 
in  the  presence  of  either  blood  or  of  Ringer's  fluid,  this  disappearance 
was  due,  not  to  a  regeneration  of  coagulable  protein,  but  to  the  fact 
that  the  erepsin  of  the  mucous  membrane  carried  the  process  of 
hydrolysis  a  step  further,  converting  the  albumoses  and  peptones 
into  the  ultimate  crystalhne  products  of  protein  hydrolysis.  Similar 
observations  were  made  by  Kutscher  and  Seemaiin.  who  showed 
that  at  any  time  after  a  protein  meal  these  end-products,  especially 
leucine,  tyrosine,  lysine,  and  arginine,  were  to  be  found  in  the  contents 
of  the  small  intestine.  A  repetition  of  Sahioli's  experiment  by 
Cathcart  and  Leathes  deprived  this  also  of  much  of  its  significance. 
It  was  found  that  the  artificial  circulation,  although  sufficient  to 
maintain  the  activity  of  the  muscular  wall  of  the  intestine,  as  evidenced 
by  the  peristaltic  movements,  was  insufficient  to  keep  the  mucous 
membrane  ahve.     After  one  hour's  experiment  the  loop  contained 


844  PHYSIOLOGY 

a  mass  of  epithelial  cells  mixed  with  the  products  of  the  action  of 
erepsin  on  the  introduced  peptone  solution.  In  no  case  was  there 
any  diminution  in  the  amount  of  uncoagulable  nitrogen,  i.e.  there 
was  no  formation  of  coagulable  protein,  while  the  processes  of  absorp- 
tion had  been  brought  by  the  desquamation  entirely  to  a  standstill. 

These  additional  experiments  caused  a  complete  revolution  in 
the  attitude  of  physiologists  towards  the  problem  of  protein  absorp- 
tion. All  this  evidence  went  to  show  that  protein,  however  intro- 
duced, whether  as  coagulated  protein  or  as  albumose  and  peptone, 
underwent  complete  hydrolysis  either  in  the  gut  or  in  the  wall  of 
the  gut  before  entering  the  blood  stream.  If  this  were  the  case, 
it  should  be  possible  to  feed  an  animal  on  a  diet  in  which  the  necessary 
protein  had  been  replaced  by  the  corresponding  amount  of  ultimate 
products  of  protein  hydrolysis,  i.e.  by  a  mixture  which  would  give 
no  biuret  reaction.  Such  a  possibility  had  previously  been  negatived 
on  theoretical  grounds  by  Kiihne  and  by  Bunge.  It  was  thought 
by  these  observers  either  that  the  animal  body  lacked  the  power  of 
synthesis  of  proteins  from  these  crystalline  products  (hydration 
products),  or  that  any  complete  hydration  occurring  in  the  intestine 
would  involve  such  a  loss  of  energy  to  the  body  as  to  be  unteleo- 
logical.  Neither  of  these  theoretical  objections  is  justified  in  fact. 
We  know  from  the  researches  of  Fischer  and  others  that  although 
the  different  proteins  in  our  food  present  a  marvellous  quahtative 
simiUtude,  in  that  all  of  them  yield  on  hydrolysis  the  same  kinds 
of  amino-acids,  there  are  great  differences  in  the  relative  amounts 
of  these  amino-acids  contained  in  different  proteins.  Thus,  in 
gelatin,  glycine  is  contained  in  considerable  quantities,  but  is 
absent  in  many  of  the  other  proteins.  Caseinogen  is  distmguished 
by  the  large  amount  of  leucine  that  it  yields,  while  gliadin,  the  chief 
protein  of  wheat  flour,  contains  very  large  amounts  of  glutamic  acid. 
It  is  difl&cult  to  imagine  how,  for  instance,  muscle  protein  could  be 
formed  from  wheat  protein,  a  process  continually  occurring  in  the 
growing  animal,  unless  we  assumed  that  the  protein  molecule  is  first 
entirely  taken  to  pieces,  and  that  its  constituent  molecules  are  then 
selected  by  the  growing  cells  of  the  body  and  built  up  in  the  order 
and  proportions  which  are  characteristic  of  muscle  protein.  More- 
over, when  we  measure  the  amount  of  energy  change  involved  in 
the  hydrolysis  of  the  proteins,  we  find  it  is  relatively  small.  There 
is  not  a  loss  of  5  per  cent,  of  the  total  energy  available,  i.e.  the  heat 
of  combustion  of  the  products  of  pancreatic  digestion  would  differ 
from  that  of  the  original  protein  submitted  to  digestion  by  less  than 
5  per  cent.  The  energy  of  the  protein  as  evolved  in  the  body  lies,  not 
in  the  coupling  of  the  amino-acids  with  one  another,  or  indeed  in  the 
coupling  of  the  nitrogen  to  the  carbon,  but,  hke  that  of  the  other 


THE  ABSORPTION  OF  THE  FOOD- STUFFS  845 

food-stufEs,  in  the  carbon  itself,  and  is  derived  from  the  combustion 
of  the  carbon  of  the  molecule  under  the  influence  of  the  oxidising 
processes  of  the  body  into  carbon  dioxide.  The  experimental  decision 
of  this  question  was  first  attempted  by  0.  Loewi,  who  found  that  it 
was  possible  to  keep  a  dog  in  a  state  of  nitrogenous  equilibrium  on 
a  diet  containing  fat,  starch,  and  a  pancreatic  digest  of  protein  which 
contained  no  substances  which  would  give  the  biuret  test.  These 
results  have  been  confirmed  for  carnivora  by  Henderson,  by  Luthje, 
by  Abderhalden  and  Rona,  and  by  Henriques  and  Hansen.  According 
to  Abderhalden,  it  is  possible  to  keep  an  animal  alive  when  the 
nitrogen  in  his  food  is  represented  entirely  by  the  end-products  of 
pancreatic  digestion.  The  same  result  cannot  be  attained  by  the 
administration  of  the  products  of  acid  hydrolysis  of  protein,  but 
this  may  be  due  either  to  the  racemisation  of  the  amino-acids  under 
the  action  of  the  strong  acid,  or  to  the  fact  that  the  acid  splits  up 
certain  polypeptide  groupings  which  are  still  contained  in  the  trypsin 
digest,  and  which  possibly  cannot  be  synthctised  by  the  cells  of  the 
body. 

We  are  justified  therefore  in  concluding  that  while  a  certain 
small  proportion  of  the  proteins  of  the  food  may  be  absorbed  un- 
changed, a  much  larger  proportion  is  taken  up  as  albumoses  and 
peptones  or  as  amino-acids.  The  albumoses  and  peptones  are,  how- 
ever, rapidly  changed  in  the  mucous  membrane  itself  into  amino-acids, 
which  we  may  regard  as  the  form  in  which  practically  all  the  protein 
of  the  body  is  presented  to  the  absorbing  mechanisms  of  the  alimentary 
canal  for  absorption  and  for  passing  on  into  the  circulating  fluids. 

THE  FATE  OF  THE  AMINO-ACIDS  AFTER  ABSORPTION  BY 
THE  INTESTINAL  EPITHELIUM.  During  a  condition  of  starvation 
the  normal  protein  requirements  of  the  body,  or  rather  of  the  active 
tissues,  are  met  at  the  expense  of  the  less  active  tissues.  The  protein 
characteristic  of  any  tissue  can  be  taken  down,  removed  to  another 
part  of  the  body,  and  built  up  into  the  protein  characteristic  of  some 
other  active  tissue.  It  is  difficult  to  conceive  that  such  a  transference 
and  transformation  could  occur  in  any  other  way  than  by  a  more 
or  less  thorough  disintegration  of  the  protein  molecule  at  one  place 
and  its  synthesis  at  the  other,  and  we  know  from  the  researches  of 
Hedin  and  others  that  every  tissue  contains  intracellular  ferments 
which  are  capable  of  effecting  the  disintegration  of  the  protein  mole- 
cule, and  are  responsible  for  the  autolytic  degeneration  of  tissues 
after  death.  If  therefore  the  normal  interchange  of  protein  between 
the  tissues  is  accomphshed,  as  we  know  it  to  be  in  plants,  by  the 
disintegration  of  the  proteins  into  their  constituent  amino-acids 
and  their  subsequent  reintegration,  there  is  no  a  priori  reason  to 
believe  that  the  blood  carries  the  proteins  from  the  alimentary  canal 


846  PHYSIOLOGY 

to  the  tissues  in  any  other  form  than  that  of  amino-acids.  The 
experimental  proof  of  this  conclusion  meets  with  many  difficulties. 
So  great  is  the  total  volume  of  blood  circulating  through  the  vessels 
of  the  ahmentary  canal  during  the  hours  that  the  observation  is 
taking  place  that  a  considerable  amount  of  amino-acids  could  be 
carried  by  this  blood  from  the  canal  to  the  tissues  without  effecting 
a  change  in  the  composition  of  the  fluid  which  is  within  our  errors 
of  analysis.  The  experimental  investigation  of  this  point  has  been 
attempted  by  Kutscher  and  Seemann,  and  by  Cathcart  and  Leathes. 
The  former  observers  analysed  the  portal  blood  during  active  protein 
digestion  after  cutting  out  by  ligature  the  circulation  from  all  parts 
of  the  body  except  the  heart,  lungs,  liver,  and  ahmentary  canal. 
They  were  unable  to  detect  any  increase  in  the  amount  of  amino- 
acids  in  the  blood.  Cathcart  and  Leathes  investigated  the  content 
of  the  blood  in  soluble,  i.e.  non-protein  nitrogen,  in  normal  animals 
and  in  anaesthetised  animals  in  whom  large  quantities  of  peptone 
solution  had  been  introduced  into  the  small  intestine,  and  found 
a  distinct  increase  in  the  latter  case.  In  this  experiment  the  rate 
of  absorption  of  the  products  of  protein  digestion  was  increased 
much  above  its  normal  value,  whereas  in  the  experiments  of 
Kutscher  and  Seemann  the  rate  of  absorption  in  consequence  of  the 
operative  procedure  was  probably  less  than  would  obtain  in  the 
normal  animal  after  such  a  protein  meal.  The  evidence  therefore, 
so  far  as  it  goes,  is  in  favour  of  part,  at  any  rate,  of  the  protein  being 
carried  by  the  blood  to  the  tissues  in  the  form  of  amino-acids. 

The  negative  results  obtained  by  Kutscher  and  Seemann  sug- 
gested to  these  observers  that  possibly  some  process  of  integration 
might  occur  in  the  mucous  membrane  of  the  ahmentary  canal  itself, 
and  they  were  strengthened  in  this  conclusion  by  the  fact  that  although 
no  amino-acids  could  be  extracted  from  the  intestinal  wall,  they  were 
able,  after  treating  the  mucous  membrane  with  acid,  to  extract 
leucine,  a  fact  suggesting  that  the  leucine  had  been  combined  in  some 
ester-like  compound  with  some  other  constituent  of  the  mucous 
membrane.  Abderhalden  is  inclined  to  believe  that  there  is  an  actual 
regeneration  of  the  protein  in  the  mucous  membrane,  a  formation 
from  the  amino-acids  of  blood  protein,  either  serum  albumen  or 
serum  globulin,  and  that  this  blood  protein  acts  as  a  common  protein 
food  for  all  the  different  cells  of  the  body.  It  is  difficult  to  bring 
any  experimental  proof  for  this  view.  It  is,  however,  practically 
certain  that  a  considerable  proportion  of  the  protein  and  of  its  crystal- 
line products  is  broken  up  still  further  in  the  mucous  membrane. 
All  observers  who  have  investigated  the  point  concur  in  the  state- 
ment that  the  portal  blood  contains  more  ammonia  than  does  the 
blood  of  the  arterial  system,  and  it  seems  probable  that,  as  suggested 


THE  ABSORPTION  OF  THE  FOOD-STUFFS  847 

by  Leathes  and  Folin,  a  large  proportion  of  the  aniino-acids  undergo 
deamination  in  the  wall  of  the  gut,  so  that  the  products  that  are 
actually  absorbed  are  ammonia  and  a  fatty  acid  or  its  oxy-derivative. 
The  ammonia  passes  through  the  liver  and  is  at  once  converted  into 
urea,  so  that  the  post-prandial  rise  in  urea  excretion  is  due  to  this 
immediate  deamination  of  the  ingested  protein.  What  happens 
to  the  non- nitrogenous  moiety  of  the  protein  Ave  do  not  know.  It  is 
apparently  oxidised  fairly  rapidly,  since  excessive  protein  ingestion 
does  not  give  rise  to  any  formation  of  fat,  but  produces  in  every 
case  an  increase  in  the  respiratory  exchanges  and  in  the  output  of 
COg.  At  the  present  time  it  is  impossible  to  decide  with  any  certainty 
as  to  which  of  these  views  of  the  fate  of  the  ingested  protein  is  correct. 
It  is  possible  that  all  three  processes  may  take  place,  viz.  that  a 
proportion  of  the  protein  may  be  built  up  in  the  cells  hning  the 
alimentary  canal  to  form  blood  protein,  so  that  this  organ  would 
have  to  be  regarded  as  an  important  blood-forming  organ,  and  that 
another  portion,  representing  the  amount  required  to  replace  the 
tissue  waste  of  the  body,  is  absorbed  into  the  blood  stream  as  amino- 
acids,  in  which  form  it  is  carried  to  the  tissues  and  reintegrated 
into  the  protein  characteristic  of  each  tissue.  A  third  portion, 
probably  the  major  part  of  the  protein,  does  not  reach  the  tissues 
at  all  as  a  nitrogenous  compound,  but  undergoes  deamination 
in  the  intestinal  wall,  the  nitrogen  being  rapidly  carried  to  the  liver 
and  converted  into  urea,  and  then  excreted  by  the  kidneys,  while 
the  non- nitrogenous  moiety  is  carried  to  the  tissues,  to  which  it  serves 
as  a  ready  and  important  source  of  energy.  Further  investigation  on 
all  these  points  is  required. 

THE  ACTUAL  COURSE  OF  DIGESTION 

In  a  recent  series  of  papers  London  describes  the  course  of  digestion 
of  meals  of  various  characters  in  dogs  which  had  been  provided 
with  fistulse  in  one  of  the  followang  places  :  (a)  gastric  fistula  (into 
the  fundus  of  the  stomach) ;  (6)  pyloric  fistula  (on  the  duodenal  side 
of  the  pylorus) ;  {c)  duodenal  fistula  (about  one  foot  below  the  pylorus) ; 
[d)  jejunal  fistula  (about  the  middle  of  the  small  intestine) ;  (e)  ileum 
fistula  (just  above  the  caecum). 

We  may  take  as  an  example  the  course  of  digestion  of  a  meal 
composed  of  200  grm.  of  bread.  This  is  eaten  by  the  animal, 
mixed  with  saUva  and  swallowed.  On  arriving  at  the  stomach  it 
gives  rise  to  the  secretion  of  gastric  juice.  In  a  series  of  special 
experiments  London  found  that  on  the  average  200  grm.  of  bread 
evoked  the  secretion  of  20  grm.  of  saliva,  about  10  grm.  of  nmcus 
from  the  coats  of  the  stomach,  and  about  315  grm.  of  gastric  juice. 
The  secretion  of  gastric  juice  is  continuous  during  the  whole  time 


848 


PHYSIOLOGY 


that  the  food  remains  in  the  stomach.  In  the  animal  with  a  pyloric 
fistula,  one  to  two  minutes  after  the  meal  had  been  taken,  a  few 
drops  of  alkaline  fluid  were  extruded  from  the  opening.  From  three 
to  eight  minutes  after  the  conclusion  of  the  meal  small  quantities 
of  clear  acid  gastric  juice  were  repeatedly  extruded.  The  first  ad- 
mixture of  the  food  wdth  the  outflow  from  the  fistula  occurred  at  eight 
to  twelve  minutes  after  the  completion  of  the  meal,  and  after  this 
time  the  pylorus  continued  to  open  at  regular  intervals  of  ten  to 
forty  seconds,  discharging  each  time  a  small  amount  of  fluid  com- 
posed of  particles  of  undigested  bread  mixed  with  gastric  juice. 
One  and  a  half  hours  later  the  pylorus  began  to  open  less  regTilarly 
and  the  fluid  became  of  a  more  pasty  consistence,  devoid  of  lumps 
of  undigested  bread.  In  the  fourth,  fiith,  and  sixth  hours  after  the 
meal  the  pylorus  opened  only  once  every  one  or  two  minutes,  and 
towards  the  end  of  this  period  the  fluid  extruded  was  clear.  The 
following  Table  shows  the  percentage  amount  of  food  taken  which 
had  left  the  stomach  at  the  end  of  each  hour  after  the  meal : 


First'hour  . 

.     32-6     per 

Second  hour 

.     17-9 

Third  hour . 

.     29-5 

Fourth  hour 

.       1-87 

Fifth  hour  . 

.       6-66 

Sixth  hour  . 

.       4-21 

The  large  proportion  of  the  ingested  food  leaving  the  stomach 
during  the  first  two  or  three  hours  can  hardly  be  regarded  as  normal. 
Since  in  these  experiments  there  was  a  free  outflow  from  the 
pylorus  and  the  food  was  not  allowed  to  enter  the  duodenum,  the 
local  reflex,  evoked  by  the  presence  of  acid  in  the  duodenum,  was 
absent.  The  gastric  contents  obtained  in  this  way  were  analysed  in 
order  to  find  what  changes  had  been  wrought  on  the  food  by  the 
gastric  juice.  It  was  found  that  32  per  cent,  of  the  bread  had  been 
brought  into  solution.  This  solution  had  afiected  the  proteins  more 
than  the  carbohydrates.  Thus  67  per  cent,  of  the  nitrogen  had  been 
brought  into  soluble  form,  consisting  chiefly  of  albumoses  and  peptones. 
No  amino-acids  were  formed.  Only  25  per  cent,  of  the  starch  of  the 
bread  had  been  rendered  soluble,  and  of  this,  21  per  cent,  was  in 
the  form  of  dextrine  and  4  per  cent,  in  the  form  of  sugar.  No 
absorption,  however,  either  of  the  digested  proteins  or  of  the  digested 
carbohydrates  was  ever  found  to  take  place  in  the  stomach. 

DUODENAL  DIGESTION.  The  influence  exerted  by  the  pan- 
creatic juice,  bile,  and  succus  entericus,  poured  out  on  the  food 
in  the  duodenum,  was  studied  by  analysis  of  the  intestinal  contents 
leaving  the  intestine  by  a  fistula,  either  at  the  lower  end  of  the  duo- 
denum, or  in  the  jejunum,  or  in  the  ileum.    From  the  duodenal 


THE  ABSORPTION  OF  THE  FOOD- STUFFS  849 

fistula  the  expulsion  of  food  occurs  at  repeated  intervals,  but  in  a 
somewhat  irregular  fashion,  its  movements  being  determined  partly 
by  the  contractions  of  the  stomach  and  partly  by  those  of  the  duo- 
denal wall.  Usually  a  large  gush  is  followed  by  a  series  of  small  gushes. 
Although  only  a  foot  intervenes  between  the  duodenal  fistula  and 
the  pyloric  fistula,  a  great  difference  is  observed  in  the  character  of 
the  intestinal  contents  obtained  in  the  two  cases.  The  outflow  from 
the  duodenum,  being  mixed  with  the  pancreatic  juice  and  the  bile, 
is  yellow  in  colour  and  increased  in  amount.  With  a  meal  of  200  grm. 
there  is  secreted  on  the  average  130  grm.  ol  bile  and  1 40  grm.  of  pancreatic 
juice.  During  its  passage  through  the  duodenum  the  carbohydrates 
of  the  food  undergo  considerable  changes,  so  that  even  one  foot 
below  the  pylorus  we  find  that  one-half  to  three-fifths  of  the  carbo- 
hydrates have  been  converted  into  dextrine  and  sugar.  A  further 
digestion  of  the  proteins  also  takes  place  amounting  to  about  one- 
tenth  of  the  whole  protein  taken  with  the  food. 

On  deducting  Ihe  amount  of  juices  which  have  been  added  to 
the  food  it  is  found  that  even  over  this  short  length  of  intestine  absorp- 
tion has  taken  place  of  about  one-sixth  of  the  ingested  food,  about 
one -fourth  of  the  carbohydrates  having  been  absorbed  and  about 
one-eighth  of  the  proteins. 

In  a  dog  with  a  fistula  about  the  middle  of  its  small  intestine, 
the  outflow  began  six  to  fifteen  minutes  after  the  meal,  and  lasted 
six  or  seven  hours.  The  outflow  was  by  small  gushes  repeated  at 
intervals  of  five  to  ten  seconds  separated  by  intervals  of  one  to  five 
minutes,  during  which  nothing  appeared  at  the  orifice  of  the  cannula. 
The  material  obtained  was  quite  different  in  character  from  that 
flowing  from  the  duodenal  fistula.  The  pasty  character  had  dis- 
appeared, the  material  forming  a  frothy,  orange-yellow,  even  jelly- 
like mass  with  practically  no  trace  of  undigested  bread. 

From  a  fistula  in  the  ileum  the  outflow  occurred  at  long  intervals 
of  three  to  fifteen  minutes  and  was  much  scantier  than  that  obtained 
from  the  jejunal  fistula,  consisting  of  a  thick  jelly-Uke,  orange- 
coloured  mass.  Both  proteins  and  carbohydrates  were  entirely 
digested,  and  in  the  case  of  the  former  the  chief  products  of  digestion 
consisted  of  amino-acids.  Thus  in  one  experiment,  after  four  large 
meals  of  500  grm.  of  meat  each  had  been  given,  in  order  to  obtain 
sufficient  quantity  for  analysis,  175  grm.  of  soluble  substances  were 
obtained.  From  this  were  isolated  tyrosine,  leucine,  alanine,  aspartic 
acid,  lysine,  and  traces  of  arginine  and  histidine. 

From  a  fistula  in  the  caecum  there  was  no  outflow  until  four  or 
five  hours  after  the  meal  had  been  taken.  The  material  from  the  gut 
was  then  extruded  in  fascal-hke  masses  at  long  intervals  of  one  half 
to  one  hour.     This  regular  outflow  lasted  for  about  six  hours.     The 

64 


850 


PHYSIOLOGY 


reaction  of  the  contents  was  strongly  alkaline,  with  no  food  particles, 
and  the  material  contained  merely  debris  of  cells,  with  small  traces 
of  sugar,  dextrin,  and  unaltered  starch.  The  absorption  of  the 
food-stuffs  is  thus  practically  complete  by  the  time  that  the  food 
has  reached  the  lower  end  of  the  small  intestine. 

The  following  Table  gives  the  total  amounts  obtained  in  a  series 
of  experiments  from  the  different  fistvdae  after  administration  of 
200  grm.  of  bread,  and  also  the  percentage  amount  of  food-stuffs 
which  had  been  absorbed  before  the  food  had  arrived  at  the  level 
of  the  fistula  in  question  : 


Total  amounts 

obta 

ined 

Absorbed 

from  200  grm. 

of  b 

read 

per  cent. 

Pyloric  fistula 

691  grm. 

0 

Duodenal  fistula. 

691  „ 

17-45 

Jejunal  fistula      . 

585  „ 

37-77 

Ileum  fistula 

412  „ 

67-65 

Csecal  fistula 

80  „ 

94-34 

SECTION  X 

THE    FiECES 

The  faeces  are  often  regarded  as  representing  the  nndigested  or 
indigestible  constituents  of  the  food  which  have  escaped  sohition 
and  absorption  in  their  passage  through  the  ahmentary  canal.  This 
view  is  hardly  correct  as  applied  to  man  or  to  the  carnivora.  In  these 
the  absorption  of  the  constituents  of  a  meal,  whether  consisting 
of  fats,  proteins,  or  carbohydrates,  is  practically  complete  by  the 
time  that  the  food  has  arrived  at  the  lower  end  of  the  ileum.  The 
faeces,  in  fact,  are  not  derived  from  the  food,  but  are  produced  in 
the  ahmentary  canal  itself.  This  is  shown  by  the  fact  that  on 
analysing  the  faeces  no  soluble  carbohydrates  or  proteins,  albumoses, 
peptones,  or  amino-acids  are  to  be  found.  After  a  meal  of  meat 
microscopic  examination  of  the  faeces  reveals  no  trace  of  striated 
muscle  fibres.  Moreover  animals  in  a  state  of  complete  starvation 
form  faeces  which  do  not  differ  in  their  composition  from  the  faeces 
which  are  found  after  feeding  with  meat,  eggs,  sugar,  or  cooked 
starch,  though  the  amoimt  is  less  in  a  state  of  inanition  than  under 
normal  circumstances.  In  one  experiment  Hermann  isolated  a 
loop  of  g-ut,  joining  its  ends  together  so  that  a  continuous  ring  was 
formed.  The  continuity  of  the  gut  was  then  restored  by  suturing 
the  two  free  ends.  After  some  weeks  the  isolated  loop  was  found 
to  contain  a  semi-solid  material  similar  to  faeces  in  appearance,  con- 
sistence, and  chemical  composition.  It  contained  a  large  amount 
of  phosphoric  acid,  lime,  and  iron. 

So  long  as  vegetables  or  coarsely  ground  cereals  are  excluded 
from  the  diet,  the  nature  of  the  latter  does  not  alter  the  chemical 
constitution  or  appearance  of  the  faeces.  Under  these  circmnstances 
the  faices  have  the  following  composition  : 

Water 65  to  fi?  \wv  m-nt. 

Nitrogen    .  .  .  .  .  5  to    9       ,, 

Etiier  extract     .  .  .  .  12  to  18       „ 

Ash 11  to -22       „ 

The  ash  consists  chiefly  of  hme  and  phosphoric  acid  with  some 
iron  and  magnesia.  The  ethereal  extract  contains  fatty  acids  and 
a  small  amount  of  lecithin.  Neutral  fat  is  present  in  very  small 
proportions.    The  faeces  also  contain  small  quantities  of  cholalic  acid 

851 


852 


PHYSIOLOGY 


and  its  products  of  decomposition,  dyslysin,  and  coprosterin,  a 
body  allied  to  cholesterin,  and  a  certain  amount  of  purine  bases 
consisting  of  guanine,  adenine,  xanthine,  and  hypoxanthine.  On 
the  average  the  fseces  contain  about  0-11  gxm.  of  purine  bases  per 
diem,  about  seven  times  as  much  as  is  contained  in  the  urine  passed 
in  the  same  time.  The  material  basis  of  the  faeces  seems  to  be  largely 
desquamated  epithehal  cells  from  the  intestinal  wall,  and  bacteria, 
of  which  countless  numbers,  chiefly  dead,  are  present.  It  has  been 
reckoned  that  as  much  as  50  per  cent,  of  the  faeces  may  consist  of 
the  dead  bodies  of  bacteria. 

Very  different  is  the  composition  of  faeces  if  the  food  contains 
a  large  amount  of  cellulose.  Not  only  does  the  ingested  cellulose 
pass  unchanged  into  the  faeces,  but  large  quantities  of  other  substances 
enclosed  in  the  cellulose  walls  may  also  escape  digestion  and  absorp- 
tion. Moreover  the  increased  bulk  of  the  undigested  residue  stimu- 
lates peristalsis,  and  thus  quickens  the  passage  of  the  food  through 
the  gut  to  such  an  extent  that  the  digestive  ferments  have  not  time 
to  exert  their  full  action  on  the  digestible  constituents  of  the  food. 
The  influence  of  the  character  of  the  food  is  well  illustrated  by  a 
comparison  of  the  amount  and  composition  of  the  faeces  on  different 
kinds  of  bread  (Rubner) : 


Kind  of  bread 

Weight  of 
moist  faeces 

Weight  of 
faeces  dried 

Percentage  of 
ingested  food 

Nitrogen 
(gnn.) 

Bread  from  fine  flour     . 
Bread  from  coarse  flour . 
Brown  bread 

132-7 

252-8 
317-8 

24-8 
40-8 
75-79 

4-03 

6-66 

12-23 

2-17 
3-24 
3-80 

The  follo\ving  Table  is  also  instructive.  In  this  Table  Rubner 
calculates  the  amount  of  faeces  which  a  man  would  pass  in  twenty- 
four  hours  if  he  satisfied  his  energy  requirements  at  the  expense 
of  one  only  of  the  different  kinds  of  food  enumerated.  The  numbers 
refer  to  the  amount  of  organic  material  which  would  be  excreted 
in  the  faeces  : 


Meat    . 

.     26  grm. 

Rice 

50  grm 

Eggs    . 

.     26     „ 

Maize 

51      „ 

Macaroni 

.     27     „ 

Turnips 

101      „ 

Wheaten  bread 

.     36     „ 

Potatoes    . 

133      „ 

Milk     . 

.     42     „ 

Coarse  broMii  bread 

146      „ 

The  indigestible  cellulose  in  the  food  is  not  without  value.  It 
has  been  shown  previously  that  the  peristaltic  contractions  of  the 
intestine  are  roused  primarily  by  the  mechanical  stimulus  of  dis- 
tension.    If  the  food  is  capable  of  entire  digestion  and  absorption 


THE  F^OES  85.3 

the  amount  of  faeces  formed  is  limited  to  that  produced  by  the 
intestinal  wall  itself.  The  small  bulk  exercises  very  little  stimulating 
effect  on  the  intestine,  and  the  movements  of  the  latter  will  therefore 
tend  to  be  sluggish,  especially  in  the  absence  of  the  mechanical 
stimulus  determined  by  muscular  exercise.  The  presence  of  a  certain 
amount  of  cellulose  in  the  diet  may  therefore  be  of  considerable 
advantage  by  giving  bulk  to  the  faeces  and  ensuring  the  proper 
regular  evacuation  of  the  lower  gut.  It  is  probable  that  the  con- 
stipation which  is  so  common  a  disorder  in  civihsed  communities 
is  due  as  much  to  the  refinement  in  the  preparation  of  the  food  as 
to  the  prevalence  of  sedentary  occupations  incident  on  the  working 
of  such  a  community. 


CHAPTER  XI 
THE  HISTORY  OF  THE  FOOD-STUFFS 

SECTION  I 

PROTEIN  METABOLISM 

A  PROTEIN  consists  of  the  elements  carbon,  hydrogen,  oxygen, 
nitrogen,  and  sulphur.  In  the  oxidation  which  these  bodies,  in 
common  with  the  other  food-stuffs,  undergo  in  the  body,  the  carbon 
and  hydrogen  are  converted  to  carbon  dioxide  and  water.  A  certain 
proportion  escapes  this  complete  oxidation,  being  excreted  by  the 
kidneys  in  combination  with  nitrogen  as  the  essential  constituents 
of  the  urine  (chiefly  urea).  When  proteins  are  oxidised  in  the  body 
there  is  a  definite  relation  between  the  carbon  dioxide  which  is  pro- 

CO 

duced    and    the    oxygen    consumed.     This   respiratory   quotient  ^ 

O2 

in  the  case  of  proteins  equals  0-81.  Since  the  respiratory  quotient  on 
a  pure  consumption  of  fats  is  only  0-71  and  on  carbohydrates  equals  1, 
we  may,  by  a  study  of  the  respiratory  exchanges,  arrive  at  some  idea 
of  the  extent  to  which  protein  metabolism  is  responsible  for  the 
energy  exchanges  of  the  body  as  a  whole.  Such  information  by 
itself  will  always  be  somewhat  uncertain,  since  it  is  possible,  by  a 
combination  of  fat  and  carbohydrate  metabolism  in  proper  propor- 
tions, to  produce  a  respiratory  quotient  identical  ^^^th  that  obtaining 
when  the  metabolism  is  purely  of  protein.  On  the  other  hand,  the 
specific  constituents  of  proteins,  namely,  nitrogen  and  sulphur,  are 
excreted  entirely  by  the  urine  (if  we  exclude  the  small  traces  which 
may  leave  the  body  in  the  sweat;  or  as  scales  of  epidermis,  hair,  nails, 
&c.).  It  has  therefore  been  customary  to  take  the  nitrogen  output 
in  the  urine  as  an  index  of  the  protein  metabolism.  This  proceeding 
is  only  justified  if  we  remember  that  we  are  deaUng  in  the  urine 
merely  with  the  nitrogen  and  sulphur  of  the  protein  molecule,  and 
that  a  large  proportion  of  the  carbon  and  hydrogen  moiety  of  this 
molecule  is  being  left  unregarded. 

Since  we  cannot  follow  all  the  stages  in  the  changes  undergone 
by  proteins  on  their  way  through  the  body,  it  will  be  convenient  to 
take  the  nitrogenous  end-products  of    protein  metaboUsm  such  as 

854 


PROTEIN  METABOLISM 


855 


appear  in  the  urine,  and  to  determine,  where  possible,  their  pre- 
cursors, and  the  conditions  which  determine  their  formation  in  the 
body.  The  chief  nitrogenous  constituents  of  urine  are  urea,  ammonia, 
uric  acid,  creatinine,  hippuric  acid.  There  is  a  small  residue  of 
undetermined  nitrogen  which  may  include  traces  of  purine  bases, 
such  as  xanthine  and  hypoxanthine,  traces  of  amino-acids,  small 
amounts  of  pigment  and  of  nucleo-protein  from  the  wall  of  the 
bladder.  The  relative  proportions  in  which  these  bodies  occur  are 
not  invariable,  but  differ  according  to  the  nature  of  the  protein  foods 
taken  and  also  according  to  the  proportion  which  the  protein  meta- 
bolism bears  towards  the  total  energy  requirements  of  the  body.  In 
the  following  Tables  (Folin)  are  given  the  average  composition  of  two 
specimens  of  urine  from  the  same  individual,  one  on  a  diet  containing 
the  ordinary  proportion  of  protein,  and  the  other  on  a  diet  containing 
only  a  minimal  amomit  of  this  food-stuff  : 


TABLES  I  AND  II 
Distribution  of  Nitrogen  in  Urine  on  Various  Diets 


July  13 

July  20 

Ordinary  diet 

Low  proteiu  di' i 

Vol.  of  urino   . 

1170  c.c. 

385  O.C. 

Total  nitrogen 

16-8  grm. 

3-60  grm. 

Urea 

14-70  grm.  =  87-5  % 

2-20  grm.  =  61-7% 

Ammonia 

0-49  grm.  =     3-0  % 

0-42  grm.  =  11-3% 

Uric  acid 

0-18  grm.  =     M  % 

0-09  grm.  =    2-5  % 

Creatinine 

0-58  grm.  =     3-6  % 

0-60  grm.  =  17-2  % 

Undetermined 

0-85  grm.  =    4-9  % 

0-27  grm.  =    7-3  % 

Total  SO3 

3-64  grm. 

0-76  grm. 

Inorganic  SO;j 

3-27  grm.  =  90-0  % 

0-46  grm.  =  60 -.5  % 

Ethereal  SO3  . 

0-19  grm.  =     5-2  % 

0-10  grm.  =  13-2  % 

X(>utral  S 

0-18  grm.  =     4-8  % 

0-20  grm.  =  26-3  o^ 

In  dealing  with  the  metabolism  of  the  body  as  a  whole  we  saw 
reason  to  believe  that  the  proteins  taken  in  with  the  food  might  be 
regarded  as  having  a  twofold  destiny.  One  part,  and  under  normal 
circumstances  the  greater  part,  is  applied  to  the  production  of  energy 
in  the  body,  in  this  respect  discharging  a  function  which  might 
equally  well  be  performed  by  the  fats  and  carbohydrates  of  the  food. 
In  its  second  function  protein  cannot  be  replaced  by  any  other  food- 
stuff, since  it  alone  contains  the  necessary  elements  as  well  as  the 
groupings  of  these  elements  which  are  essential  for  the  building  up  of 
the  living  tissues.  We  saw  reason  to  believe  that  this  tissue  meta- 
bolism only  accounted,  however,  for  a  small  part  of  the  nitrogen  of 
the  food.     On  this  account  it  is  possible  to  ensure  health  and    a 


856  PHYSIOLOGY 

condition  of  nitrogenous  equilibrium  with  amounts  of  protein  in  the 
diet  of  man  which  might  vary  between  40  and  200  grm,  per  diem. 
The  more  protein  that  is  taken  in  wnth  the  food  the  greater  is  the 
relative  amount  which  is  apphed  to  the  energy  needs  of  the  body. 
If  therefore  we  would  attempt  to  find  out  what  are  the  end-products 
of  the  tissue  metabolism  we  should  confine  the  energy  metabolism  of 
proteins  within  the  smallest  possible  limits  by  reducing  the  quota  of 
protein  in  the  diet  to  its  minimum.  Folin  has  shown  that  if  we 
compare  the  composition  of  the  urine  obtained  under  these  two 
conditions,  namely,  on  a  diet  containing  a  normal  quantity  of  protein 
and  on  a  diet  containing  a  minimal  amount,  we  find  evidence  of  a 
qualitative  difference  between  the  two  kinds  of  metabolism.  The 
difierence  is  well  brought  out  in  the  tables  just  quoted.  On  a  large 
diet  the  greater  part  of  the  nitrogen  can  be  regarded  as  derived 
directly  from  the  food,  whereas  on  a  small  diet  a  relatively  larger 
proportion  of  it  must  come  from  protein  which  has  been  previously 
built  up  into  the  tissues.  Folin  distinguishes  these  two  sources  of  the 
nitrogen  of  the  urine  as  exogenous,  i.e.  that  from  the  food,  and  endo- 
genous, i.e.  derived  from  the  tissues.  Two  facts  stand  out  in  comparing 
these  two  urinary  analyses.  In  the  first  place,  on  a  normal  protein  diet 
the  urea  accounts  for  87  per  cent,  of  the  total  nitrogen  of  the  urine.  On 
an  excessive  protein  diet  this  percentage  may  rise  to  90  or  95.  On 
the  low  protein  diet  the  percentage  of  nitrogen  appearing  as  urea  is 
reduced  to  60.  On  the  other  hand,  practically  identical  amounts  of 
creatinin  are  obtained  under  the  two  conditions,  so  that  whereas  on 
the  full  diet  it  amounts  only  to  3-6  per  cent.,  on  the  low  protein  diet 
it  forms  as  much  as  17  per  cent,  of  the  total  nitrogen  output.  We 
are  therefore  justified  in  regarding  urea  as  to  a  large  extent  exogenous 
in  origin,  and  as  derived  directly  from  the  nitrogenous  moiety  of  the 
protein  molecule,  which  may  not  at  any  time  have  formed  part  of  the 
living  tissues  of  the  body. 

On  giving  a  large  protein  meal  to  a  dog  the  urea  in  the  urine 
rapidly  rises,  and  at  the  end  of  four  or  five  hours  50  per  cent,  of  the 
total  nitrogen  taken  in  with  the  food  has  appeared  in  the  urine  as  urea 
(Fig.  351).  If  we  take  into  account  that  the  digestion  of  a  meat  meal  in 
this  animal  may  go  on  for  eight  hours,  we  are  justified  in  the  statement 
that  by  far  the  greater  portion  of  the  protein  nitrogen  taken  vnth.  the 
food  is  excreted  almost  directly  after  absorption  as  urea  in  the  urine. 
Urea  is  therefore  to  be  regarded  in  the  first  place  as  an  index  to  the 
amount  of  protein  absorbed.  We  have  seen  that  the  end-products  of 
protein  digestion  in  the  intestine  are  the  amino-acids  ;  and  that  these 
are  the  immediate  precursors  of  the  urea  is  shown  by  the  fact  that 
the  administration  of  these  bodies  is  followed  very  rapidly  by  the 
appearance  of  the  whole  of  their  nitrogen  in  the  urine  as  urea.     Many 


PROTEIN  METABOLISM 


857 


attempts  have  been  made  to  explain  the  method  by  which  urea  may 
be  derived  from  the  aniino-acids. 

F.  Hofnieister  succeeded  in  preparing  urea  by  oxidising  amino- 
acids  with  potassium  permanganate  in  the  presence  of  ammonia  and 
ammonium  sulphate.  He  assumes  that  urea  is  formed  by  an  oxida- 
tion synthesis.  The  first  step  would  be  the  formation,  by  oxidati(ui 
5c 


0 


\ 

--x^ 

\ 

"""■ 

--. 

\ 

\ 

\ 

^ 

K:;;- 

-- 

\ 

-^ 

■^■^ 

"^-^ 

— 

-.^_ 

~~^"^ 

1         . 

— .--. 

— ■ 

rr— 

... 



'                   i 

1 

0 


12  16 


20 


4 
5 

24H0L 


Fig.  351.  The  hourly  variation  in  the  excretion  of  nitrogen  after  a  meal. 
The  meal  was  given  at  0.  The  thick  line  represents  the  average 
absorption  of  the  food  from  the  alimentary  canal.  The  thin-lined 
curves  represent  the  N.  excretion  (1)  after  a  meal  of  1000  grm.  meat  ; 
(2)  after  500  grm.  meat  and  150  grm.  fat ;  (3)  after  a  meal  of  500  grm. 
meat :  (4)  and  (5)  both  represent  the  excretion  in  a  fasting  animal. 
(From  TiGEKSTEDT  after  Feder.) 

of  protein  or  amino-acids,  of  the  group  CONTI2,  and  this  at  the  moment 
of  formation  would  combine  witb.  the  NH,  left  over  in  the  oxidation 

of  the  ammonia  to  form  urea.  COv 

According  to  Drechsel  and  Nencki,  the  immediate  precursor  of  the 
urea  is  probably  ammonium  carbamate,  which  loses  a  molecule  of 
water,  thus  : 

/ONH4  .NH., 

C0<^  -  H.,0  =  CO^ 

Schroder,  on  the  other  hand,  suggested  that  the  urea  was  formed 
from  ammonium  carbonate  by  the  loss  of  two  molecules  of  water. 


CO 


/ 


ONH, 


-  2H,0  =  CO 


ONH. 


.NH, 
^NHa 


858  PHYSIOLOGY 

In  all  these  views  it  is  assumed  that  before  urea  can  make  its  appear- 
ance in  the  urine  there  must  be  a  complete  destruction  of  the  amino- 
acid.  If  we  compare  the  structure  of  any  amino-acid  with  that  of  urea 
we  see  that  the  proportion  of  carbon  to  nitrogen  is  very  much  greater 
in  the  former  than  in  the  latter,  and  that  even  after  splitting  off  from 
two  molecules  of  amino-acid  the  necessary  elements  to  form  urea, 
CON2H4,  almost  the  whole  of  the  molecule  will  be  left  in  an 
unoxidised  condition.  A  complete  oxidation  of  the  amino-acid  would 
result  in  the  production  of  ammonia,  carbon  dioxide,  and  water,  so 
that  if  oxidation  were  the  method  adopted  for  the  production  of  urea 
the  immediate  precursor  of  this  substance  would  be  a  combination 
of  ammonia  and  carbonic  acid,  either  ammonium  carbonate  as 
suggested  by  Schroder,  or  carbamate  as  thought  by  Dreschel.  We 
have  distinct  evidence  that  ammonia  in  one  of  these  two  forms  is 
an  important  precursor  of  urea.  If  ammonium  carbonate  or  carba- 
mate be  administered  to  man  or  to  an  animal  the  whole  of  it  is  turned 
out  in  the  urine  as  urea.  Although  there  is  normally  a  small  amount 
of  ammonia  in  the  urine,  it  is  not  increased  by  injections  of  ammonium 
carbonate.  Schroder  has  shown  that  the  liver,  even  after  removal 
from  the  body,  has  the  power  of  transforming  ammonium  carbonate 
into  urea.  Defibrinated  blood  mixed  with  ammonium  carbonate  was 
passed  through  a  surviving  liver.  After  a  little  time  it  was  found 
that  the  ammonium  carbonate  had  disappeared  and  that  its  place 
was  taken  by  urea.  If  the  liver  is  necessary  for  this  conversion  to 
take  place  and  ammonia  is  a  constant  precursor  of  urea,  we  should 
expect  to  find  that  the  abolition  of  the  hepatic  functions  would  cause 
the  appearance  in  the  urine  of  ammonium  carbonate  or  carbamate 
in  the  place  of  urea.  The  cutting  out  of  the  Hver  is  not,  however, 
an  easy  matter  in  mammals.  Ligature  of  the  portal  vein,  which 
would  be  a  necessary  step  in  the  extirpation  of  the  liver,  causes  the 
blood  to  be  dammed  up  behind  the  ligature  in  the  portal  area.  The 
intestinal  wall  gets  full  of  efEused  blood,  the  blood  pressure  falls 
steadily,  and  the  animal  dies  within  a  few  hours,  being  bled  to  death, 
so  to  speak,  into  its  portal  vessels.  A  way  of  obviating  this  difficulty 
was  suggested  by  a  Russian  surgeon,  Eck,  and  was  successfully  carried 
out  by  Pawlow.  Before  ligature  of  the  portal  vein,  this  vessel  was 
joined  to  the  vena  cava  and  an  artificial  opening  made  connecting  the 
lumen  of  the  two  vessels,  so  that,  after  the  ligature,  the  blood  could 
flow  directly  into  the  general  circulation  without  passing  through  the 
liver.  Some  animals  operated  on  in  this  way  showed  no  abnormal 
symptoms  whatsoever.  There  was  a  rapid  formation  of  a  collateral 
circidation  so  that  the  blood  could  get  round  the  ligature  to  the  liver. 
Lender  all  circumstances  a  path  to  the  liver  was  still  open  by  the 
hepatic  artery,  but  to  arrive  here  the  blood  from  the  alimentary 


PROTEIN  METABOLISM  859 

caiiiil  li;i(l  liist  lo  |)u,s,s  tlif()uj,4i  the  general  circulation.  A  certain 
number  of  animals  were  found  to  be  particularly  susceptible  to  the 
nature  of  their  diet.  On  a  diet  largely  consisting  of  carbohydrates 
they  maintained  good  health.  After  a  large  meat  meal,  however,  they 
became  ill,  and  in  many  cases  suffered  from  tremors  and  convulsions 
ending  iii  coma.  At  the  same  time  there  was  a  definite  increase  of 
ammonia  in  the  urine,  chiefly  in  the  form  of  ammonium  carbamate. 
Analysis  of  the  blood  from  a  normal  animal  shows  that  during  protein 
digestion  there  is  a  constant  excess  of  ammonia  in  the  blood  of  the 
portal  vein  above  that  in  any  other  part  of  the  vascular  system.  In 
the  carotid  blood  the  normal  amount,  according  to  Nencki,  is  about 
2  mg.  per  100  c.c  in  the  portal  blood  4  to  6  mg.  During  the 
morbid  symptoms  brought  on  by  a  protein  meal  in  the  animals  in 
whom  an  Eck  fistula  has  been  produced,  the  ammonia  in  the  carotid 
blood  may  rise  to  as  much  as  4  mg.,  i.e.  to  the  amount  normally 
found  in  portal  blood.  Pawlow  and  Nencki  therefore  ascribed  the 
symptoms  observed  in  these  dogs  after  a  heavy  meat  meal  to  a  condi- 
tion of  '  ammoniajmia,'  and  regarded  the  liver  as  an  organ  which  is 
normally  concerned  in  protecting  the  rest  of  the  body  from  ammonia 
produced  in  the  alimentary  tract  by  converting  this  substance  into 
the  innocuous  neutral  body,  urea. 

This  view  of  the  function  of  the  liver  is  confirmed  by  Schroder's 
experiments  on  birds.  In  these  animals  the  chief  nitrogenous  excretion 
is  not  urea,  but  ammonium  urate,  60  per  cent,  of  the  nitrogen  of  the 
urine  appearing  in  the  form  of  uric  acid.  In  birds  there  is  naturally 
a  communication  between  the  portal  system  and  the  general  venous 
system  by  means  of  the  vein  of  Jacobson,  which  connects  the  lower 
branches  of  the  portal  vein  with,  as  a  rule,  the  left  renal  vein  (Fig.  352). 
On  this  account  the  liver  can  be  cut  out  of  the  body  or  of  the  circu- 
lation without  entailing  the  rapid  death  of  the  bird,  which  may  live 
for  three  or  four  days,  and  pass  urine  after  the  operation.  The  urine 
s,  however,  fluid,  and  the  uric  acid,  instead  of  accounting  for 
60  per  cent,  of  the  total  nitrogen,  now  forms  only  5  per  cent. 
The  place  of  the  greater  part  of  the  uric  acid  has  been  taken 
by  ammonium  lactate,  which  therefore  seems  to  be  the  chief 
immediate  precursor  of  the  uric  acid  in  the  urine  of  birds.  We 
shall  have  occasion  to  consider  the  method  of  transformation  of 
ammonium  lactate  to  uric  acid  more  fully  when  dealing  with  the  origin 
of  the  latter  body. 

Of  late  years  evidence  has  been  brought  forward  that  the  fornui- 
tion  of  ammonia  from  the  amino-acids  may  involve  no  such  profound 
changes  of  oxidative  disintegration  as  were  suggested  in  the  theories 
of  Hofmeister  or  Schroder.  If  amino-acids  be  treated  with  the  pulp 
of  .various  organs  the  amount  of  ammonia  in  the  mixture  is  increased, 


860 


-.  PHYSIOLOGY 


an  increase  which  is  absent  when  no  amino-acids  are  added.  More 
ammonia,  for  instance,  was  found  when  leucine,  glycine,  tyrosine,  or 
cystine  was  added  to  the  pulp.  On  the  other  hand,  phenylalanine 
gave  rise  to  no  production  of  ammonia.  This  conversion  was  ascribed 
by  Lang  to  the  presence  of  a  deaminising  ferment  in  the  cells  of 
these  different  tissues,  and  Leathes  and  Folin  have  suggested  that 
this  process  of  deami nation  is  the  essential  factor  in  the  production  of 
the  excess  of  ammonia  in  the  portal  blood  and  in  the  rapid  conversion 
of  the  nitrogen  of  the  ingested  protein  into  urea.     Viewed  in  this 


jl^-lnf.  Vena  Cava 


Portal  V. 


v.  of  Jacobson 
Inf.  mes.v 

Caudal  v 


Rectum 


Fig.  352.      Diagram  to  show  the  arrangement  of  the  veins  in  the  bird, 
mth    the    communication    of   the    renal   and    portal    veins.     (After 

MORAT.) 


light,  these  results  of  Lang,  Nencki,  and  others  effect  an  entire 
revolution  in  our  views  of  protein  metabolism.  Instead  of  regard- 
ing the  urea  which  appears  in  the  urine  after  protein  ingestion 
as  produced  by  the  total  disintegration  of  the  protein  molecule, 
we  see  now  that  it  represents  merely  the  throwing  off  of  the  nitro- 
genous part  of  this  molecule.  This  deamination  may  be  a  purely 
hydrolytic  change  or  it  may  be  associated  with  oxidation  or  reduction. 
Deaminisation  of  alanine,  for  instance,  by  simple  hydrolysis  would 
result  in  the  formation  of  lactic  acid  (an  oxy-fatty  acid). 


CH. 


OH. 


OH.NH2  +  H2O  =  NH3  -f  (JHOH 

I  I 

COOH  COOH 


PROTEIN  METABOLISM  861 

If  the  deaniination  were  accompanied  with  oxidation  the  corresponding 
keto-fatty  acid  would  be  formed,  thus 

CH3.CHNH2.COOH  +  0  =  NH3  +  CH3.CO.COOH. 

If  reduction  took  place  at  the  same  time,  the  result  would  be  the 
production  of  a  saturated  fatty  acid.  Knoop  has  shown  that  all 
three  cases  may  occur.  The  investigation  of  the  stages  in  deaniination, 
and  indeed  in  the  disintegration  of  fatty  derivatives  generally,  is 
rendered  difficult  by  the  fact  that  all  the  intermediate  products 
undergo  further  change  and  leave  the  body  in  a  state  of  complete 
oxidation,  as  carbon  dioxide  and  water.  If,  however,  an  amino-acid 
group  be  administered  as  part  of  an  aromatic  compound,  i.e.  forming 
a  side-chain  of  the  benzene  ring,  it  is  protected  from  complete  oxida- 
tion by  the  stability  of  this  ring.  The  oxidation  of  the  fatty  side-chain 
may  proceed  to  a  certain  degree,  so  that  intermediate  products  of 
metabolism  may  be  excreted  still  attached  to  the  benzene  nucleus. 
In  the  a-amino-acids  the  point  where  disintegration  first  occurs  is 
the  a-group.  Deamination  Knoop  finds  most,  usually  associated  with 
oxidation.     The  primary  product  is  therefore  an  a-keto-acid.     Further 

oxidation  afEects  the  CO  group,  so  that  carbon  dioxide  is  eliminated 

I  . 

and  the  next  lower  acid  in  the  fatty  acid  series  is  produced.  Thus 
from  alanine  the  body  would  produce  pyruvic  acid,  CH3.CO.COOH, 
and  this  on  further  oxidation  would  form  acetic  acid,  CH3.COOH,  and 
carbon  dioxide.  On  the  other  hand,  these  keto-acids  may  undergo 
reduction  to  an  oxy-acid,  or  even  a  step  further,  to  a  fatty  acid,  though 
the  conditions  which  determine  whether  oxidation  or  reduction  shall 
take  place  have  not  yet  been  fully  studied. 

Of  very  great  importance  is  Knoop's  discovery  that  deamination 
is  a  reversible  process,  so  that,  given  a  right  molecular  grouping,  a 
fatty  acid  residue  may  react  with  ammonia  to  form  an  amino-acid. 
The  proof  of  this  fact  was  facilitated  by  the  discovery  that  the  next 
higher  homologue  of  phenylalanine,  namely,  phenyl-a-amino-butyric 
acid,  when  administered  to  an  animal,  was  excreted  in  large  quanti- 
ties in  the  urine  as  an  ether-soluble  acetyl  derivative,  which  was 
easily  isolated  in  a  state  of  purity.  If  then  this  amino-acid  were 
formed  in  the  body,  one  might  expect  to  find  it  without  difficulty  in 
the  urine.  Knoop  found  that  the  administration  of  either  phenyl- 
a-keto-butyi'ic  acid  or  phenyl-a-oxybutyric  acid  led  to  the  excretion 
of  the  corresponding  amino-acid  in  the  urine.  Since  keto-acids  occvr 
as  the  ordinary  products  of  the  breakdown  of  amino-acids  and  also 
as  the  intermediate  products  of  oxidation  of  oxy-acids,  e.g.  lactic  acid, 
it  is  evident  that  the  animal  body  can  assimilate  ammonia  and  foim 


862  PHYSIOLOGY 

amino-acids,  provided  only  that  it  is  supplied  with  the  proper  non- 
nitrogenous  acids.  These  latter  need  not  be  derived  from  proteins 
at  all,  but,  like  lactic  acid,  be  a  result  of  carbohydrate  metabolism. 
Thus,  if  the  fitting  non-nitrogenous  food  be  given  {e.g.  oxy-fatty  acids, 
or  carbohydrates,  from  which  these  bodies  may  be  formed),  part  of 
the  nitrogen  set  free  by  protein  disintegration  might  be  recombined 
with  the  formation  of  amino-fatty  acids  without  giving  rise  to  urea 
or  appearing  in  any  way  in  the  nitrogen  balance-sheet  of  the  body. 
This  possibility  enjoins  the  necessity  of  caution  in  interpreting  the 
results  of  metabolism  experiments  where  the  nitrogen  excreted  is 
taken  to  represent  the  total  protein  metabolism  of  the  body.  The 
fate  of  the  nitrogen  does  not,  however,  matter  much  to  the  energy 
balance-sheet  of  the  body,  since  so  far  as  regards  energy  the  residue 
of  the  protein  molecule  or  the  amino-acid  molecule  which  is  left 
behind  after  the  process  of  deamination  has  taken  place,has  lost  only 
from  one-fifth  to  one-tenth  of  the  total  energy  of  the  original  molecule. 
This  is  shown  in  the  following  Table  of  the  heat  equivalents  of  some  of 
the  amino-acids  and  their  corresponding  fatty  and  oxy-acids  : 

Calories 
bubstance  pgj.  gj.j^  molecule 

Leucine         ......  855 


Isobutylacetic  acid 
Alanine 
Propionic  acid 
Lactic  acid 
Pyruvic  acid 


837 
389 
367 
329 

not  determined 


Even  in  the  case  of  the  smallest  molecvile  the  loss  of  energy 
attendant  on  simple  deamination  and  conversion  into  the  corresponding 
oxy-acid  only  amounts  to  about  20  per  cent.  We  thus  come  to  the 
conclusion  that  the  urea  output  in  the  urine  after  a  protein  meal  tells 
us  nothing  whatever  about  the  fate  of  that  part  of  the  protein  which 
contains  80  to  90  per  cent,  of  the  total  energy  of  the  protein  food.  So 
far  as  concerns  the  output  of  energy,  the  exogenous  protein  metabolism 
may  be  regarded  as  practically  non-nitrogenous.  The  rise  in  the  rate 
of  excretion  of  urea  after  a  protein  meal  was  regarded  both  by  Voit 
and  Pfliiger  as  a  sign  that  the  cells  of  the  body  preferred  to  use  proteins 
for  all  their  requirements  if  this  substance  were  available.  We  see 
now  that  the  big  output  of  urea  after  a  protein  meal  affords  no  basis 
to  this  view,  but  is  rather  a  sign  that  the  body  has  no  need  for  all  the 
nitrogen  contained  in  its  food  and  that  this  must  be  got  rid  of  before 
the  really  valuable  part,  the  energy-giving  part  of  the  protein  molecule, 
is  admitted  into  the  general  circulation. 

The  important  problem  in  the  energy  metabolism  of  protein  is  thus, 
not  the  origin  of  the  urea,  but  the  nature  of  the  substances  that  are 


PROTEIN  METABOLISM 


863 


left  after  deamination  and  their  subsequent  fate  in  the  body.  Since 
they  contain  onlv  the  elements  carbon,  hydrogen,  oxygen,  one  would 
expect  to  find  that  they  could  replace  either  fat  or  carbohydrate.  So 
far  as  concerns  the  production  of  energy  this  is  true.  Moreover,  as 
we  shall  see  in  dealing  with  the  metabolism  of  carbohydrates,  we  have 
definite  evidence  that  this  non-nitrogenous  moiety  of  the  protein 
molecule  may  be  converted  into  sugar  or  glycogen.  No  experimenter 
has  yet  succeeded  in  bringing  forward  indisputable  evidence  that  fat 
may  be  formed  from  this  part  of  the  protein  molecule  ;  at  any  rate, 
no  fat  which  can  be  stored  in  the  body  and  give  rise  to  the  production 
of  adipose  tissue.  On  the  other  hand,  the  proteins,  more  than  either 
of  the  other  two  food-stuffs,  cause  a  direct  augmentation  of  the  respira- 
tory exchanges  of  the  body.  This  is  shown  in  the  following  Table  by 
Rubner,  in  which  isodynamic  quantities  of  proteins,  fats,  and  carbo- 
hydrates were  administered  during  a  period  of  starvation  : 


Food                                   i 
1 

Calories 

Energy  metabolism 

Day 

X.  grm.            Fat  grm. 

Carboliydrate 
grm. 

\.             body  weight 
calories       ,          i     ■ 
!      calories 

2 
3 
4 
5 
6 
7 
8 

56-8 

167 

411 

1543 
1536 
1446 

969 
1072 
947 
963 
922 
982 
977 

40-2 
44-8 
39-9 
40-9 
39-6 
42-3 
421 

It  will  be  seen  that  the  metabolism,  i.e.  the  caloric  output,  of  the 
body  on  administration  of  protein  increased  11-9  per  cent.,  whereas 
with  fat  the  increase  amounted  only  to  1-2  per  cent.,  and  with  carbo- 
hydrate to  4-7  per  cent.  In  another  similar  experiment  the  animal 
received  574  calories  protein,  54-2  calories  fat,  and  57  calories  carbo- 
hydrate respectively  per  kilo  body  weight.  During  hunger  the  total 
metabolism  per  kilo  body  weight  amounted  to  37'5  calories  ;  with  meat, 
to  46  calories  ;  with  fat,  to  39-4  calories  ;  with  carbohydrates,  to  394 
calories.  Compared  with  the  metabolism  during  starvation  the  rise  per 
cent,  with  protein  was  24-3,  and  Avith  fat  and  carbohydrates  5-1.  This 
surplus  output  of  energy  resulting  from  the  administration  of  protein 
cannot  be  ascribed  to  increased  work  thrown  on  the  digestive  organs. 
There  is  no  evidence  that  this  is  greater  in  the  case  of  proteins  than 
it  would  be  with  carbohydrates  or  fats  ;  and  even  if  the  capacity  of 
these  organs.be  strained  to  their  utmost  bv  administration  of  large 
quantities  of  bones,  the  increase  in  the  carbon  dioxide  output  which 


864  PHYSIOLOGY 

results  is  not  so  great  as  that  following  a  large  protein  meal.  It 
seems  therefore  that  the  CHO  moiety  of  the  protein  undergoes  oxida- 
tion more  rapidly  than  either  dextrose  or  the  ordinary  fats  of  the  diet, 
and  that,  as  we  concluded  in  an  earlier  chapter,  the  metabohsm  of 
these  substances  is  really  to  a  considerable  extent  dependent  on  the 
quantity  presented  to  the  organism  rather  than  on  the  actual  needs 
of  the  cells  of  the  body.  It  is  this  rise  in  metabolism  and  respiratory 
exchanges  after  protein  ingestion  which  justifies  to  a  certain  extent 
the  idea  that  the  proteins,  more  than  any  other  food-stufi,  have  a 
stimulant  action  on  metabolism.  The  reason  why  the  CHO  remainder 
of  the  protein  molecule  is  so  prone  to  oxidation  and  does  not,  like  an 
excess  of  carbohydrates,  undergo  conversion  into  fats  in  the  body,  we 
shall  have  to  consider  in  gTeater  detail  in  dealing  with  the  fate  of 
this  latter  class  of  substances.  We  need,  however,  considerably 
more  evidence  as  to  the  extent  to  which  deamination  occurs 
and  as  to  its  conditions  and  end-products  before  we  can  hope  to 
determine  the  cause  for  the  rapid  breakdown  of  these  end-products 
in  the  body. 

ARE  THE  AMINO- ACIDS  INTERCONVERTIBLE  ? 
Although  the  animal  organism  is  apparently  capable  of  synthetising 
amino-acids  from  ammonia  and  the  corresponding  keto-  or  oxy-fatty 
acid,  it  is  unable  to  convert  one  amino-acid  into  another.  On  this 
account  many  proteins  are  inadequate  as  food  substances  since  they 
do  not  contain  the  necessary  amino-acid  groups.  Life  cannot  be 
supported  on  such  bodies  as  zein  or  gelatin,  which  are  lacking  in  the 
tryptophane  and  tyrosine  groups.  The  failure  in  these  cases  is  not, 
as  has  been  generally  supposed,  owing  to  an  inability  to  assimilate, 
i.e.  synthetise,  nitrogen  as  anmionia,  but  to  the  fact  that  in  the  animal 
the  apparatus  is  wanting  for  the  manufacture  of  some  of  the  oxy-fatty 
acids  and  other  radicals  which  form  the  non-nitrogenous  part  of  the 
amino-acids.  This  view  receives  confirmation  from  the  fact  that  the 
simplest  of  the  fatty  acids,  namely,  glycine,  can  be  easily  manufactured 
in  the  body,  acetic  acid  being  one  of  the  latest  stages  in  the  oxidation 
of  most  carbohydrates  and  fats.  ^  It  is  probable  that  alanine  too  could 
be  easily  manufactured  by  the  body,  but  definite  evidence  on  this 
point  is  not  yet  forthcoming. 

THE  EXCRETION  OF  AMMONIA 
A  large  proportion  of  the  urea  appearing  in  the  urine  after  a 
protein  meal  is  exogenous  and  is  derived  by  a  rapid  separation  of 
ammonia  from  the  proteins  or  their  disintegration  products  almost 
immediately  after  their  absorption.  The  greater  part  of  the  ammonia 
passes  to  the  liver,  and  is  there  converted  into  urea,  which  is  excreted 


PROTEIN  METABOLISM  8(J5 

by  the  kidney.     A  ceitain  small  proportion  of  the  nitrogen  in  the 
urine  is  generally  turned  out  in  the  form  of  ammonia.     This  propor- 
tion is  not  increased  by  the  administration  of  anmionium  carbonate. 
If  ammonimn  chloride  be  given  to  a  starving  rabbit  it  appears  in  the 
urine  unchanged,  and  so  increases  the  proportion  of  anmionia  in  this 
fluid.     If,  however,  the  ammoniiun  chloride  be  administered  at  the 
same  time  as  the  animal  is  receiving  its  ordinary  vegetable  diet  there 
is  no  increase  in  the  ammonia  in  the  urine,  the  whole  of  the  ammonium 
chloride  being  converted  into  urea.     The  factor  which  determines  the 
proportion  of  aromonia  in  the  mine  is  the  relative  proportion  of  acids 
and  bases  which  have  to  be  eliminated  from  the  body.     The  normal 
reaction  of  mine,  though  acid  as  regards  certain  indicators,  can  be 
regarded  as  neutral,  since  it  contains  no  free   hydrogen   ions,   the 
'  acidity '  being  due  to  the  presence  of  such  substances  in  solution  as 
acid  sodium  phosphate.    If  the  fixed  alkalies  in  the  food  are  sufficient 
to  combine  with  the  whole  of  the  acids  excreted  from  the  body,  then 
the  ammonia  will  be  completely  converted  into  urea  and  eliminated  as 
such.  If,  however,  a  dose  of  mineral  acid  be  administered  to  an  animal, 
this  must  be  excreted  in  combination  with  a  base.  If  the  fixed  alkalies 
available  do  not  suffice  for  this  purpose,  the  neutralisation  of  the  acid  is 
effected  by  coupling  with  ammonia.  The  ammonia  of  the  urine  is  there- 
fore an  index  to  the  amount  of  acids  which  are  excreted.    These  acids 
may  be  introduced  directly  with  the  food,  as  when  mineral  acids  are 
administered  by  the  mouth,  or  may  be  the  product  of  abnormal 
metabolic    processes   occurring   in   the   body.     Thus    under   certain 
circumstances,  e.g.  in  complete  carbohydrate  starvation,  there  is  a 
failure  in  the  last  stages  of  the  oxidation  of  fats,  and  oxy-fatty  acids, 
viz.  oxybutyric  acid  and  aceto-acetic  acid,  are  produced  in  the  body 
in  large  quantities,  but  camiot  undergo  further  disintegration.     The 
alkalescence  (electrical  neutrality)  of  the  fluid  media  of  the  body  is  a 
necessary  condition  for  the  continuance  of  the  life  of  the  cells  and 
especially   of   tlic    normal   processes   of   oxidation.     It   is   therefore 
essential  for  the  preservation  of  life  that  the  acids  thus  formed  and 
accumulating  as  a  result  of  the  impaired  oxidative  processes  should 
be  neutralised,   carried  to  the  kidneys,   and  excreted  by  them  in 
combination  with  some  base.     When  these  acids  are  produced  in 
large  quantities  the  alkalies  of  the  food  and  of  the  tissues  do  not 
suffice  for  their  neutralisation.     Annuonia,  which  is  a  constant  inter- 
mediate stage  in  the  production  of  urea,  is  then  utilised  for  this  pur- 
pose and  the  acids  appear  in  the  urine  together  with  the  corresponding 
amount  of  ammonia.     The  anmionia  therefore   of   the   urme  gives 
valuable  information,  not  as  to  the  total  nitrogenous  exchanges  o£ 
the  body,  but  as  to  the  formation  of  acids  in  abnormal  quantities 
during  the  processes  of  metabolism. 

66 


866  PHYSIOLOGY 

There  is  one  other  method  in  which  urea  nuiy  be  formed  by  a  rapid 
aheration  of  the  proteins  taken  in  with  the  food.  Nearly  all  the 
ordinary  proteins  contain  ar<i;inine  as  an  integral  part  of  their 
molecule.  This  substance  can  be  regarded  as  formed  by  a  coupHng 
of  guanidine  with  amino- valerianic  acid  and  as  analogous  to  the  most 
prominent  extractive  of  muscle,  namely,  creatine,  which  is  methyl 
guanidine  acetic  acid.  On  heating  either  of  these  substances  with 
baryta  water  it  undergoes  hydrolysis  and  is  decomposed  with  the 
formation  of  urea  and,  in  the  case  of  arginine,  a-8-diamino-vaIerianic 
acid  ;  in  the  case  of  creatine,  methyl  amino-acetic  acid  or  sarcosine.  It 
has  been  shown  by  Dakin  and  Kossel  that  the  same  change  may  be 
effected  under  the  agency  of  a  ferment,  arginase,  which  is  contained 
in  extracts  of  the  intestinal  wall  or  of  the  hver.  We  have  every  reason 
to  believe  therefore  that  a  certain  small  proportion  of  the  urea  which 
appears  in  the  urine  after  the  ingestion  of  protein  is  due  to  this  hydro- 
lytic  splitting  of  the  arginine  contained  in  the  protein  molecule.  The 
other  moiety  of  the  arginine,  namely,  the  diamino-valerianic  acid, 
probably  undergoes  the  same  changes  as  the  other  amino-acids,  such 
proportion  of  it  as  is  not  required  for  the  building  up  of  the  tissues  of 
the  body  being  deaminised  and  giving  rise  to  urea  and  some  CHO  group 
in  the  manner  already  discussed. 

THE  ENDOGENOUS  OR  TISSUE  METABOLISM  OF  PROTEINS 
On  comparing  the  output  of  the  various  nitrogenous  excreta 
given  in  Folin's  tables  quoted  above  (p.  855),  we  see  that  on  a  low 
protein  diet,  when  the  exogenous  or  energy  metaboUsm  of  this  food- 
stuff is  reduced  to  a  minimum,  the  only  substance  which  does  not 
undergo  simultaneous  diminution  is  the  creatinine.  Whereas  on 
an  ordinary  diet  free  from  meat  it  only  accounts  for  about 
3  per  cent,  of  the  total  nitrogen  output,  on  the  low  diet  it  contains  as 
much  as  17  per  cent.  The  conclusion  at  once  suggests  itself  that 
creatinine,  more  than  all  the  other  constituents  of  the  urine,  must  be 
regarded  as  an  index  of  the  tissue  metabohsm  of  protein.  Let  us  see 
what  facts  can  be  adduced  in  favour  of  this  view. 
Creatinine  has  the  formula  : 

NH  =  C.N(CH3).CH2 

NH  —CO 

and  may  be  regarded  as  derived  by  a  process  of  dehydration  from 
creatine  (methyl  guanidine  acetic  acid). 

NH  =  C.N(CH3).CH,C00H 

I 
NH, 


PEOTEIN  METABOLISM  867 

It  may  be  formed  from  this  latter  substance  by  boiling  for  three  hours 
with  strong  hydrochloric  acid.  Creatine  has  long  been  known  as  the 
most  abundant  nitrogenous  extractive  in  the  body.  It  exists  in 
relatively  large  quantities  in  muscle,  and  in  meat  extracts,  such  as 
Liebig's,  it  occurs  to  the  extent  of  10  or  12  per  cent.  It  has  been 
calculated  that  the  body  of  a  man  at  any  time  contains  about  90  gim. 
of  this  substance.  On  boiling  creatine  with  baryta  water  it  undergoes 
hydrolysis  with  the  formation  of  urea  and  sarcosine  or  methyl  glycine. 

CH3  CH3 

^CN.CHaCOOH  +  H2O  =         ^CO  +  HN.CHoCOOH 

nh/  nh/ 

Creatine  Urea  Methyl  glycine 

Owing  to  the  ease  with  which  this  formation  of  urea  from  creatine 
may  be  brought  about  outside  the  body,  it  was  natural  that  this 
substance  should  be  regarded  as  an  important  precursor  of  the  urea 
in  the  urine.  The  view  was  held  till  recently,  however,  on  the  ground 
of  experiments  by  Voit,  that  creatine  administered  in  the  food  appeared 
in  its  entirety  as  creatinine  in  the  urine,  so  that  if  creatine  were 
liberated  from  the  muscles  in  their  normal  processes  of  metabolism 
it  would  pass  to  the  kidneys  and  be  excreted  as  creatinine  \\nthout 
undergoing  further  decomposition.  On  this  account  too  the  creatinine 
in  the  urine  was  regarded  as  derived  almost  exclusively  from  the 
creatine  taken  in  mth  the  food.  The  analyses  given  in  Fohn's  tables 
show  that  in  one  respect  at  any  rate  this  view  was  incorrect.  Creati- 
nine is  excreted  in  considerable  quantities  even  when  the  man  is  on 
a  creatine-free  diet,  or  even  when  his  food  is  almost  free  from  protein. 
It  has  been  foimd  moreover  by  Folin  that  creatine  administered  by 
the  mouth  may  be  entirely  oxidised  in  the  body.  This  is  especially 
the  case  if  the  animal  or  man  is  on  an  insufficient  protein  diet.  In 
most  cases  a  certain  proportion  escapes  decomposition  and  causes  an 
increase  in  the  quantity  of  creatinine.  Under  abnormal  circum- 
stances, c.(j.  during  illness,  when  the  physiological  activities  of  the 
body  are  lowered,  a  portion  of  the  creatine  may  be  found  in  the  urine 
in  an  unchanged  condition.  We  might  expect  to  find  therefore  that 
if  the  creatine  of  the  muscles  as  the  result  of  their  disintegi'ation  be 
discharged  into  the  blood,  a  portion  of  it  would  undergo  complete 
oxidation  with  the  formation  of  urea,  while  the  other  part  in  a  healthy 
individual  would  appear  in  the  urea  as  creatinine,  and  a  small  propor- 
tion under  conditions  of  diminished  vitality  might  pass  unchanged. 
If  creatinine  is  to  be  regarded  in  any  way  as  the  index  of  tissue  nu^ta- 
bolism  its  amount  ought  to  vary  with  the  extiMit  of  this  metabolism. 
Thus  it  should  be  increased  when  there  is  an  exaggeration  ot  the 


8G8  PHYSIOLOGY 

disintegrative  processes  in  the  tissues,  and  should  be  diminished  when 
the  nutritive  changes  in  these  tissues,  especially  in  the  muscles,  are 
reduced  to  a  minimum.  The  end-products  of  tissue  metabolism  there- 
fore should  be  increased  under  the  following  conditions  : 

(1)  Increased  motor  activity  involving  increased  wear  and  tear  of 
the  muscular  tissues. 

(2)  In  fevers,  especially  in  those  where  there  is  severe  toxaemia  and 
rapid  wasting  of  the  muscles  of  the  body. 

On  the  other  hand,  it  should  be  diminished  where  the  activity  of 
the  muscular  tissue  is  reduced  to  a  minimum,  as  under  the  influence 
of  sleep  or  soporifics,  or  where  the  bulk  of  the  muscular .  tissue  is 
reduced  as  well  as  its  activity,  as  in  cases  of  widespread  muscular 
atrophy  and  paralysis. 

The  excretion  of  creatinine  has  been  investigated  under  these 
various  conditions  by  Van  Hoogenhuyze  and  Verploegh,  and  their 
results  fully  bear  out  the  view  expressed  above  as  to  the  intimate 
relation  of  creatinine  with  the  tissue  metabolism  of  protein. 

During  protein  starvation  the  uric  acid  output,  though  diminished, 
does  not  show  a  change  which  is  at  all  proportional  to  that  shown  by 
the  urea.  This  substance  also  might  therefore  represent  an  end- 
product  of  tissue  metabohsm.  Since,  however,  uric  acid  is  an  out- 
come of  the  metabohsm  of  a  special  group  of  bodies,  the  nucleins  and 
purine  bases,  we  shall  have  to  devote  a  complete  section  to  its  con- 
sideration. 

Although  the  urea  is  diminished  in  protein  starvation,  it  still 
remains  the  most  abundant  nitrogenous  constituent  of  the  urine.  We 
are  therefore  not  justified  in  excluding  this  substance  from  the  pro- 
ducts of  tissue  metabohsm.  Creatine,  for  example,  may  undergo 
complete  oxidation  in  the  body,  so  that  during  protein  starvation  a 
certain  proportion  of  the  urea  may  be  derived  in  this  way.  We  shall 
see  later  that  uric  acid  may  also  undergo  further  oxidation  with  the 
formation  of  urea.  It  is  possible,  however,  that  even  during  complete 
protein  starvation  some  of  the  urea  which  is  turned  out  may  be  the 
expression  of  a  utilisation  of  protein  through  deamination  for  the 
energy  needs  of  the  body.  The  active  cells  are  bathed  everywhere 
with  a  tissue  fluid  in  which  proteins  form  a  preponderating  constituent, 
and  it  is  possible  that,  even  in  the  times  of  greatest  protein  need,  these 
cells  utihse  the  proteins  of  their  surrounding  medium,  though  in  a 
reduced  degree,  for  the  production  of  energy.  In  this  case  the  active 
cell  would  initiate  the  utilisation  by  throwing  off  that  part  of  the 
protein  molecule,  namely,  NH^,  which  is  useless  to  the  cell  as  a  source 
of  energy,  so  that  deamination  would  be  carried  out  in  the  worldng 
tissues,  and  not,  as  in  the  rapid  formation  of  urea  after  a  heavy  meal, 
in  the  tissues  of  the  intestine  and  liver. 


PROTEIN  METABOLISM  869 


SULPHUR 
Sulphur  occurs  in  the  urine  in  throo  ff)rras,  namely,  as  ordinary 
inorganic  sulphates,  as  ethereal  sulphates  (indoxy-  and  skatoxy-sul- 
phates),  and  in  an  unoxidised  condition  often  termed  neutral  sulphur. 
There  is  no  doubt  that  part  of  the  latter  consists  of  cystine,  part  of 
sulphocyanates,  and  in  some  animals  mercaptan  compounds.  The 
excretion  of  the  inorganic  sulphates  rises  fari  passu  with  that  of  the 
urea,  so  that  very  soon  after  the  thro^ving  off  of  the  NH,  group  there 
must  be  also  a  removal  and  oxidation  of  the  greater  part  of  the  sulphur 
contained  in  the  cystine  group  of  the  protein  molecule.  So  far  as 
regards  the  metabohsm  of  the  body  as  a  whole,  the  ethereal  sulphates 
may  be  classed  with  the  inorganic  sulphates.  They  are  excreted  in 
var}'ing  quantity  according  to  the  extent  of  the  decomposition  pro- 
cesses which  are  occurring  in  the  intestine.  Under  the  influence  of 
these  processes  the  tryptophane,  produced  in  the  pancreatic  digestion 
of  proteins,  is  converted  into  indol  and  skatol.  These  two  substances 
after  absorption  are  deprived  of  their  poisonous  quahties  by  oxidation 
and  conjugation  with  sulphuric  acid  to  form  the  indoxy-  and  skatoxy- 
sulphates  of  the  urine,  both  of  which  are  innocuous.  If  the  processes 
of  putrefaction  are  increased,  as  in  intestinal  obstruction,  the  relative 
amount  of  sulphate  appearing  in  the  conjugated  form  is  also  increased. 
On  administration  of  phenol  a  large  proportioii  of  the  sulphate  appears 
in  the  urine  conjugated  with  phenol  or  with  products  of  its  oxidation. 
If  the  normal  putrefactive  processes  w^hich  go  on  in  the  intestine  are 
abolished  by  the  administration  of  intestinal  antiseptics  such  as 
naphthalene  or  calomel,  the  ethereal  sulphates  practically  disappear 
from  the  urine.  We  cannot  therefore  regard  the  absence  or  diminution 
in  the  ethereal  sulphates  during  protein  starvation  as  throwing  any 
light  on  the  endogenous  protein  metabolism.  On  the  other  hand,  the 
fact  that  the  neutral  sulphur  undergoes  no  decrease  suggests  that  this 
part  of  the  sulphur  output  of  the  organism  may  be  connected  ^^^th 
tissue  metabohsm.  Further  observations  on  the  output  of  neutral 
sulphur  during  fever  or  wasting  diseases  are  necessary  before  a 
definite  conclusion  can  be  arrived  at  on  this  point. 

THE  FATE  OF  THE  AROMATIC  AND  OTHER  CYCLIC 
GROUPS  IN  THE  PROTEIN  MOLECULE 
A  typical  protein  such  as  can  be  utilised  as  a  complete  food-stuff 
contains,  in  addition  to  the  amino-acids  of  the  fatty  series,  a  number 
of  other  nitrogenous  derivatives  of  cyclic  com])()iinds,  including 
benzene,  indol,  pyrrol,  and  iminazol.  Substances  such  as  gelatin,  from 
which  some  of  these  groupings  are  absent,  camiot,  as  we  have  seen. 


870  PHYSIOLOGY 

entirely  replace  protein  in  the  food.  So  far  we  are  acquainted  with 
three  compounds  of  the  aromatic  series  among  the  prodncte  of  dis- 
integration of  the  protein  molecule.  Tliese  are  tyrosine,  phenylalanine, 
and  tryptophane.  Since  these  substances  arc  also  contained  in  the 
protein  constituents  of  the  tissues  we  may  assume  that,  after  they 
have  been  set  free  by  the  digestive  hydrolysis  of  proteins,  they  are 
absorbed  and  built  up  again  with  the  other  amino-acids  in  appropriate 
gTOupings.  Like  these  they  are  susceptible  of  complete  oxidation  in 
the  body,  so  that  they  can  contribute  to  the  supply  of  energy.  Any 
one  of  these  substances,  administered  mth  the  food  or  subcutaneously, 
is  entirely  destroyed,  with  the  production  of  urea,  carbon  dioxide, 
and  water.  In  this  respect  they  present  a  marked  contrast  to  almost 
all  other  compounds  of  the  aromatic  series.  In  these  we  find  that  the 
benzene  ring  is  extremely  stable,  so  that,  although  changes  may  occur 
in  its  side-chains,  the  benzene  ring  itself  appears  intact  in  tbe  urine, 
and  is  not  broken  up  in  the  body.  Thus  benzoic  acid,  benzylalcohol, 
and  phenyl  propionic  acid,  when  administered,  are  passed  in  the 
urine  as  hippuric  acid  (benzoyl  glycine).  Indol  and  skatol,  which 
are  closely  aUied  to  tryptophane,  undergo  oxidation  in  the  body 
without  further  modification  and  appear  in  the  urine  as  conjugated 
aromatic  sulphates. 

Some  light  is  thrown  on  the  conditions  of  breakdown  of  these 
aromatic  bodies  by  the  study  of  a  rare  disorder  in  metabohsm,  which 
may  occur  in  certain  famihes  and  is  known  as  alcaptonuria.  In  this 
condition,  which  is  congenital  and  lasts  throughout  life,  the  urine 
darkens  considerably  when  made  alkaline  and  exposed  to  the  air.  It 
has  the  power  of  reducing  Fehling's  solution,  so  that  the  presence  of 
sugar  might  be  suspected.  On  analysis  the  pecuharities  of  the  urine 
are  found  to  be  due  to  the  presence  in  it  of  a  substance  known  as 
homogentisic  acid.     This  is  dioxyphenyl  acetic  acid. 

\  /  ^H 
CH2COOH 

The  amount  of  this  substance  in  the  urine  bears  a  constant  ratio  to 
the  nitrogen  excreted.  It  does  not  disappear  during  starvation,  and 
is  much  increased  on  a  large  protein  diet.  It  must  therefore  be 
derived  from  the  disintegration  of  proteins  both  exogenous  and 
endogenous.  If  tyrosine  or  phenylalanine  be  administered  to  patients 
affected  with  this  disorder,  both  substances  are  quantitatively  con- 
verted into  homogentisic  acid.  The  ratio  of  this  acid  to  the  total 
nitrogen  indicates  that  the  whole  of  the  tyrosine  and  phenylalanine 
of  the  protein  molecule,  whether  set  free  in  the  alimentary  canal  or 


PROTEIN  METABOLISM  871 

in  the  tissue  metabolism,  is  converted  into  homogentisic  ar-ifl.      It 
is  not  possible  to  conceive  of  the  direct  conversion  of 


OH 


HO 


tyrosine 


into  homogentisic  acid 


OH 
CH2COOH 


CHo.CHNH^.COOH 
The  tyrosine  must  first  be  reduced  to  phenylalanine 


CH2.CTIXH2.COOH 

and  then  this  substance  must  undergo  oxidation  into  homo- 
gentisic  acid.  Since  phenyl  lactic  acid  and  phenyl  pyruvic  acid,  but 
not  phenyl  acetic  acid,  are  also  converted  in  alcaptonuric  patients  to 
homogentisic  acid,  it  has  been  suggested  that  these  two  substances 
form  stages  in  the  conversion  of  phenylalanine  into  homogentisic  acid. 
Thus 

HO    ^  ^ 


OH 

CHoCHOH.COOH      CH2CO.COOH  CH/'OOH 

Phf^nvlalaniuf-  Phenyl  pyruvic  Homogentisic 

It  is  further  thought  that  under  normal  circumstances  the  phenyl 
derivatives;  tyrosine  and  phenylalanine,  are  oxidised  to  homogentisic 
acid  as  in  the  alcaptonuric  patient.  In  the  normal  indi\-idual.  how- 
ever, the  introduction  of  two  hydroxyl  groups  into  the  benzene  ring 
leads  to  some  process,  perhaps  of  a  ferment  character,  which  breaks  up 
the  ring.  This  ferment  is  absent  in  the  alcaptonuric,  so  that  the  trans- 
formation of  the  phenyl  derivatives  stops  short  at  the  stage  of  homo- 
gentisic acid  (Garrod).  The  eminently  specific  character  of  this  process 
is  shown  by  the  fact  that  although  these  various  substances  undergo 
complete  oxidation  in  the  body,  a  slight  modification  in  the  chain  of 
the  processes  renders  the  change  impossible.  Thus  if  the  side  group 
in  phenyl  lactic  or  phenyl  pyruvic  acid  be  converted  to  acetic  acid 
before  the  introduction  of  the  two  OH  groups  into  the  phenyl  ring, 
the  phenyl  acetic  acid  thus  produced  is  incapable  of  undergoing 
further  oxidation.  Tyrosine  in  the  intestine  undergoes  deamination 
to  form  oxyphenyl  propionic  acid  and  oxyphenyl  acetic  acid.  These 
cannot  be  further  oxidised,  but  appear  in  the  urine  as  such  or.  after 
conversion  into  kresol  or  phenol,  as  sulphuric  acid  esters. 


872  PHYSIOLOGY 

Somewhat  similar  conditions  apply  to  the  oxidation  of  tryptophane. 
This  body  is  an  indol  derivative  and  consists  of  a  benzene  ring 
and  a  pyrrol  ring  having  two  of  their  carbon  atoms  in  common.  Its 
formula  is 

HC  C — C.CHaCHNHa.C'OOH 


>CHs 


HC  C  CH 

^CH^   ^H 

i.e.  it  is  indol  amino-propionic  acid.  It  undergoes,  like  tyrosine, 
complete  oxidation  in  the  body.  On  the  other  hand,  a  very  slight 
alteration  in  the  molecule  renders  it  incapable  of  this  change.  Thus 
the  trytophane  set  free  by  the  tryptic  digestion  of  proteins  under  the 
influence  of  the  putrefactive  bacteria  of  the  intestine  may  undergo 
deamination  and  reduction  with  the  production  of  indol  propionic 
acid,  and  this  by  oxidation  may  be  converted  to  indol  acetic  acid. 
The  latter  substance  by  decarboxylation  may  be  converted  into  skatol, 
or  by  oxidation  nearer  the  chain  and  further  loss  of  carbon  dioxide 
into  indol.  Of  these  products  of  bacterial  change,  indol  acetic  acid 
may  be  found  in  the  urine,  and  indol  and  skatol  are  oxidised  to  the 
corresponding  phenols  and  pass  into  the  urine  conjugated  either  with 
sulphuric  acid  or  with  glycuronic  acid.  Apart,  however,  from  these 
putrefactive  changes  due  to  bacteria,  no  indol  derivatives  pass  into 
the  urine.  The  amount  of  the  indol  and  skatol  esters  serves  therefore 
merely  as  an  index  of  bacterial  decomposition  in  the  alimentary  canal, 
and  gives  us  no  clue  to  the  total  tryptophane  metabolism  of  the  body. 
If  putrefaction  be  prevented  by  the  administration  of  calomel  or 
other  intestinal  antiseptic  these  esters  may  entirely  disappear  from 
the  urine.  On  the  other  hand,  the  partial  obstruction  to  the  onw^ard 
passage  of  food,  caused  by  dividing  the  small  intestine  in  two  places 
a  few  inches  apart  and  replacing  the  intervening  length  of  intestine 
the  wrong  way  round,  causes  the  indican  excretion  to  be  increased 
twenty  or  thirty  fold.  Subcutaneous  injection  of  tryptophane  in 
rabbits  does  not  increase  the  indoxyl  and  skatoxyl  sulphates  (urinary 
indican)  in  the  urine,  whereas  a  considerable  increase  is  brought  about 
by  subcutaneous  injection  of  indol. 

The  pyrrol  ring  which  occurs  in  proteins  as  proline  and  oxyproline 
(?".c.  pyrrolidine  carboxyUc  acid  and  oxypyrrolidine  carboxylic  acid) 
appears  to  undergo  complete  disintegration  in  the  body.  The  steps 
in  this  conversion  are  unknown,  though  it  is  possible  that  the  ring 
may  be  unhnked  so  as  to  produce  from  the  pyrrol  ring  amino-valerianic 
acid,  which  would  then  undergo  the  process  of  deamination  with  which 
we  are  already  familiar.     This  ring  is  of  interest  since  it  appears  to 


PROTEIN"  METABOLISM  873 

take  an  important  part  in  the  building  up  of  the  molecule  of  hsBmatin, 
the  essential  prosthetic  group  of  the  hsemogloliiu  molecule. 

Another  ring  grouping,  iminazol,  occurs  in  histidine,  which  is 
iminazol  a-amino-propionic  acid.  This  too  undergoes  complete  oxida- 
tion in  the  body.  It  is  important  to  bear  in  mind  that  this  ring  may 
be  produced  synthetically  by  very  simple  means,  i.e.  by  the  action  of 
zinc  oxide  and  ammonia  on  glucose,  which  results  in  a  rich  yield  of 
methyl  iminazol  [v.  p.  130).  The  same  grouping  is  found  in  creatinine, 
as  is  seen  by  comparing  the  formulae  : 


^C=NH 
OC— NH 

HC— NH 

II            >H 
HC— N    ^ 

Creatinine 

Iminazol 

and  it  is  possible  that  this  may  furnish  a  clue  to  the  mode  of  formation 
of  creatinine  in  muscle.  Creatine  has  generally  been  regarded  as 
the  primary  product  of  muscular  metaljolism,  but  it  is  possible  that 
the  ring- grouping  is  the  original  one  and  that  creatine  is  produced 
by  hydrolysis  occurring  in  this  ring. 

The  iminazol  group  is  at  present  chiefly  interesting  in  that  it 
contributes  to  the  formation  of  the  complex  ring  compounds  known 
as  the  purines.  Since  the  purine  metabolism  is  closely  connected 
with  the  question  of  the  origin  of  uric  acid  we  may  consider  these 
questions  together. 


SECTION  II 

NUCLEIN  OR  PURINE  METABOLISM 

In  an  undifierentiated  cell  the  proteins,  as  such,  form  but  a  small 
part,  the  mass  of  the  cell  being  composed  of  conjugated  proteins. 
The  nucleo-proteins  are  especially  abundant  constituents  of  nuclei, 
and  therefore  occur  to  a  greater  or  less  extent  in  all  the  ordinary 
animal  foods,  eggs  and  milk  excepted.  Just  as  the  metabolism  of 
proteins  is  the  metabohsm  of  the  amino-acids,  so  the  metabolism 
of  the  nucleo-proteins  and  nucleins  is  essentially  comprised  in  the 
history  of  its  main  constituents,  i.e.  the  purines. 

The  nucleo-proteins  themselves  ^re  bodies  of  very  varying  composi- 
tion. If  any  cellular  tissue  such  as  thymus  or  liver  be  extracted  with 
water  or  salt  solution,  a  fluid  is  obtained  from  which  a  precipitate 
can  be  thrown  down  by  the  addition  of  acid.  This  precipitate  as  a 
rule  is  soluble  in  excess  of  acid  or  in  alkahes.  If  subjected  to  gastric 
digestion  it  undergoes  solution,  leaving  behind  a  residue  of  nuclein 
which  is  rich  in  phosphorus.  The  amount  of  this  residue  varies 
with  the  strength  of  the  artificial  gastric  juice  employed,  so 
that  the  method  cannot  be  looked  upon  as  in  any  way  quantitative, 
and  the  question  arises  whether  the  original  nucleo-protein  is  to  be 
regarded  as  an  association  or  a  combination  of  nuclein  with  ordinary 
protein.  The  most  convenient  source  for  the  preparation  of  nucleins 
is  the  heads  of  fish  spermatozoa.  All  nucleins  are  associations  or 
compounds  of  nucleic  acids  with  proteins  belonging  to  the  class  of 
protamines  or  histones.  The  nucleins  of  fish  spermatozoa  contain 
protamine  as  one  of  their  constituents.  On  separating  off  the 
protamine,  nucleic  acids  can  be  isolated.  These  acids  have  been 
named  either  according  to  their  source  or  according  to  the  purine  base 
which  is  their  most  prominent  constituent.  Only  from  inosinic  acid, 
the  nuclein  acid  of  muscle,  has  it  been  found  possible  to  prepare 
crystalline  derivatives,  so  that  in  all  other  cases  it  is  difficult  to 
decide  whether  we  are  dealing  with  chemical  individuals  or  with 
mixtures. 

On  hydrolysing  any  of  the  nucleic  acids  by  heating  with  strong 
mineral  acid,  they  are  broken  down  into  a  series  of  bodies  belonging 
to  the  following  four  groups  :  (1)  phosphoric  acid,  (2)  purine  bases, 
(3)  pyrimidine  bases,  (4)  a  carbohydrate.  The  purine  bases  obtained 
from  the  hydrolysis  of  nucleic  acid  are  guanine,  adenine,  hypoxanthine, 
and  possibly  xanthine.     The  last  two  bodies  are  probably  secondary 

874 


NUCLEIN  OR  PURINE  METABOLISM  875 

products  of  the  deamination  and  oxidation  of  guanine  and  adenine. 
Fischer  has  shown  that  all  these  bodies  are  derivatives  of  a  base 
purine.  They  contain  a  central  chain  of  three  carbon  atoms  to 
which  is  attached  on  each  side  a  urea  group,  so  that  they  may  be 
regarded  as  diureides.     Purine  itself  has  the  formula 

N=CH 

HC      C— NH 

II       II        >H 

N— C— n/^ 

Purine 
The  relation  of  the  purine  bases  obtained  from  disintegration  of  nucleic 
acid  to  purine  itself  has  been  given  on  p.  114.  From  these  formulae 
we  see  that  adenine  and  hypoxanthine  are  related  to  one  another, 
adenine  being  6-aminopurine,  while  hypoxanthine  is  6-oxypui'ine. 
In  the  same  way  guanine  and  xanthine  are  related,  guanine  being 
2-amino-G-oxypurine,  while  xanthine  is  2-6-oxypurine.  The  investiga- 
tion of  the  relationships  of  these  bases  was  of  interest  to  physiologists 
since  it  brought  to  light  the  close  relation  which  they  have  to  uric 
acid,  a  substance  which  has  been  kno^vn  as  a  constituent  of  urine 
and  urinary  calculi  for  a  long  time,  having  been  discovered  in  1776  by 
Scheele.     Uric  acid  is  a  2-G-8-trioxypurine  and  has  the  formula 

HN— CO 

CO    C— NHx 

I      11  >o 

HN— C— NH^ 

Uric  acid  =  2-6-8-trioxypurine 

In  uric  acid  the  two  urea  groups  are  attached  to  a  central  3-carbon 
chain,  and  it  is  interesting  tojnote  that  one  of  the  first  syntheses  of 
uric  acid,  namely,  that  by  [Horbaczewski,  was  accomplished  by 
melting  together  trichlorlactamide  and  urea  in  a  sealed  tube. 

Belonging  to  the  same  group  of  purines  are  the  two  bases  which 
form  the  essential  constituents  of  tea,  coffee  ^  and  cocoa.  In  tea  and 
cofiee  is  found  caffeine,  which  is  l-3-7-trimethyl-2-G-dioxypurine,  and 
in  cocoa  occurs  the  closely  allied  theobromine,  which  is  3-7-dimethyl- 
2-6-dioxypurine.  Caffeine  is  thus  methyltheobromine. 
CH3N— CO  HN— CO 


CO  C— N\  CO  C—N( 

I      II        >CH  I       II        >CH 

CH3N— C— N^  CH3N— C— N^ 

Caffeine  =  l-;i-7-tnmc(liyI-  Tlu>()l)romine=3-7-(limothyl- 

2-6-dioxypurino  2-B-dioxypurinc 


876 


PHYSIOLOGY 


The  pyrimidine  bases  which  are  also  obtained  from  the  hydrolysis 
of  nucleic  acid  are  derived  from  a  pyrimidine  nucleus  which  is,  so  to 

speak,  half  a  purine  nucleus,  consisting  of  a  C(         chain  joined  to  a 

■N 
3-carbon  chain.     Three  pyrimidine  bases  have  been  isolated  from  the 
decomposition   products  of  nuclein,  namely,  thymine,  cytosine,  and 
uracil. 


NH  — CO 


NH  — CO 


N    =    O.NH, 


CO       CH 


CO 


C.CH, 


CO 


CH 


NH  — CH 

Uracil  2-6-dioxy- 
pyrimidine 


NH  — CH 

Thymine  5-methyl- 
m-acil 


NH  — CH 

Cytosine  G-amino- 
2-oxypyrimidino 


Cytosine  is  easily  converted  by  oxidation  into  uracil. 
After  separation  of  the  purine  and  pyrimidine  bases  and  phosphoric 
acid  a  substance  is  left  over  which  gives  the  reactions  of  a  carbo- 
hydrate. This  carbohydrate  residue  differs  in  different  nucleic  acids. 
The  only  one  which  has  been  so  far  isolated  is  a  pentose,  namely, 
?- xylose.  It  is  stated  that  the  nucleic  acids  of  yeast  and  of  the  thymus 
gland  yield  a  hexose.  In  most  cases  it  is  impossible  to  say  how  far 
these  different  bodies  are  combined  to  make  up  nucleic  acid.  From 
muscle  an  acid  of  the  same  class,  inosinic  acid,  can  be  extracted  which 
yields  crystalline  barium  and  calcium  salts.  This  has  been  found  to 
consist  of  one  molecule  each  of  hypoxanthine,  xylose,  and  phosphoric 
acid.  According  to  Neuberg,  it  has  probably  the  following  constitu- 
tional formula  : 


(1)  HN— (6)  CO 

(2)  HC     (5)  C— (7)  N- 


II  II  J 

(3)     N— (4)  C— (9)  N^ 


(8)CH 


0 


.OH 


0 


CH— 


CHpOH 


N^UCLEIN  OR  PURINE  METABOLISM  877 

The  nucleic  acid  obtained  from  the  pancreas  apparently  contains 
one  molecule  each  of  Z-xylose,  phosphoric  acid,  and  guanine,  and  is 
therefore  spoken  of  as  guanylic  acid.  In  the  same  way  an  adenjlic 
acid  has  been  described  which  contains  only  adenine,  phosphoric  acid, 
and  a  pentose. 

FORMATION  OF  NUCLEINS  IN  THE  BODY 
In  the  case  of  the  proteins  we  saw  reason  to  believe  that  in  the 
higher  animals,  at  any  rate,  there  was  no  power  of  converting  one 
amino-acid  into  another  (with  the  exception  of  the  lowest  member  of 
the  series,  namely,  glycine),  and  that  on  this  account  the  food  had  to 
contain  representatives  of  every  amino-acid  (or  perhaps  of  the  corre- 
sponding oxy-fatty  acid)  necessary  to  the  building  up  of  the  tissue 
proteins.  The  nucleins,  on  the  other  hand,  can  certainly  be  synthetised 
by  the  animal.  This  is  shown  by  the  fact  that  the  hen's  egg  before 
incubation  contains  practically  no  nuclein  or  purine  bases.  During 
incubation  tissues  are  formed,  and  there  is  a  rapid  increase  in  the  number 
of  nuclei,  so  that  the  chick  just  before  it  is  hatched  contains  a  consider- 
able amount  of  nuclein  from  which  purine  bases  can  be  extracted. 
This  nuclein  must  have  been  formed  by  a  synthesis  from  the  phospho- 
proteins  and  phosphatides  (phosphorised  fats)  which  form  so  prominent 
a  constituent  of  the  egg- yolk,  and  in  the  same  way  the  purines  must 
have  been  formed  by  a  process  of  synthesis.  This  synthesis  may 
occur  by  a  conjugation  of  two  urea  molecules  with  the  3-carbon  chain 
which  is  so  prominent  a  feature  in  the  proximate  principles  of  the 
body  {e.g.  in  lactic  acid,  alanine,  and  all  the  compound  amino-acids 
of  which  alanine  is  a  constituent).  Methyliminazol,  representing  one- 
half  of  the  purine  ring,  can  be  formed  simply  by  allowing  ammonia 
and  glucose  to  stand  in  contact  with  zinc  hydroxide.  The  power  of 
synthesis  of  purines  possessed  by  the  body  must  comphcate  the  question 
of  their  fate  after  ingestion,  since  it  is  evident  that  they  can  either  be 
destroyed  and  excreted  in  some  other  form  or  that  the  products  of  their 
destruction  may  be  built  up  into  fresh  purine  or  nuclein  molecules.  In 
the  same  w^ay,  in  the  growing  child  there  is  a  rapid  increase  in  the 
nuclein  of  the  body,  although  the  only  food  ingested  is  milk,  which 
contains  but  an  insignificant  amount  of  nuclein. 

FATE  OF  NUCLEINS  IN  THE  BODY 
Nucleins  and  nucleic  acids  are  dissolved  by  the  pancreatic  juice, 
but  no  digestion  of  the  nucleic  acid  occurs  in  the  ahmentary  tract 
other  than  by  the  action  of  micro-organisms.  We  must  assume  there- 
fore that  the  nucleic  acid  is  taken  up  by  the  cells  of  the  intestinal  wall 
unchanged.  Most  cells  of  the  body  contain  nucleases,  i.e.  ferments 
capable  of  hydiolysing  nucleic  acids  and  of  setting  fi-ee  their  purine 


878  PHYSIOLOGY 

constituents.  It  has  been  shown  that  digestion  of  the  primary 
purine  bases  of  most  nucleic  acids,  namely,  guanine  and  adenine,  with 
extracts  of  tissues  such  as  the  liver,  converts  these  bodies  into  hypo- 
xanthine  and  xanthine,  the  change  involved  being  one  of  deamination. 
as  is  evident  from  comparing  the  formula)  of  these  bodies. 

N=C— NH2  NH— CO 

HC     C— NH  NH2.C       C— NH 

11      II        ^CH  II        II         ^CH 

N— C— N^  N  — C— N/ 

Adenine  Guanine 

HN  —  CO  HN  —  CO 

II  II 

HC         C  — NH  CO     C  — NH 

Hypoxanthine  Xanthine 

Under  the  action  of  other  oxidising  ferments  also  contained  in 
tissues  xanthine  may  be  converted  into  uric  acid.  If  spleen  pulp  be 
digested  with  blood  for  some  time  it  is  possible  to  extract  a  consider- 
able amount  of  xanthine  from  the  mixtme.  If,  however,  oxygen  be 
bubbled  through  the  mixture  the  xanthine  disappears,  its  place  being 
taken  by  uric  acid.  It  is  evident  that  these  changes,  resulting 
ultimately  in  the  formation  of  uric  acid,  might  affect  either  the 
nucleins  derived  from  the  food  or  any  nucleins  set  free  by  disintegra- 
tion of  the  tissues  of  the  body  itself.  Uric  acid  being  a  constituent  of 
urine,  we  might  therefore  assign  to  it  a  twofold  origin,  namely, 
(a)  exogenous  from  the  nucleins  of  the  food,  (6)  endogenous  from  the 
nucleins  of  the  tissues.  This  would  not,  however,  exhaust  all  the 
possibilities.  We  have  seen  already  that  in  the  bird  the  gieater  part 
of  the  uric  acid,  which  represents  the  chief  nitrogenous  excreta,  is 
formed  not  from  purines  at  all,  but  by  a  process  of  synthesis  from 
lactic  acid  and  ammonia.  This  synthesis  occurs  in  the  liver,  so  that 
after  extirpation  of  this  organ  the  place  of  the  uric  acid  in  the  urine 
is  taken  by  lactic  acid  and  ammonia.  Though  we  have  no  evidence 
of  a  similar  change  taking  place  in  the  mammal,  we  cannot  exclude 
the  possibility  of  some  formation  of  uric  acid  by  a  process  of 
synthesis. 

Even  after  uric  acid  is  formed  in  any  of  the  ways  mentioned  abovo^ 
it  does  not  necessarily  follow  that  it  will  be  excreted  as  such.  Uric 
acid  may  be  further  broken  down  in  the  bod\',  as  it  is  outside  the 
body,  under  the  action  of  oxidising  agents.     Thus  if  nitric  acid  be 


NUCLEIN  OR  PURINE  METABOLISM  879 

allowed  to  act  upon  uric  acid  it  splits  ofi  the  right-hand  group,  forming 
urea  and  a  body  known  as  alloxan. 

NH-CO  iNHH-CO 

II  II 

CO       C  — NHv  CO       CO     NH, 

I  II  )cO  +  H,0  +  0=  I  I     +         /CO 

NH  —  C  —  NH^  NH  —  CO     NH/ 

Further  oxidation  converts  the  alloxan  into  parabanic  acid, 

NH  —  CO 


CO 


and  CO2J 


NH  — CO 

and  parabanic  acid  by  hydrolysis  is  finally  converted  into  oxalic  acid, 

CO  — OH 
I  and  urea. 

CO  —  OH 

Potassium  permanganate,   on  the  other  hand,  attacks  the  central 
3-carbon  chain  at  once,  forming  allantoin. 

NH      CO      NH2 


CO 


CO        and  CO.,. 


NH  —  CH  —  NH 

From  the  allantoin  by  processes  of  oxidation  and  hydration  both  urea 
groups  may  be  split  off  as  before. 

If  uric  acid  be  given  to  a  man  there  is  no  proportional  increase  of 
the  uric  acid  in  the  urine.  It  has  been  shown  by  Schittenhelm  that 
many  tissues  contain  uricolytic  ferments  which  have  the  property  of 
breaking  down  and  oxidising  uric  acid.  This  oxidation  may  be 
complete  or  incomplete.  In  the  former  case  the  uric  acid  administered 
will  appear  in  the  urine  simply  as  urea.  In  the  latter  it  may  appear 
as  one  of  the  products  already  described,  e.g.  oxalic  acid  or  allantoin. 
In  the  dog  uric  acid  is  practically  absent  from  the  urine,  allantoin 
taking  its  place,  and  uric  acid  administered  to  this  animal  gives  rise 
to  a  corresponding  but  not  equal  increase  in  the  allantoin  of  the  urine. 

EXCRETION  OF  URIC  ACID 
The  complexity  of  these  various  processes  in  man  renilors  it  a 
difficult  task  to  form  a  clear  idea  of  the  origin  of  the  urinary  uric 
acid  and  of  the  conditions  which  determine  the  variations  in  the  amount 


880 


PHYSIOLOGY 


excreted  at  different  times.  Under  ordinary  circumstances  a  man 
excretes  about  half  a  gramme  of  uric  acid  per  day.  In  addition  the 
urine  contains  a  certain  small  amount  of  purine  bases,,  the  ratio  of 
these  bases  to  the  uric  acid  being  generally  about  1  :  6.  From  10,000 
litres  of  himian  urine  Kriiger  and  Salomon  succeeded  in  isolating  the 
follo^ving  purine  bases  : 

Xanthine       .         .         .      10-1  grm. 
Hypoxanthine        .         .        8-5     ,, 
Adenine         .         .         .        3-5     ,, 

The  same  urine  would  probably  have  contained  about  500  grni.  of 
uric  acid.  As  we  should  expect,  the  amoimt  of  uric  acid  in  the  urine 
varies  with  the  diet.  The  following  Tables  from  Bunge  give  the  com- 
position of  the  urine  secreted  (1)  on  a  mixed  diet,  (2)  on  a  diet  mainly 
composed  of  meat,  (3)  on  a  diet  mainly  composed  of  bread : 


Twenty-four  hours 

Mixed 

Meat 

Bread 

Quantity  c.c.        .          .         . 
Urea        ....   grm. 

1500 

1672 

1920 

33 

67 

20 

Uric  acid 

•55 

13 

•25 

Ammonia 

•9 

2^1 

•9 

Creatinin 

•77 

•9 

•4 

Hippuric  acid  . 

•4 

— 

— 

Sulphates 

2 

4^6 

12 

Sodium  chluridf 

10^5 

7^5 

8^2 

Phosphates 

316 

3-4 

1-6 

Potassium 

, 

2o 

3-3 

1-3 

Calcium,  magu 

esium 

,  ire 

)U,  c 

alouring-mattc 

•r,  gases,  ferm 

ents. 

An  attempt  has  been  made  to  arrive  at  the  amount  of  uric  acid 
produced  endogenously,  i.e.  from  the  breakdown  of  the  tissues,  from 
a  study  of  the  amount  of  uric  acid  in  the  urine  under  varying  conditions 
of  food.  During  starvation,  when  the  man  is  living  on  his  owti  tissues, 
one  might  expect  the  uric  acid  to  be  increased  in  consequence  of 
disintegration  of  the  tissues.  It  has  been  suggested  that  the  amount 
of  the  endogenous  uric  acid  in  the  urine  would  be  obtained  by  an 
analysis  of  the  urine  from  patients  taking  a  diet  free  from  purine 
bases,  but  containing  sufficient  nitrogen  to  maintain  nitrogenous 
equilibrium.  It  is  impossible,  however,  to  arrive  at  any  constant 
figure  for  the  endogenous  uric  acid.  Even  in  the  entire  absence  of 
purine  derivatives  from  the  body  the  amount  of  uric  acid  increases 
with  the  total  nitrogenous  metabolism.  This  fact  is  well  shown  in  the 
Tables  by  FoUn  (ah'eady  quoted)  of  the  composition  of  the  urine  on  a 


NUCLEIN  OR  PURINE  METABOLISM 


881 


low  and  a  high  protein  diet  respectively.  Although  in  each  case 
care  was  taken  to  exclude  purine-containing  bodies  from  the  food, 
the  output  of  uric  acid  on  the  high  nitrogenous  diet  was  double  as 
much  as  on  the  low  diet.  All  we  can  say  is  that  uric  acid  is  constantly 
beinc  derived  from  the  tissue  disintegration,  but  that  it  varies  under 
different  conditions  of  nutrition  as  well  as  under  different  conditions  of 
activity  of  the  body. 

There  are  two  main  conditions  which  give  rise  to  a  marked  increase 
in  the  output  of  endogenous  uric  acid.  These  are  (1)  severe  muscular 
activity,  (2)  febrile  states  accompanied  by  increased  nitrogenous  meta- 
boUsm.  Since  both  these  conditions  are  associated  with  an  increased 
breakdown   of   muscle   substance  we    may  regard   the  uric  acid  as 


uu 

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Fig.  353.  Curves  showing  the  hourly  excretion  of  uric  acid  and  urea  after  a  single 
meal.  (Hopkins.)  The  continuous  line  ==  uric  acid  output;  the  dotted 
line  =  urea  output. 

derived  especially  from  the  hypoxanthinc  or  its  precursors,  such  as 
inosinic  acid,  contained  in  the  muscle. 

The  foods  which  are  especially  effective  in  causing  increase  in  the 
exogenous  uric  acid  are  those  rich  in  nuclein,  such  as  sweetbreads 
or  liver,  and  those  rich  in  hypoxanthine  or  its  precursors,  such  as  meat 
or  meat  extract.  When  these  foods  are  taken,  or  when  nucleic  acid 
itself  is  administered,  a  condition  of  leucocytosis  is  generally  produced, 
the  number  of  leucocytes  in  the  blood  being  increased  as  much  as 
three  times.  It  has  been  suggested  that  the  uric  acid  is  actually 
formed  by  a  disintegration  of  the  newly  formed  leucoc}i:es  and  not  by 
a  direct  conversion  of  the  purines  of  the  food.  It  is  quite  possible,  as 
suggested  by  Scliittenhelm,  that  the  leucocytes  play  a  i)art  in  the 
transference  of  the  nucleins  from  the  intestine  to  the  circulation.  But 
the  absence  of  any  absolute  proportionality  between  the  degree  of 
leucocytosis  and   the    amount  of  uric   acid   excreted    points  to  the 


882  PHYSIOLOGY 

probability  of  a  direct  conversion  of  tbe  purines  of   the  food  into 
uric  acid. 

In  man  only  very  small  traces  of  allantoin  are  to  be  found  in  the 
urine,  so  that  we  must  assume  that  any  uric  acid  which  is  destroyed 
by  the  process  of  uricolysis  is  broken  down  into  urea,  and  probably 
appears  as  such  in  the  urine. 

URIC  ACID  IN  GOUT 
Gout  is  a  condition  in  which  deposits  of  urate  of  soda  occur  in  the 
cartilages  of  the  joints,  the  great  toe  joint  being  the  seat  of  predilection 
for  this  disorder.  The  deposit  is  generally  associated  with  an  acute 
inflammation  of  the  joint.  In  normal  indi\'iduals  the  amount  of  uric 
acid  in  the  blood  is  too  small  to  be  detected.  Uric  acid  is  readily 
excreted  by  the  healthy  kidneys.  If  the  output  of  uric  acid  be  largely 
increased  by  the  administration  in  large  cjuantities  of  food-stuffs  rich 
in  purines,  it  becomes  possible  to  demonstrate  the  actual  presence 
of  uric  acid  in  the  blood.  In  gout  there  is  constantly  an  increased 
amount  of  uric  acid  in  the  blood,  probably  in  the  form  of  sodium 
urate,  even  when  the  patient  is  on  a  purine-free  diet,  so  that  gout  may 
be  regarded,  from  one  point  of  view  at  any  rate,  as  a  uricaemia  of 
endogenous  origin.  On  the  other  hand,  the  output  of  uric  acid  in  the 
urine  is  not  increased,  and  may  in  fact  be  somewhat  smaller  than 
normal.  It  might  be  thought  that  the  presence  of  uric  acid  in  the 
blood  must  therefore  be  due  to  diminished  power  of  excretion  of  this 
substance  by  the  kidneys.  This  view  is  negatived  by  the  fact  that  if 
uric  acid  be  injected  subcutaneously  into  gouty  subjects  it  is  excreted 
in  the  urine  exactly  in  the  same  way  and  as  rapidly  as  in  normal 
persons.  It  has  therefore  been  suggested  that  gout  consists  essentially 
in  a  disturbance  in  the  various  fermentative  mechanisms  which  are 
responsible  for  the  changes  undergone  by  the  purines  as  well  as  by  the 
uric  acid  itself,  so  that  there  is  an  increased  amount  not  only  of  uric 
acid  itself  bub  of  the  various  intermediate  products  in  its  formation 
from  the  purine  bases  of  the  food  and  of  the  tissues.  The  deposit  of 
the  uric  acid  in  the  joint  cartilages  characteristic  of  acute  gout  seems 
to  be  simply  a  crystalUsation  of  urate  of  soda  from  a  supersaturated 
solution  of  this  substance  in  the  blood.  The  whole  question  of  the 
pathology  of  gout  and  of  the  disordered  metaboUsm  which  may 
precede  or  intervene  between  actual  acute  attacks  of  the  disease  is 
in  need  of  further  investigation.  Especially  is  it  important  to  deter- 
mine the  influence  on  this  condition  not  only  of  the  nucleins  and 
proteins  of  the  food,  but  of  the  other  constituents,  such  as  carbo- 
hydrates and  fats.  Speaking  broadly,  gout  is  a  disease  of  the 
well-to-do,  of  the  person  who,  while  pursuing  a  sedentary  or  no  occupa- 
tion, is  not  Umited  in  his  food-supply.     It  is  almost  unknown  in  the 


NUCLEIN  OR  PURINE  METABOLISM  883 

labouring  class,  where  hard  manual  work  is  combined  with  a  bare 
sufficiency  of  food.  It  seems  therefore  that  it  is  not  so  much  the 
supply  of  purines  in  the  diet  which  must  be  controlled  as  the  general 
conditions  of  nutrition  which  determine  the  fermentative  changes  in 
the  purines,  either  of  the  food  or  tissues,  under  normal  conditions  of 
metabolism. 


SECTION  III 

THE  HISTORY  OF  FAT  IN  THE  BODY 

Fat  is  found  in  the  body  in  various  situations.  In  a  fat  animal 
the  largest  amount  occurs  in  the  panniculus  adiposus  in  the  sub- 
cutaneous tissues.  Large  quantities  are  also  found  surrounding  the 
abdominal  organs  and  between  the  layers  of  the  mesentery  and  great 
omentum.  In  this  adipose  tissue  the  fat  is  enclosed  within  and 
distends  connective-tissue  cells,  the  protoplasm  of  which  is  reduced  to 
a  thin  pellicle  round  the  fat  globule.  Fat  is  also  found  in  the  form 
of  granules  in  more  highly  specialised  cells,  such  as  the  secreting  cells 
of  the  liver  or  the  muscle-cells.  The  condition  of  these  cells  is  often 
spoken  of  as  fatty  infiltration,  or  fatty  degeneration,  according  to 
the  circumstances  which  are  responsible  for  bringing  about  the 
deposition  of  fat.  We  shall  have  to  discuss  later  on  how  far  we  are 
justified  in  assuming  any  real  distinction  between  these  two  processes. 
From  the  physiological  standpoint  the  most  important  intracellular 
depot  of  fat  is  in  the  fiver.  If  this  organ  be  deprived  of  glycogen  and 
fat  by  starvation,  a  fatty  meal  gives  rise  to  a  great  deposition  of  fat 
in  its  cells.  There  is  apparently  an  antagonism  between  the  processes 
which  lead  on  the  one  hand  to  the  deposition  of  glycogen  and  on  the 
other  to  the  deposition  of  fat.  Thus  an  excessive  carbohydrate  diet, 
which  induces  great  deposition  of  fat  in  the  subcutaneous  tissues,  only 
causes  the  formation  of  glycogen  in  the  liver.  The  glycogen  must  be 
got  rid  of  before  it  is  possible  to  cause  the  deposition  of  fat.  On  this 
account,  the  normal  content  in  fat  of  the  livers  of  different  animals 
varies  with  their  ordinary  diet.  Fishes,  e.g.  the  cod,  which  take  but 
little  carbohydrate  in  their  food  have  generally  a  very  large  quantity 
of  fat  in  their  livers.  Herbivorous  animals,  as  a  rule,  have  practically 
no  fat  in  the  liver. 

Fat  also  occurs  in  certain  secretions,  e.g.  the  milk  and  the  sebum, 
its  function  in  the  latter  case  being  mainly  protective. 

Besides  the  visible  deposit  of  fat  found  in  adipose  tissue  and  in 
other  situations  a  large  amount  of  fat  is  always  present  built  up  into 
the  protoplasm  of  the  cells  in  such  a  condition  that  its  presence  cannot 
be  detected  by  histological  means.  The  presence  or  absence  of  visible 
fatty  globules  affords  very  fittle  clue  to  the  total  quantity  of  fat  in  the 
cells.  Thus  in  one  case  the  heart  muscle,which  had  undergone  extreme 

884 


THE  HISTORY  OF  FAT  IN  THE  BODY  885 

fatty  degeneration  and  was  loaded  with  fat  globules,  contained  19  per 
cent,  of  its  dried  weight  of  fat.  A  heart  muscle  taken  from  a  normal 
animal  at  the  same  time,  presenting  no  visible  fat  globules,  contained 
17  per  cent,  of  fat. 

COMPOSITION  OF  FAT 

The  fats  occur  generally  in  the  form  of  triglycerides  of  various 
fatty  acids.  In  adipose  tissue  the  acids  are  chiefly  stearic,  palmitic, 
and  oleic,  the  consistency  of  the  fat  depending  on  the  relative  amount 
present  of  triolein,  with  its  low  melting-point.  In  certain  animals 
the  glycerides  of  more  unsaturated  fatty  acids  occur.  Thus  lard 
contains  about  10  per  cent,  of  fats  belonging  to  the  hnoleic  series. 
The  fats  of  cows'  milk,  though  consisting  chiefly  of  the  three  above 
mentioned,  include  also  the  esters  of  butyric  and  caproic  acids  in 
fair  amounts,  and  traces  of  the  intermediate  acids,  caprylic,  capric, 
lauric,  and  myristic  acids. 

The  '  fat  '  extracted  from  the  tissues  {e.g.  heart  muscle)  includes  a 
considerable  amount  of  '  phosphatides '  (lecithins,  &c.).  It  also 
contains  a  much  larger  proportion  of  unsaturated  fatty  acids,  of  the 
linoleic  and  even  lower  series,  so  that  its  '  iodine  value  '  is  generally 
found  relatively  high  (120  as  compared  with  40  to  60  in  adipose 
tissue). 

FUNCTIONS  OF  FAT 

First  and  foremost  must  be  mentioned  the  significance  of  fat  as  a 
reserve  food  store.  The  power  of  the  organism  to  store  up  reserve 
carbohydrate  is  strictly  limited.  The  liver  of  man  can  probably  not 
accommodate  more  than  150  grm.  of  glycogen,  and  assuming  that  the 
muscles  of  the  body  may  contain  an  equal  amount,  300  grm.  represents 
the  extreme  limit  of  storage  of  carbohydrates  in  the  body.  On  the 
other  hand,  in  most  animals  there  is  practically  no  limit  to  the  amount 
of  fat  which  can  be  laid  down,  and  over-feeding,  whether  with  carbo- 
hydrates or  fats,  leads  to  the  deposition  of  fat.  This  fat  does  not 
enter  into  the  normal  metabolism  of  the  body,  but  is  available  for 
use  whenever  the  needs  of  the  body  are  increased  above  its  income. 

As  to  the  part  taken  by  fat,  especially  the  hidden  fat  of  the  working 
cells,  in  the  chemical  processes  which  determine  the  life  of  the  cell, 
our  knowledge  is  still  very  scanty.  Fats  enter  into  the  constitution 
of  the  complex  bodies  lecithin  and  myelin,  which  form  important 
constituents  of  the  limiting  membrane  of  every  living  cell.  As  con- 
stituents of  the  membrane  itself,  fatty  substances  therefore  have  a 
protective  action,  and  also  regulate  the  passage  of  substances  into 
the  cell  across  the  membranes. 

The  presence  of  lecithin  as  an  integral  constituent  of  all  protoplasm, 
and  of  the  first  products  of  disintegration  of  protoplasm,  suggests 


886  PHYSIOLOGY 

that  this  substance  may  play  a  part  in  the  normal  transformations 
which  occur  within  the  cell,  and  may  represent,  so  to  speak,  the 
currency  into  which  fat  is  transformed  in  order  to  participate  in  the 
vital  processes,  and  that  it  is  in  this  form  that  the  energy  of  fat  is 
utilised  for  the  needs  of  the  cell. 

ORIGIN  OF  FAT  IN  THE  BODY 

Fat  formation  is  the  result  of  an  excess  of  income  over  expenditure. 
As  soon  as  the  latter  exceeds  the  former  the  fat  store  is  drawn  upon, 
so  that  adipose  tissue  is  the  one  which  presents  the  greatest  loss 
during  starvation.  As  much  as  97  per  cent,  of  the  total  fat  of  the  body 
may  disappear  during  this  process.  We  have  therefore  to  consider 
what  part  is  played  by  each  class  of  food-stuffs  in  the  formation  of 
fat.  Can  this  substance  be  formed  from  all  three  classes  of  food- 
stuffs ? 

FORMATION  FROM  THE  FAT  OF  THE  FOOD.  Experiment 
has  shown  that  the  composition  of  the  fat  of  any  animal  is  by  no 
means  constant  and  can  be  varied  within  wide  limits  by  alterations 
in  the  nature  of  the  fat  presented  in  the  food.  This  dependence 
of  the  composition  of  the  fat  on  the  fats  of  the  food  is 
shown  strikingly  in  an  experiment  performed  by  LebedefE.  Two 
dogs,  after  a  preliminary  period  of  starvation,  were  fed,  one  on  a 
diet  containing  a  large  amount  of  linseed  oil,  and  the  other  on  a  diet 
containing  much  mutton  suet.  After  some  weeks,  when  the  animals 
had  put  on  a  large  amount  of  fat,  they  were  killed,  and  it  was  found 
that  whereas  the  fat  of  the  dog  which  had  been  fed  on  mutton  suet  was 
solid  at  50°  C,  that  of  the  dog  fed  on  oil  was  still  fluid  at  0°  C.  It 
has  been  shown  moreover  that  by  feeding  animals  with  fatty  acids 
not  usually  found  in  the  body  these  are  laid  down  in  the  adipose  tissue. 
Thus  colza  oil  contains  a  glyceride  of  erucic  acid,  and  an  animal,  as 
Munk  has  shown,  fed  on  colza  oil  lays  on  fat  in  which  erucic  acid  is 
present.  The  same  physiologist  has  observed  that  after  the  adminis- 
tration of  various  fatty  acids  to  a  man  with  a  chylous  fistula,  the 
glycerides  of  the  corresponding  fatty  acids  made  their  appearance 
in  the  chyle,  whether  these  fatty  acids  were  those  normal  to  man 
or  consisted  of  substances,  such  as  erucic  acid,  not  generally  found  in 
human  fat.  One  must  conclude  therefore  that  the  fats  taken  with 
the  food,  if  not  immediately  required  for  the  energy  needs  of  the  body, 
are  laid  down  without  change  in  the  adipose  tissues,  as  well  as  in  the 
cells  of  the  body.  The  mechanisms  involved  in  the  translation  of 
fat  from  the  aUmentary  canal  to  the  tissues  are  of  the  simplest  possible 
description  and  only  involve  changes  of  hydrolysis  and  dehydrolysis. 
The  fats  are  hydrolysed  in  the  gut  and  are  resynthetised  to  a  certain 
extent  in  their  passage  into  the  epithehum.     In  the  chyle  and  blood 


THE  HISTORY  OF  FAT  IN  THE  BODY  887 

they  probably  wander  chiefly  as  neutral  fats,  to  be  rehydrolysed  for 
their  passage  into  the  cells  of  the  body,  which  they  may  enter  either 
in  the  form  of  soaps  or  possibly  as  fatty  acids  dissolved  in  some  of 
the  constituents  of  protoplasm. 

FORMATION  OF  FAT  FROM  CARBOHYDRATES.  It  has  long 
been  the  experience  of  farmers  that  animals  might  be  fattened  on 
a  diet  in  which  carbohydrates  predominate.  The  chemical  difficulty 
involved  in  the  transformation  of  carbohydrates  into  fats  has 
often  led  to  a  doubting  attitude  on  the  part  of  chemists  towards  this 
transformation.  Voib  put  forward  the  view  that  when  fats  are  formed 
in  the  body  as  a  result  of  an  excessive  carbohydrate  diet,  they  are 
formed,  not  directly  by  a  transformation  of  carbohydrate,  but  from 
the  proteins  of  the  food,  the  role  of  the  carbohydrates  of  the  food  being 
simply  to  protect  the  proteins  from  disintegration  and  oxidation,  so 
that  the  whole  of  their  carbon  can  be  utilised  for  the  formation  of  fat. 

Definite  evidence  has,  however,  been  brought  forward,  especially 
by  Lawes  and  Gilbert,  for  the  transformation  of  carbohydrates  into 
fats.  In  these  experiments  two  young  pigs,  ten  weeks  old,  of  the 
same  litter,  with  approximately  equal  weights,  were  taken.  One  was 
killed  and  the  fat  and  total  nitrogen  in  the  body  estimated.  From  the 
amount  of  nitrogen  the  maximum  possible  quantity  of  proteins  present 
was  calculated.  The  second  was  fed  on  barley  for  four  months.  The 
barley  was  measured  and  analysed,  as  well  as  the  amount  of  undigested 
fat  and  protein  that  passed  through  the  animal.  At  the  end  of  the 
four  months  the  second  animal  was  killed  and  analysed.  It  was  found 
that  the  animal  contained  TSG  kilos  more  protein  and  8'6  kilos  more 
fat.  It  had  taken  up  with  the  food  7 '49  kilos  more  protein  and 
0*66  kilo  fat.  If  we  subtract  the  protein  added  to  the  body  (TSG) 
from  that  taken  up  with  the  food  (7"49)  there  is  a  remainder  of  5'93 
kilos  which  might  possibly  have  given  rise  to  fat.  But  7'9  kilos  of 
fat  had  been  added  in  the  body — a  far  larger  amount  than  could 
possibly  have  arisen  from  the  maximum  amount  of  protein  left  over 
for  the  purpose.  At  least  5  kilos  of  fat  in  this  experiment  must  have 
been  derived  from  the  direct  conversion  of  the  carbohydrates  of  the 
food.  We  must  conclude  that  fat  can  be  formed  directly  from  carbo- 
hydrates, although  how  and  where  this  conversion  takes  place  is  at 
present  quite  unknown.  The  fats  formed  on  a  carbohydrate  diet  are 
deposited  chiefly  in  the  subcutaneous  tissue.  For  the  reasons  already 
given  the  liver  is  found  free  from  fat  under  these  conditions.  In  the  fat 
formed  from  carbohydrate  the  two  saturated  acids,  palmitic  and  stearic 
acid,  predominate.  On  this  account  the  fat  has  a  firm  consistency  and 
a  high  melting-point.  The  fats  of  low  melting-point,  such  as  olein, 
are  absorbed  more  readily  from  the  intestine  than  those  of  high 
melting-point.     Where  the  fat  of  the  body  is  rliiofly  derived  from  the 


888  PHYSIOLOGY 

fat  of  the  food  it  tends  to  be  of  the  more  fluid  acids  and  contains  a 
larger  percentage  of  olein. 

Although  it  is  impossible  to  trace  out  all  the  steps  in  the  process 
of  conversion  of  sugar  into  fatty  acid,  we  are  acquainted  with  certain 
reactions  which  may  throw  some  light  on  the  nature  of  the  changes 
involved.  If  we  compare  the  formula  of  dextrose  with  that  of  the 
corresponding  fatty  acid,  caproic  acid, 

CHg  CH2OH 

CH2  CHOH 

I  I 

CH2  CHOH 

CH2  CHOH 

CH2  CHOH 

COOH  CHO 

we  see  that  the  conversion  involves  a  considerable  loss  of  oxygen.  In 
order  to  convert  three  molecules  of  glucose,  C6H12O6,  into  one  molecule 
of  stearic  acid,  C18H36O2,  it  is  necessary  to  split  off  16  atoms  of  oxygen. 
That  this  setting  free  of  oxygen  actually  occurs  in  the  transformation 
of  carbohydrate  into  fat  is  shown  by  the  study  of  the  respiratory 
exchanges  of  animals  which  are  rapidly  laying  on  a  store  of  fat  at 
the  expense  of  a  carbohydrate  food.  Thus  the  marmot,  towards  the 
end  of  summer,  eats  large  quantities  of  carbohydrate  food  and  very 
rapidly  lays  on  a  thick  layer  of  subcutaneous  fat  to  last  it  during  the 
winter.  If  glucose  were  entirely  oxidised  in  the  body  the  amount  of 
oxygen  absorbed  would  be  exactly  equal  to  the  amount  of  carbon 
dioxide  evolved.  Thus  CgHiaOg  +  GOo  =  6CO2  +  6H2O. 
In  this  case  the  respiratory  quotient  would  be 

6C0, 


60, 


=  1 


If,  however,  oxygen  is  being  set  free  by  the  conversion  of  part  of 
the  carbohydrate  into  fat,  this  oxygen  will  be  available  for  the  oxida- 
tion of  other  portions  of  the  carbohydrate.  The  animal  will  not  need 
to  take  in  so  much  oxygen  from  outside  for  the  production  of  the  same 
amount  of  carbon  dioxide,  and  the  carbon  dioxide  output  of  the  animal 
will  therefore  be  greater  than  its  oxygen  intake.  Pembrey  has  shown 
that  under  these  conditions  the  respiratory  quotient  may  be  as  high  as 
1-5.  We  cannot  assume,  however,  that  the  process  of  conversion  of 
glucose  into  fatty  acids  takes  place  by  this  simple  process  of  deoxidation. 


THE  HISTORY  OF  FAT  IN  THE  BODY  889 

The  change  is  probably  a  more  complex  one,  and  occurs  in  separate 
stages.  Glucose  easily  breaks  up  under  the  action  of  ferments  into  two 
molecules  of  lactic  acid,  and  lactic  acid  can  be  equally  easily  converted 
into  aldehyde  and  formic  acid,  thus  : 

CgHiaOc  =  2C3HCO3  lactic  acid,  and 
CH3 

I  CH3        H 

CHOH=     I       +   I 
I  OHO       COOH 

CHOH 
Now  aldehydes  possess  a  marked  tendency  to  combine  with  other 
molecules  of  other  or  the  same  substance,  i.e.  to  undergo  polymerisa- 
tion.    Thus  from  two  molecules  of  lactic  acid  we  get  one  molecule 
of  aldol. 

CH3 

CH3  CHOH 

CHO  CH2 

OHO 

which  by  a  simple  transposition  of  oxygen  would  give  butyric  acid, 
or  by  oxidation  would  give  ^-oxybutyric  acid,  a  substance  which 
occurs  during  various  abnormal  conditions  of  metabolism. 

The  fats  occurring  in  the  body,  e.cj.  in  milk,  include  only  the 
fatty  acids  with  an  even  number  of  carbon  atoms  {v.  p.  60).  We 
may  probably  assume  from  this  fact  that  the  building  up,  as  well 
as  the  breaking  down,  of  fatty  acids  occurs  by  two  carbon  atoms 
at  a  time.  Although  heating  aldehyde  or  aldol  with  potash  or  any 
other  polymerising  agent  gives  rise  to  a  mixture  of  many  substances, 
it  is  probable  that  under  the  catalytic  agencies  at  the  disposal  of 
the  living  cell  these  synthetic  changes  are  directed  entirely  in  one 
direction,  so  that  from  butyric  acid  we  shall  have  hexoic,  caprylic, 
capric  acid,  and  so  on.  Why  the  process  comes  to  an  end  with  the 
formation  of  the  1(5  and  18  carbon  atoms  it  is  difficult  to  see.* 
Possibly  with  the  formation  of  acids  whose  melting-point  is  higher 
than  that  of  the  body  temperature,  a  certain  stability  is  imparted 
to  them  which  prevents  their  further  circulation  and  ready  synthesis 
to  the  still  higher  acids. 

With  regard  to  the  glycerine  which  is  a  necessary  constituent 
of  the  neutral  fats  laid  down  in  the  bod}',  there  is  no  difficulty  in 

*  From  tho  fats  extracted  from  the  kidney  Dunham  hasisolatt-d  eanian>)ic 
acid,  C24H48O2. 


890  PHYSIOLOGY 

accounting  for  its  formation  from  the  carbohydrates.     By  a  simple 
splitting  of  glucose,  we  may  obtain  two  molecules  of  glyceraldehyde, 

CH2OH 

I 
CHOH 

(JHOH 

I 
OHOH 

CHOH 


CH2OH 

I 
=    2  CHOH 

I 
CHO 


CHO 

which    by   reduction   is   readily   converted   into   the    corresponding 
alcohol  glycerine,  CH2OH.CHOH.CH2OH. 

We  may  conclude  then  that  fats  are  formed  by  the  body  with 
ease  from  carbohydrates,  and  that  in  all  probability  this  change 
involves  a  building  up  of  the  fatty  acid  from  the  lower  members 
of  the  successive  addition  of  a  group  containing  two  atoms  of  carbon. 
The  whole  change,  as  Leathes  has  shown  [v.  p.  134),  is  an  exothermic 
one.  For  the  formation  of  one  molecule  of  palmitic  acid,  four  mole- 
cules of  glucose  would  be  required,  and  12-5  per  cent,  of  the  total 
energy  of  the  glucose  would  be  set  free  as  heat. 

THE  FORMATION  OF  FAT  FROM  PROTEINS.  Among  the 
decomposition  products  of  proteins  the  amino-derivatives  of  the 
fatty  acids  take  a  prominent  part.  It  would  seem  therefore  highly 
probable  that  by  a  process  of  deamination  these  amino-acids  should 
be  first  converted  into  fatty  acids,  which  in  their  turn  would  be  built 
up  by  the  process  we  have  just  discussed  into  the  higher  members 
of  the  series.  For  many  years,  as  a  result  of  the  investigations  of 
Voit,  the  proteins  were  indeed  regarded  as  the  chief,  if  not  the  sole, 
source  of  the  fats  of  the  body,  and  it  needed  the  energetic  assaults 
of  Pfiiiger  on  this  doctrine,  in  1891,  before  it  could  be  clearly 
examined  by  physiologists. 

Let  us  see  what  are  the  grounds  for  assuming  a  formation  of  fat 
from  protein.  In  the  first  place,  there  is  a  well-known  experiment 
by  Voit.  A  dog  was  fed  with  large  quantities  of  lean  meat  for  a 
considerable  time.  Voit  found  that  the  whole  of  the  nitrogen  of  the 
intake  was  excreted,  but  that  a  certain  percentage  of  carbon  was 
retained  in  the  body,  and  that  the  percentage  of  this  carbon  was 
greater  than  could  be  accounted  for  by  the  deposition  of  glycogen 
in  the  liver  and  muscles.  He  therefore  assumed  that  it  must  have 
been  laid  down  as  fat.     Pfiiiger  showed  that  these  conclusions  were 


THE  HISTORY  OF  FAT  IN  THE  BODY  891 

not  justified  by  Voit's  results,  and  were    really   based  on  the  fact 
that  too  high  a  figure  had  been  assumed  for  the  carbon  of  the  meat. 
Whereas  Voit  found  that  the  animal  had  laid  on  50  grm.  of  fat  during 
one  day  of  the  experiment,  a  recalculation  of    the  same  results  by 
Pfluger  shows  that  the  animal  could    not  have  put  on  more  than 
3-9  grm.  of    fat,  an  amount  which  might  quite  well  be  accounted 
for  by  the  fat  and  glycogen  present  in  the  meat.    Pfluger  has  shown 
moreover  that  an  animal  may  be  fed  for  weeks  on  the  leanest  meat 
that  it  is  possible  to  procure,  in  any  quantities,  without  putting  on 
any  fat  at  all,  and,  as  we  have  seen,  increasing  the  ration  of  protein 
increases  simply  the  nitrogenous  and  general  metabolism  of  the  body. 
Although  therefore  we   must  assume  that  the  healthy  body  does 
not  normally  form  fat  from  protein,  there    are  certain  pathological 
conditions  which  seem  at  first  to  tell  in  favour  of  such  a  conversion. 
Thus  during  certain  diseases,  such  as  diphtheria,  pernicious  anajmia, 
and  as  the  result  of   poisoning  by  phosphorus,  the  majority  of  the 
organs  of  the   body  undergo  acute  fatty  degeneration.      The  liver 
may  be  enlarged  and  all  its  cells  are  studded  with  fat  granules  which 
are  apparently  formed   by  a  change  in  the  protoplasm  of  the  cells. 
This  change  was  long   interpreted  as  due  to  a  direct  conversion  of 
protein  into  fat.    More  exact  analyses  have  shown  that  during  fatty 
degeneration  the  total  fat  in  the  body  is  not  increased.     Thus  one 
observer  took  124  pairs  of  frogs  and  poisoned  one  of  each  pair  with 
phosphorus.     The  animals  were  then  killed,  and  the  whole  of  them 
analysed.    The  difierence  in  the  content  of  fat  between  the  poisoned 
and  unpoisoned  animals  fell  within  the  limits  of  experimental  error,  so 
that  there  had  been  no  increase  in  the  fat  of  the  body  as  the  result  of 
the  poisoning.    In  some  of  these  cases  the  liver  is  actually  enlarged, 
but  this  deposition  of  fat  in  the  cells  is  due  to  the  immigration  of  the 
fat  from  other  parts  of  the  body  and  not  to  conversion  of  the  protein 
ot  the  cells.      This  is  shown  by  the  facts  that  the  composition  of  the 
fat  in  the  degenerated  liver  varies  according  to  the  composition  of  the 
fat  in  the  rest  of  the  body,  and  that,  if  abnormal  fats  are  given  with 
the  food,  such  as  erucic  acid  or  iodine  fats,  these  are  found  in  the  fat 
extracted  from  the  liver.     In  fatty  degeneration  two  processes  are 
at  work  :    one  is  the  immigration  of    fats  from  other  parts  of  the 
body  ;   the  second,  and  probably  the  more  important  one,  is  a  change 
in  the  relation  of  the  fat  to  the  protoplasm  of  the  cell. 

It  was  long  stated  that  the  fat  of  milk  was  not  increased  by  feeding 
with  fats,  but  only  by  feeding  with  proteins.  More  recent  researches 
have  given  contrary  results.  The  dependence  of  the  composition 
of  milk  fat  on  the  composition  of  the  fat  present  in  the  body  or 
administered  in  the  food  is  shown  by  the  fact  that  cows  fed  ou  oil- 
cake may  produce  a  butter  which  is  useless  for  commercial  purposes 


892  PHYSIOLOGY 

owing  to  its  low  melting-point.  In  one  experiment,  when  a  cow 
was  fed  on  linseed  oil,  the  iodine  nimiber  of  the  milk  fat  rose  from 
30,  its  normal  figure,  to  70-4.  After  the  introduction  of  iodine  fat 
subcutaneously,  iodine  fats  are  found  in  the  milk.  In  another 
experiment  a  bitch  which  had  been  fed  with  mutton  suet  and 
had  deposited  in  its  tissues  a  fat  of  high  melting-point  produced 
a  milk  the  iodine  number  of  which  was  the  same  as  that  of 
the  mutton  suet.  In  this  case  the  fat  of  the  milk  had  evidently 
been  derived  from  the  tissues,  since  during  the  lactation  the  animal 
was  being  fed  on  meat  which  was  poor  in  fat.  The  same  dependence 
of  fatty  secretion  on  diet  has  been  found  in  geese,  where  the  com- 
position of  the  oil  secretion  of  the  feather  glands  has  been  altered 
by  giving  abnormal  fats,  such  as  sesame  oil,  with  the  food. 

We  must  conclude  that  the  protein  of  the  food  cannot  give  rise 
to  fat  in  the  body.  A  nearer  consideration  of  the  composition  of  the 
proteins,  taken  in  connection  with  our  discussion  as  to  the  mechanism 
by  means  of  which  the  fat  is  built  up  in  the  body,  might  help  to  account 
for  this  fact.  The  fatty  acids  formed  by  the  disintegration  of  proteins 
are  chiefly  the  lower  acids  of  the  series,  such  as  acetic  and  propionic, 
which  would  undergo  rapid  oxidation  in  the  body.  Butyric  acid 
has  not  yet  been  found  among  the  products  of  disintegration  of 
the  proteins,  and  the  6-carbon  acid,  derived  from  leucin,  is  not 
the  normal  acid,  but  is  a  branched  chain,  viz.  isobutyl-acetic  acid. 
The  one  acid  therefore  from  which  the  long  normal  chain  of  the 
fatty  acids  might  be  built  up,  namely,  butyric  acid,  is  conspicuous 
by  its  absence,  and  there  is  thus  no  starting-point  among  the 
products  of  disintegration  of  the  protein  molecule  which  might  serve 
for  the  synthesis  of  the  fats  of  the  body. 

THE  UTILISATION  OF  FATS  IN  THE  BODY 
The  constant  presence  of  fat,  and  bodies  alhed  to  fat,  in  proto- 
plasm, from  whatever  source  obtained,  suggests  that  these  substances 
can  enter  directly  into  the  chemical  changes  on  which  the  life  of  the 
cell  depends  and  that  they  play  an  essential  part  in  vital  phenomena. 
The  direct  utihsation  of  fat  for  the  needs  of  the  body  is  also 
indicated  by  the  results  of  experiments  on  man  and  the  lower  animals. 
After  a  few  days'  starvation  the  body  may  be  regarded  as  practically 
free  from  stored  carbohydrate.  The  sole  source  of  the  energy  which 
is  evolved  under  these  circumstances  must  be  fats  and  proteins, 
and  it  is  possible  to  determine  by  an  estimation  of  the  nitrogen 
output  the  exact  fraction  of  the  total  energy  evolved  which  is  to  be 
ascribed  to  protein  metabolism.  Thus  in  the  case  of  Cetti,  the 
professional  faster,  it  was  found  that  the  nitrogenous  metabolism 
per  unit  of  body  weight  remained  fairly  constant  between  the  fifth 


THE  HISTORY  OF  FAT  IN  THE  BODY 


893 


and  tenth  days  of  starvation,  and  corresponded  to  an  average  of 
1  grm.  of  protein  per  kilo  body  weight  daily.  In  order  to  convert 
this  amount  of  protein  into  urea,  carbonic  acid,  sulphuric  acid, 
and  water,  nearly  2  grm.  of  oxygen  would  be  required  in  the 
twenty-four  hours,  i.e.  about  1  c.c.  per  minute.  Cetti's  total 
oxygen  consumption  was  at  the  rate  of  5  c.c.  per  kilo  per  minute, 
so  that  four-fifths  of  the  oxygen  absorbed  was  required  for  the 
oxidation  of  non-nitrogenous  substances,  and  these,  as  we  have 
seen,  could  only  have  been  fats.  In  animals  with  a  large  store 
of  fat  the  proportion  of  the  energy  obtained  at  the  cost  cf  the  fats 
may  be  still  greater.  In  dogs  Rubner  and  Voit  reckoned  that  only 
10  to  16  per  cent,  of  the  total  energy  was  derived  from  proteins,  the 
rest,  i.e.  84  to  90  per  cent.,  being  obtained  from  the  oxidation  of  fats. 

The  oxidation  of  fats  supplies  energy  not  only  for  the  production 
of  heat  but  also  for  the  performance  of  mechanical  work,  and  it 
seems  probable  that  the  utihsation  of  the  fat  occurs  in  the  muscular 
tissues  themselves.  Fat  is  found  as  a  normal  constituent  of  all 
muscle  fibres,  and  the  amount  of  this  substance  is  greater  in  propor- 
tion to  the  activity  of  the  muscles  concerned.  Thus  the  ever-active 
heart  muscle,  and  the  red  muscles  of  the  diaphragm,  contain  larger 
amounts  of  fat  than  the  pale  voluntary  muscles  which  only  have  to 
undertake  short  periods  of  activity.  In  the  human  heart  muscle 
15  per  cent,  of  the  sohds  are  soluble  in  ether,  and  more  than  one- 
half  of  the  ether  extract  is  composed  of  fat,  and  is  sufficient  to  supply 
the  energy  of  the  contracting  heart  for  six  or  seven  hours'  work. 

The  degree  to  which  the  muscles  during  contraction  call  upon 
each  class  of  food-stuffs  may  be  judged  from  the  respiratory  quotient 
which,  as  we  have  seen  in  an  earlier  chapter,  is  unaffected  by  muscidar 
work.  If  the  body  has  previously  supplied  the  greater  part  of  its 
needs  at  the  expense  of  fats,  it  will  continue  to  do  so  during  muscular 
work.  This  is  well  shown  in  the  following  Table,  in  which  the  oxygen 
consumption  and  respiratory  quotient  are  compared  in  a  man  resting 
and  working  on  three  different  diets,  one  principally  fat,  one  prin- 
cipally carbohydrate,  and  the  other  principallv  protein  : 


Diet, 
priiicipiiliy 

Resting 

Working 

m.  kg.  of 
work  done 

Per  m.  kg.  of  work 

c.c.  oxy- 
gen used 
per  min. 

llcsp. 
quo- 
tient 

c.c.  oxygen 

U.sed  per 

mill. 

Rcsp. 
quo- 
tient 

c.c.  oxy- 
gen used 

lul. 

Fat      . 

Carboliydratc 

IVotoiit 

319 
277 
306 

0-72 
0«)() 
O-SO 

1029 
1(129 
1127 

0-72 
()-90 

0-S(> 

3.^>4 
34(1 
34.") 

2(»1 
21 7 
2-3S 

9-39 
10-41 
1 1  -3.^ 

894  PHYSIOLOGY 

We  may  conclude  then  that  the  tissues  of  the  body  are  able  to 
obtain  their  energy  by  the  direct  utiUsation  of  the  fats  which  they 
contain.  The  changes  in  the  fat  molecules  which  are  involved  in  the 
utilisation  of  their  energy  are  still  to  be  determined.  The  energy  of  fat 
is  only  available  on  its  oxidation.  The  transformation  of  fats  into  fatty 
acids  or  glycerine,  or  the  synthesis  of  fats  from  aldehydes  or  from  carbo- 
hydrates, which  we  have  discussed  in  the  previous  section,  do  not 
involve  any  large  changes  of  energy.  Weight  for  weight,  butyric  acid 
with  its  4  carbon  atoms  has  practically  the  same  heat- value  as  stearic 
acid  with  its  18  carbon  atoms,  or  stearine  with  its  57  carbon  atoms.  We 
have  therefore  to  determine  what  changes  the  great  fat  molecule 
undergoes  before  it  is  brought  into  a  condition  in  which  it  may 
undergo  oxidation  and  set  free  the  energy  required  for  the  purposes  of 
the  body.  The  general  tendency  of  metabolic  research  of  recent  years 
is  to  show  that  the  Uving  cell  is  in  a  position  to  effect  all  changes 
which  do  not  involve  a  large  evolution  or  absorption  of  energy  in 
either  direction.  In  the  plant  cell,  at  any  rate,  the  fatty  acids  may  be 
converted  into  amino-acids,  or  the  latter  may  be  deaminised,  as  occurs 
in  the  walls  of  the  gut,  into  fatty  or  oxyacids.  Dextrose  may  pass  into 
maltose,  and  glycogen  into  starch,  or  starch  may  be  converted  into 
maltose  or  dextrose.  If  therefore  fats  are  constantly  being  made  from 
carbohydrates,  or  from  the  lower  molecules  such  as  aldehyde,  by  a 
process  of  repeated  addition  of  a  group  containing  two  carbon  atoms, 
it  is  probable  that  the  same  change  will  go  on  in  a  reverse  direction 
when  fats  are  broken  down  previous  to  oxidation. 

In  the  germination  of  oily  seeds  the  utihsation  of  the  fat  is  pre- 
ceded by  the  spHtting  of  the  higher  fatty  acids  into  acids  of  lower 
molecular  weight.  Although  we  cannot  trace  out  in  the  animal 
body  the  stages  in  the  breakdown  of  a  large  fatty  acid,  such  as  stearic 
acid,  we  can,  by  a  certain  artifice  much  used  in  metabolic  experi- 
mentation, bring  forward  evidence  in  favour  of  the  view  that  the 
breakdown,  like  the  building  up  of  fats,  occurs  by  two  carbon  atoms 
at  a  time.  When,  in  the  process  of  breaking  down,  a  fat  finally 
arrives  at  the  four-  or  two-carbon  stage,  it  is  quickly  oxidised  and  is 
therefore  not  traceable  in  the  excretions  or  in  the  fluids  of  the  body. 
This  end  stage  may,  however,  be  preserved  from  oxidation  by  hanging 
it,  so  to  speak,  on  to  an  aromatic  ring.  If  acetic  acid  or  ethyl  alcohol 
be  administered  in  small  quantities,  it  is  entirely  oxidised.  If, 
however,  these  bodies  be  attached  to  a  benzene  ring  and  be  adminis- 
tered as  a  phenacetic  acid  or  phenyletbyl  alcohol,  they  are  excreted 
in  the  oxidised  form  of  phenaceturic  acid,  which  is  simply  a  combina- 
tion of  phenacetic  acid  with  glycine.  In  the  same  way  benzoic  acid 
and  benzyl  alcohol  are  excreted  in  the  form  of  hippuric  acid,  thus  : 

Phenacetic    acid,   CgHs.CHgCOOH,   is    excreted    as    CgHs.CHg.- 


THE  HISTORY  OF  FAT  IN  THE  BODY  895 

CO .  NH .  OH2COOH.  In  each  case  the  fatty  side-chain  is  protected 
from  further  oxidation  by  its  attachment  to  the  benzene  ring  and 
by  the  tacking  on  of  the  glycine  molecule. 

With  phenylpropionic  acid  two  carbon  atoms  of  the  side-chain 
are  oxidised,  and  the  remaining  benzoic  acid  excreted  as  hippuric 
acid.  Phenylbutyric  acid  undergoes  a  similar  change  ;  two  carbon 
atoms  are  oxidised  away,  leaving  phenylacetic  acid,  which  is  excreted 
as  phenylaceturic  acid.  If  phenyl  valerianic  acid  be  given,  four  carbon 
atoms  are  oxidised  away  and  benzoic  acid  is  left,  and  appears  in  the 
urine  as  hippuric  acid.  In  each  case  the  oxidation  of  the  side-chain 
occurs  by  two  carbon  atoms  at  a  time,  and  it  seems  probable  that  a 
similar  change  will  occur  in  the  ordinary  fatty  acid,  the  last  stages,  in 
the  absence  of  any  protective  ring  compound,  being  oxidised  like  the 
earlier  groups  and  therefore  not  detectable  in  the  excretions. 

Evidence  in  the  same  direction  is  afforded  by  certain  cases  in 
which  the  oxidative  power  of  the  body  for  fats  is  inadequate,  either 
by  reason  of  morbid  changes  in  the  oxidative  powers  of  the  body, 
or  as  the  result  of  what  we  may  call  an  overstrain  of  the  fat- 
oxidising  powers.  Such  a  condition  is  found  in  the  acetonuria 
of  acute  acidosis,  such  as  occurs  in  the  end  stages  of  diabetes. 
The  oxybutyric  and  diacetic  acids  occurring  in  the  urine  in  this 
condition  were  formerly  thought  to  be  derived  from  the  carbo- 
hydrates of  the  food,  or  from  sugar  abnormally  produced  in  the 
body.  The  condition  of  acidosis,  however,  is  often  brought  on  directly 
as  the  result  of  putting  the  patient  on  a  strict  anti-diabetic  diet,  i.e. 
one  consisting  chiefly  or  exclusively  of  fats  and  proteins,  and  mav 
be  produced  in  a  healthy  man  by  simple  starvation,  when  the  body 
has  only  at  its  disposal  its  stored-up  fats  and  proteins.  It  occurs 
in  a  marked  degree  on  the  administration  of  a  diet  consisting  almost 
entirely  of  fats.  Thus  in  one  experiment  a  healthy  man  took  as 
his  sole  diet  for  five  days  a  daily  ration  of  250  grm.  of  butter,  200  grm. 
of  oil,  and  a  httle  wine.  The  result  was  an  intense  acidosis,  such 
as  is  only  found  in  the  severest  cases  of  diabetes,  diacetic  acid,  oxy- 
butyric acid,  and  acetone  being  found  in  the  urine  in  large  c^uantities. 
On  the  last  day  of  the  experiment  these  acids  caused  so  much  of  the 
nitrogen  in  the  urine  to  appear  as  ammonia  that  of  the  5-8  grm.  total 
nitrogen  excreted  only  2-7  grm.  were  in  the  form  of  urea,  while  as 
much  as  2*1  grm.  were  present  as  ammonia. 

If,  during  a  period  of  starvation  in  man,  a  day  is  interpt)Iated 
on  which  100  grm.  of  protein  are  taken,  the  amount  of  acetone  excreted 
falls  below  that  obtained  on  the  other  days  when  the  individual 
is  living  chiefly  at  the  cost  of  his  own  fat.  These  facts  indicate 
that  the  sole  source  of  the  /^-oxybutyric  acid  and  the  diacetic 
acid   is   the   fats   of   the   food   or  of   the   body.     The   condition   of 


896  PHYSIOLOGY 

acidosis  is  more  easily  brought  about  by  ingestion  of  butyric 
acid  than  of  the  higher  acids,  such  as  palmitic  or  stearic,  suggest- 
ing that  whatever  fatty  acid  is  given  it  is  finally  reduced  to 
butyric  acid  before  its  oxidation,  and  that  in  the  condition  of  acidosis 
it  is  merely  the  last  stages  of  this  oxidation  which  are  at  fault.  We 
are  thus  justified  in  concluding  that  the  oxidative  breakdown  of 
fats  occurs  always  by  an  oxidation  in  the  /5  position. 
We  take,  for  instance,  the  6-carbon  stage  : 

CH3 .  CH2 .  CH2 .  CH2 .  CH2 .  COOH 

the  first  change  which  probably  occurs  is  the  oxidation  : 

CH3 .  CH2 .  CH2 .  CH2OH .  CH2 .  COOH 

A  further  change  is  the  complete  oxidation  of  the  last  two  groups 
and  the  production  of  butyric  acid  : 

CH3.CH2.CH2.COOH 

This  then   undergoes  again  oxidation  in  the  ft  position,  with    the 
production  of  ^-oxybutyric  acid  : 

CH3.CHOH.CH2.COOH 

and  then  again  is  converted  to  diacetic  acid, 

CH3.CO.CH2.COOH 

In  the  normal  individual  this  last  stage  undergoes  complete 
oxidation,  both  oxybutyric  acid  and  diacetic  acid  given  to  a  healthy 
person  being  completely  destroyed  in  the  body.  It  is  only  under 
the  abnormal  conditions  which  we  have  mentioned  above  that  these 
last  stages  fail  of  complete  oxidation,  and  are  excreted  unchanged  in 
the  urine. 

THE  QUESTION  OF  THE  FORMATION  OF  SUGAR  FROM  FAT 

The  ease  with  which  the  animal  body  performs  the  difficult  chemical 
operation  of  transforming  carbohydrate  into  fat  suggests  that  under 
appropriate  conditions  it  might  effect  the  reverse  change.  Is  there 
any  evidence  that  in  the  animal  body  sugar  may  be  derived  from 
fat  ?  Such  a  conversion  is  of  normal  occurrence  during  the  ger- 
mination of  fatty  seeds,  starch  sugar  and  cellulose  being  formed  at 
the  expense  of  the  stored-up  fats  of  the  seeds.  If  such  seeds  be  allowed 
to  germinate  over  mercury  in  a  confined  volume  of  oxygen,  they 
are  found,  like  seeds  containing  chiefly  carbohydrate  reserves,  to 
absorb  oxygen  and  to  give  off  carbon  dioxide.  Whereas,  however,  in 
the  latter  case  the  amount  of  carbon  dioxide  evolved  is  almost  equal 
to  the  oxygen  absorbed,  in  the  case  of  the  fatty  seeds  much  less 


THE  HISTORY  OF  FAT  IN  THE  BODY  897 

carbon  dioxide  is  given  out  than  would  correspond  to  the  volume 
of  oxygen  absorbed,  so  that  the  total  volume  of  gas  above  the  seeds 
diminishes. 

The  same  change  in  the  relation  of  oxygen  intake  to  carbon  dioxide 
output  is  found  under  certain  conditions  in  animals.  During  hiberna- 
tion, as  Pembrey  has  shown,  the  marmot  has  a  very  low  respiratory 
quotient,  which  may  be  not  greater  than  0-3  or  04.  This  means  that 
the  animal  takes  in  more  oxygen  than  the  carbon  dioxide  which  it  gives 
out,  and  this  intake  of  oxygen  can  be  so  marked  as  to  cause  an  appre- 
ciable increase  in  the  weight  of  the  animal,  which  under  such  cir- 
cumstances is  literally  living  on  air.  This  retention  of  oxygen  can 
only  be  explained  by  assuming  that  there  is  a  conversion  of  sub- 
stances containing  a  small  amount  of  oxygen  into  substances  containing 
a  larger  amount  of  oxygen  going  on  in  the  body,  such  a  conversion 
as  that  of  fats  into  carbohydrates.  Just  as  the  high  respiratory 
quotient  obtained  from  a  marmot  during  the  period  of  putting  on 
fat  was  shown  to  be  associated  with  a  conversion  of  carbohydrate 
into  fat,  so  does  the  abnormally  low  quotient  obtained  during  hiber- 
nation indicate  the  reverse  change  of  fat  into  carbohydrate. 

The  same  conversion  has  been  alleged  to  take  place  in  certain 
cases  of  diabetes.  In  many  cases  when  the  diabetic  animal  is  living 
on  a  purely  protein  diet,  a  uniform  ratio  has  been  found  to  exist 
between  the  glucose  or  dextrose  and  the  nitrogen  excreted. 

—  equals  generally  2-8. 

In  certain  other  cases  a  constant  D  :  N  ratio  of  3-65  has  been  found. 
The  former  represents  a  conversion  of  45  per  cent.,  the  latter  of 
58  per  cent.,  of  protein  into  sugar.  In  a  few  cases,  however,  even 
during  complete  starvation,  the  ratio  D  :  N  has  been  found  to  be  much 
greater  than  that  given  above  and  to  amomit  to  as  much  as  10  or  12. 
These  animals  are  stated  to  be  practically  free  from  carbohydrates,  so 
that  the  sugar  excreted  in  the  urine  can  only  come  from  the  breakdown 
of  proteins  or  fats.  It  is  impossible  by  any  means  whatever  to  break 
up  a  protein  molecule  so  as  to  get  from  it  ten  times  as  much  dextrose 
as  corresponds  to  the  nitrogen,  and  Pfliiger  concludes  that  in  cases 
where  such  a  high  D  :  N  ratio  exists  the  dextrose  must  have  been 
derived  by  a  conversion  of  the  fats  of  the  body.  This  conclusion 
is  by  no  means  generally  accepted.  If  correct,  it  would  bear  out 
the  general  statement  made  above,  namely,  that  in  the  living  body 
practically  all  the  chemical  changes  are  reversible,  and  that  the 
living  cell  can  so  regulate  the  conditions  of  the  reaction  that  the 
reversible  reaction  becomes  practically  complete  in  either  direction, 
the  direction  being  determined  by  the  needs  of  the  body  at  the  time. 


898  PHYSIOLOGY 

Accepting  this  generalisation,  the  chemical  mechanism  by  which 
fats  are  converted  into  carbohydrates  must  be  the  reverse  of  that 
by  which  carbohydrates  are  changed  into  fats.  The  2-carbon  gToiip 
split  off  from  the  large  fatty  molecules  are  probably  utilised  for  the 
building  up  of  the  sugar  molecule.  We  know  that  such  a  synthesis 
can  take  place  from  such  simple  groups  as  formic,  glycollic,  or  glyceric 
aldehyde.  Though  it  is  impossible  to  deny  to  any  cell  of  the  body  the 
power  of  effecting  the  conversion  of  fats  into  carbohydrates,  or  carbo- 
hydrates into  fats,  the  chief  centre  for  such  conversions  is  probably 
the  chemical  factory  of  the  body,  namely,  the  liver.  It  is  significant 
that  in  the  course  of  fatal  diabetes,  in  which  the  fat  disappears  entirely 
from  the  body,  and  there  is  wasting  of  practically  all  the  tissues, 
the  hver  is  the  only  organ  which  retains  its  weight  unchanged.  During 
this  disease  there  has  been  an  enormous  amount  of  work  done  in  the 
conversion  of  proteins  and  possibly  of  fats  into  carbohydrates  which 
could  not  be  utilised  by  the  body,  and  the  large  size  of  the  liver  at 
death  suggests  that  the  work  of  transformation  has  been  performed 
by  this  organ. 


SECTION  IV 

THE  METABOLISM  OF  CARBOHYDRATES 

All  the  carbohydrates  which  are  taken  in  with  the  food  are 
ultimately  transformed  in  the  alimentary  tract,  or  in  its  walls,  into 
the  three  monosaccharides,  glucose,  fructose,  and  galactose.  These 
three,  together  with  mannose,  are  the  only  sugars  which  are  directly 
fermentable  and  directly  assimilable  by  higher  animals.  A  con- 
sideration of  their  structural  formulae  shows  that  they  are  fairly 
easily  interconvertible,  galactose  presenting  the  greatest  differences 
from  the  general  type.  This  conversion  actually  takes  place  in  watery 
solution.  If  a  solution  of  any  one  be  left  for  some  months,  it  will  be 
found  to  contain  the  representatives  of  all  four. 

Since  these  monosaccharides,  for  the  greater  part  glucose,  must 
enter  the  blood  in  large  quantities  during  the  absorption  of  a  heavy 
carbohydrate  meal,  one  would  expect  to  find  a  greater  proportion 
in  the  blood  during  such  a  meal  than  during  a  period  of  starvation. 
The  amount  of  reducing  sugar  in  the  blood,  however,  is  practically 
constant,  and  varies  between  0-1  and  0-15  per  cent. 

Searching  for  the  origin  of  this  constant  proportion  of  reducing 
sugar,  Claude  Bernard  found  that  the  blood  of  the  hepatic  vein  in  a 
fasting  animal  contained  more  sugar  than  the  blood  taken  at  the 
same  time  from  the  portal  vein.  Although  the  rehabihty  of  this 
experimental  result  has  been  put  in  doubt  by  more  recent  investigators, 
it  was  important  in  that  it  attracted  Bernard's  attention  to  the  Uver. 
If  the  liver  be  taken  from  an  animal  which  has  been  dead  for  some 
time,  and  extracted  with  water,  the  extract  is  found  to  contain  a  large 
quantity  of  reducing  sugar  (glucose).  If,  however,  it  be  removed 
immediately  the  animal  is  dead,  its  vessels  washed  out  with  ice-cold 
saline  fluid,  and  be  tlien  cut  up  and  thrown  into  boihng  water,  ground 
and  extracted,  the  extract,  after  separation  of  the  coagulable  proteins, 
contains  hardly  a  trace  of  sugar,  and  no  more  than  is  present  in  the 
blood.  The  fluid  is,  however,  opalescent ;  and  Bernard  fomid  that 
this  opalescence  was  due  to  the  presence  of  a  substance  at  that  time 
new  to  science,  belonging  to  the  class  of  polysaccharides.  The  sub- 
stance he  called  glycogen,  i.e.  the  sugar-former. 

After  a  carbohydrate  meal,  glycogen  may  be  present  in  very  large 
amounts  in  the  liver,  up  to  12  per  cent,  of  the  weight  of  the  fresh  liver. 

899 


900  PHYSIOLOGY 

From  its  solution  in  water  it  can  be  thrown  down  by  the  addition  of 
alcohol  to  GO^per  cent.  When  collected  and  dried,  it  forms  a  snow- 
white  powder,  tasteless  and  odourless,  with  a  formula  identical  with 
that  of  starch,  viz.  CgHioOg.  Like  starch,  it  is  hydrolysed  by  the 
action  of  acids  and  suj)erheated  water,  or  of  amylolytic  ferments,  into 
dextrines,  maltose,  and  finally  glucose.  It  gives  with  iodine  a 
mahogany-red  colour,  which  disappears  on  boiling,  but  returns  again 
on  coohng. 

It  is  not  possible  to  extract  the  whole  of  the  glycogen  from  a  tissue  by  merely 
boiling  it  wdth  water.  Kiilz  introduced  on  this  account  the  method  of  dis- 
solving the  tissues  in  caustic  alkali,  then  tlu-owing  dowii  the  protein  with 
phosj)hotmigstic  acid,  and  in  the  filtrate  precipitating  the  glycogen  with  alcohol. 
This  method  has  been  modified  by  Pfliiger  as  follows  :  100  grm.  of  the  tissue 
(liver  or  muscle)  are  heated  with  100  c.c.  caustic  potash  containing  60  to  70  per 
cent.  KHO  for  twenty-four  hours  in  the  water  bath.  The  solution  is  then 
cooled,  diluted  with  200  c.c.  of  water,  and  treated  with  800  c.c.  alcohol  of 
96  per  cent.  The  precipitate  of  glycogen  is  filtered  off  and  washed  several 
times  with  66  per  cent,  alcohol.  The  precipitate  of  glycogen  is  now  washed 
with  a  little  water  into  a  small  beaker,  neiitralised  carefully  with  acetic  acid, 
and  then  introduced  into  a  100  c.c.  flask.  To  the  solution  5  c.c.  of  hydro- 
chloric acid  of  1-19  sp.  gr.  are  added,  and  the  mixture  is  made  up  to  85  c.c.  The 
flask  is  then  heated  in  the  water  bath  for  three  hom-s.  By  this  means  the 
whole  of  the  glycogen  is  converted  into  glucose,  which  can  be  estimated  by 
Fehling's  method  or  by  Alhhn's  method.  In  practice  it  is  more  accurate 
to  estimate  the  glycogen  in  the  form  of  sugar  than  to  weigh  it  directly.  If 
large  quantities  of  glycogen  are  expected  in  the  tissue,  the  inversion  of  the 
glycogen  must  be  carried  out  in  a  larger  beaker,  and  only  an  aliquot  portion 
taken  for  titration. 

The  large  amount  of  sugar  found  in  the  liver  which  has  been  left 
in  the  body  is  due  to  the  conversion  of  glycogen  into  glucose.  This 
conversion  has  been  variously  ascribed  to  the  activity  of  the  surviving 
liver-cells,  or  to  the  action  of  an  amylase  ferment  present  in  the 
liver-cells.  That  it  is  really  a  ferment  action  is  proved  by  the  fact 
that  the  liver  may  be  dehydrated  with  alcohol,  dried  and  powdered, 
and  kept  for  months  in  this  condition  without  any  alteration  occurring 
in  the  glycogen.  If,  however,  the  coagulated  Hver  be  mixed  with 
water  and  allowed  to  remain  at  the  temperature  of  the  body  for  some 
hours,  the  glycogen  is  found  to  disappear  and  give  place  to  glucose. 

FORMATION  OF  GLYCOGEN 
Glycogen  is  most  readily  formed  from  the  carbohydrates  of  the 
food.  In  order  to  obtain  a  large  amount  from  the  liver,  the  animal 
is  fed  twelve  to  twenty-four  hours  previously  on  a  meal  which  is  rich 
in  carbohydrates.  Not  all  carbohydrates  will  give  rise  to  the  formation 
of  glycogen.  Only  those  which  we  have  mentioned  as  directly 
assimilable,  i.e.  which  will  give  rise  in  the  alimentary  tract  to  mannose, 
glucose,  fructose,  or  galactose,  will   cause   an  increased  formation  of 


THE  METABOLISM  OF  C^VRBOHYDRATES  901 

glycogen.  Tlie  conversion  involves  a  direct  polymerisation  of  the 
glucose,  produced  cither  directly  from  the  foods  or  by  a  molecular 
rearrangement  taking  place  in  one  of  the  other  three  of  these  mono- 
saccharides. 

Glycogen  can  also  be  formed  from  the  proteins  of  the  food,  or 
from  the  products  of  their  disintegration,  the  amino-acid?.  By 
means  which  we  shall  consider  shortly,  it  is  possible  to  free  the 
liver  of  animals  entirely  from  glycogen  :  if  such  animals  be  fed  on  a 
diet  of  washed  fibrin  or  of  pure  caseinogen,  or  even  on  the  ultimate 
products  of  pancreatic  digestion  of  proteins  (containing  therefore  only 
amino-acids),  and  be  killed  shortly  afterwards,  the  liver  is  found  to 
contain  glycogen.  It  does  not  seem  to  be  possible  for  the  liver  to 
manufacture  glycogen  out  of  fats.  At  any  rate,  that  is  the  interpreta- 
tion which  is  generally  placed  on  experiments  on  feeding  with  fats. 
In  these  experiments  it  is  found  that  if  fats  be  administered  to 
an  animal  after  the  liver  has  been  freed  from  glycogen,  although 
the  liver  may  store  up  fats  it  does  not  store  up  any  glycogen. 
The  most  important  source  of  the  glycogen  of  the  liver  is  the 
carbohydrates  of  the  food.  Indeed,  during  a  meal  rich  in  starches 
or  sugars  the  blood  of  the  portal  vein  has  been  found  to  contain  a  much 
larger  proportion  of  sugar  than  the  blood  of  the  hepatic  vein,  or  of  the 
rest  of  the  body. 

If  an  animal  be  starved,  the  glycogen  gradually  disappears  from 
the  liver,  although  even  at  the  end  of  ten  or  twelve  days'  complete 
deprivation  of  food  small  traces  of  glycogen  may  still  be  found  in  this 
organ.  If,  however,  starvation  be  combined  with  hard  work  ;  if,  for 
instance,  a  dog  be  made  to  drag  about  a  milk-cart  on  the  second  day 
of  the  starvation  period,  its  liver  becomes  cj[uite  free  from  glycogen. 
The  same  disappearance  of  glycogen  may  be  produced  by  any  means 
which  evoke  an  increased  muscular  activity,  e.g.  poisoning  with 
strychnine.  Of  the  various  reserve  materials  which  are  available 
the  carbohydrate  is  the  first  to  be  called  upon  to  meet  the  increased 
needs  of  the  tissues  during  functional  activity,  such  as  muscular  work 
or  increased  heat  production.  Thus  the  glycogen  rapidly  disappears 
from  the  liver  of  a  rabbit  which  has  been  immersed  in  a  cold  bath. 

The  glycogen  of  the  liver  represents  a  reserve  material  analogous 
to  the  reserve  carbohydrates  stored  up  as  starch  in  different  parts  of 
plants.  When  the  blood  is  loaded  with  carbohydrates,  a  considerable 
proportion  is  laid  down  as  the  inert  polysaccharide  glvcogen.  As  soon 
as  the  supply  of  sugar  to  the  blood  is  withdrawn,  the  tissues  contiime 
to  use  the  sugar  of  the  blood,  which  is  made  up  at  the  expense  of  the 
glycogen  in  the  liver.  In  every  livcr-oell  tiKMvforea  twofold  proee.ss  ia 
always  going  on,  namely,  a  building  up  of  glycogen  by  the  activity  of 
the  liver-cells,and  a  breaking  down  of  glycogen  under  the  action  of  the 


902 


PHYSIOLOGY 


ferment  formed  in  the  liver-cells.  Which  of  these  two  processes  pre- 
ponderates depends,  in  the  normal  animal,  on  the  percentage  amount 
of  sugar  in  the  blood  which  is  circulating  through  the  organ. 

On  account  of  the  importance  of  glycogen  as  a  reserve  material  it 
is  produced  and  stored  up  in  almost  all  growing  tissues,  to  be  utilised 
in  their  subsequent  development.  Thus  it  is  found  in  large  quantities 
in  the  placenta  during  a  certain  period,  in  foetal  muscles,  and  in  variors 
other  situations.  It  is  found  in  yeast,  in  oysters,  and  in  the  muscles 
of  the  body  generally.  In  foetal  muscles  it  may  amount  to  as  much 
as  40  per  cent,  of  the  total  dried  sohds.  The  glycogen  of  the 
adult  muscle  is  apparently  utilised  during  muscular  work,  and 
diminishes  in  amount  with  activity  of  the  muscle.  In  adult  muscles 
it  never  reaches  anything  hke  the  percentage  which  is  found  in  the  liver. 
The  average  amounts  found  by  Schondorf  in  the  different  tissues  were 
as  follows  : 


Maximum  per  cent, 
of  fresh  tissue 

Minimum  i>cr  cent, 
of  fresh  tissue 

Liver 
Muscle   . 
Heart     . 
Bone 

Intestines 
Skin        . 
Blood     . 

18-69 
3-72 
1-32 
1-90 
1-84 
1-68 
0-0066 

7-300 
0-720 
0-104 
0-197 
0-026 
0-090 
00016 

THE  UTILISATION  OF  SUGAR  IN  THE  BODY 

Arterial  blood  is  always  found  to  contain  between  0*12  and  0"15  per 
cent,  of  sugar  in  the  form  of  glucose.  The  same  amount  is  found 
whether  the  blood  be  taken  from  an  animal  after  a  heavy  carbo- 
hydrate meal  or  from  one  in  a  condition  of  complete  starvation.  The 
constancy  of  the  sugar  content  of  the  blood  suggests  that  this  substance 
is  a  necessary  constituent  of  the  circulating  fluid,  necessary,  that  is 
to  say,  for  the  nutrition  of  the  tissues.  That  it  is  being  used  up  in  all 
the  processes  of  the  body  is  shown  by  the  immediate  alteration  in  the 
respiratory  quotient  which  occurs  when  the  food  is  changed  from  a 
mixed  diet  to  one  consisting  mainly  of  carbohydrate.  An  important 
factor  in  the  maintenance  of  a  constant  sugar  content  in  the  blood  is 
the  reconversion  of  the  stored-up  glycogen  of  the  liver  into  sugar. 
The  glycogen  is  not,  however,  the  sole  source  of  the  sugar,  since  in 
complete  starvation  the  sugar  content  of  the  blood  remains  constant 
even  after  the  last  traces  of  glycogen  have  disappeared  from  the  liver. 
If  the  Uver  be  cut  out  of  the  body  or  removed  from  the  circulation, 
during  the  few  hours  that  the  animal  survives  there  is  a  steady  diminu- 


THE  METABOLISM  OF  CARBOHYDRATES  903 

tion  in  the  blood-sugar,  pointing  to  the  liver  being  the  chief,  if  not  the 
sole,  source  of  the  blood-sugar.  In  some  animals,  e.rj.  the  carnivora,  it 
would  seem  that  the  liver  can  continue  to  supply  sugar  to  the  blood 
on  a  diet  which  includes  only  proteins  and  fats,  and  we  have  already 
seen  that  in  such  animals  glycogen  itself  can  be  stored  up  at  the 
expense  of  protein.  It  is  doubtful  whether  a  perfectly  normal  exist- 
ence is  possible  in  man  in  the  total  absence  of  carbohydrates  from  the 
food,  though  there  is  no  doubt  that  in  the  northern  nations,  e.g.  the 
Eskimos,  the  amount  of  carbohydrate  consumed  is  very  small  in 
comparison  with  the  fats  and  proteins.  During  muscular  exercise  the 
increased  output  of  energy  is  associated  with  a  corresponding 
increase  in  the  absorption  of  oxygen  and  in  the  output  of  carbon 
dioxide,  pointing  to  a  consumption  of  carbohydrate  and  fat  in  the 
contracting  muscles.  We  might  therefore  assume  that  sugar  is  being 
normally  released  by  the  liver  into  the  blood  stream  so  as  to  maintain 
the  proportion  of  this  substance  in  the  blood  at  a  certain  level,  and  that 
the  sugar  is  as  constantly  being  taken  up  and  oxidised  in  the  muscles, 
where  it  serves  as  a  source  of  energy.  According  to  Chauveau  and 
Kaufmann  the  venous  blood  flowing  from  a  contracting  muscle  contains 
less  sugar  than  the  arterial  blood  flo^ving  to  the  muscle.  A  similar 
consumption  of  glucose  has  been  described  as  occurring  in  the  isolated 
contracting  mammalian  heart  when  fed  with  Ringer's  fluid  containing 
a  small  trace  of  glucose.  It  has  long  been  maintained  by  Pavy  that 
the  sugar  which  exists  free  in  the  blood  is  unavailable  for  the  nutrition 
of  the  tissues  and  that  it  must  undergo  some  further  process  of  assimi- 
lation or  synthesis  before  it  can  become  available  as  a  source  of  energy 
to  the  tissues  or  serve  for  the  building  up  of  protoplasm.  It  has  been 
lately  shown  by  Professor  Knowlton,  working  with  the  author,  that 
a  heart,  fed  with  blood  and  performing  a  normal  amount  of  work,  is 
able  to  use  up  sugar,  the  consumption  of  sugar  amounting  to  about 
4  mg.  per  gramme  of  heart  muscle  per  hour.  That  the  question  of 
utilisation  of  sugar  by  the  tissues  is  highly  complex  is  shown  by  a 
study  of  the  conditions  under  which  sugar  may  appear  in  the  urine. 
We  learn  thereby  to  appreciate  to  some  extent  the  significance  of 
carbohydrates  both  as  sources  of  energy  and  as  foods  for  the  tissues, 
though  we  are  still  a  long  way  from  unravelling  all  the  changes  which 
the  sugar  must  undergo  in  the  cell  before  it  appears  once  again  in  the 
oxidised  products,  carbon  dioxide  and  water. 

GLYCOSURIA 

Normal  urine  always  contains  a  small  proportion  of  sugar,  about 

1  part  per  1000,  i.e.  in  about  the  same  proportion  as  the  blood  itself. 

For  the  detection  of  these  small  traces  of  sugar  in  the  urine  special 

methods  are  necessary.     The  term  glycosuria  is  not  employed  unless 


904  PHYSIOLOGY 

sugar  appears  in  quantities  large  enough  to  give  a  reaction  with 
Fehhng's  sohition  or  with  the  phenylhydrazine  test.  Such  a  condition 
may  easily  be  brought  about  by  the  injection  of  sugar  subcutaneously  or 
intravenously.  It  is  then  found  that  any  trace  of  the  disaccharides, 
cane  sugar  or  lactose,  introduced  in  the  circulation,  is  excreted  in  the 
nrine.  A  rather  larger  quantity  of  maltose  may  be  injected  slowly 
without  appearing  in  the  urine,  since  the  blood-serum  contains  a 
ferment  maltase,  which  converts  the  maltose  into  glucose.  Glucose, 
fructose,  mannose,  or  galactose,  if  introduced  slowly  into  the  circula- 
tion, are  stored  up  as  glycogen  in  the  liver.  If,  however,  the  per- 
centage of  sugar  in  the  blood  rises  above  2  parts  per  1000,  the  sugar 
(generally  glucose)  appears  in  the  urine.  When  this  condition  of 
hyperglyc8Bmia  (excess  of  sugar  in  the  blood)  is  set  up,  the  constitution 
of  the  sugar  in  the  urine  no  longer  corresponds  to  that  in  the  blood. 
If  the  blood  contains,  e.g.  4  parts  per  1000,  the  urine  may  contain  from 
2  to  7  per  cent,  of  sugar.  Up  to  a  certain  point,  then,  blood-sugar  is 
kept  back  by  the  kidneys  as  a  necessary  food  material  for  the  tissues. 
Any  excess  above  the  normal  apparently  acts  as  a  foreign  substance 
and  is  excreted  by  the  kidneys  in  a  concentration  much  greater  than 
that  in  which  it  exists  in  the  blood-serum. 

(1)  ALIMENTARY  GLYCOSURIA.  A  state  of  hyperglycEemia 
may  be  induced  by  the  administration  of  abnormally  large  quantities 
of  glucose  by  the  alimentary  canal.  The  amount  has  to  exceed 
in  a  healthy  individual  100  grm.  in  order  that  it  shall  appear  in  the 
urine.  In  certain  individuals  the  power  of  assimilating  glucose 
may  be  deficient  so  that  an  ahmentary  glycosuria  may  be  caused  by 
any  over-indulgence  in  carbohydrate  food.  In  the  healthy  person  it 
is  hardly  possible  to  produce  glycosuria  by  the  administration  of 
starchy  foods,  since  the  liver  can  store  up  the  excess  of  glucose  as  fast 
as  it  is  produced  from  the  starch  by  digestion  and  absorbed  into  the 
blood-serum. 

(2)  DIABETIC  PUNCTURE.  It  was  shown  by  Claude  Bernard 
that  puncture  of  the  floor  of  the  fourth  ventricle  in  rabbits  was  often 
followed  immediately  by  an  excessive  secretion  of  urine  and  the 
appearance  of  sugar  in  this  fluid.  The  glycosuria  may  last  from 
twenty-four  to  thirty  hours.  If  at  the  end  of  this  time  the  animal 
be  killed,  the  liver  is  found  to  be  free  from  glycogen.  A  sample  of 
blood  taken  during  the  height  of  glycosuria  may  contain  from  3  to 
4  parts  of  sugar  per  1000.  In  order  that  the  experiment  may  succeed 
it  is  important  that  the  animal  be  previously  well  fed.  If  the  puncture 
or  '  piqiire  '  be  carried  out  on  an  animal  that  has  been  starved  or 
whose  liver  has  been  freed  by  any  means  from  glycogen,  no  glycosuria 
is  produced.  It  is  evident  that  the  effect  of  the  puncture  has  been  to 
cause  a  rapid  conversion  of  the  glycogen  previously  stored  up  in  the 


THE  MRTAB0LI8M  OF  rARBOHYDRATES     9C'5 

liver  into  glucose.  The  glucose  so  formed  escapes  into  the  blood, 
raising  the  sugar  content  of  this  fluid  above  the  normal,  and  the 
excess  is  immediately  excreted  by  the  kidneys  together  with  an 
increased  amount  of  water.  The  exact  manner  in  which  the  liver  is 
affected  by  the  puncture  cannot  be  regarded  as  definitely  ascertained. 
It  has  been  variously  explained  as  due  to  vasomotor  changes  in  the 
liver  and  the  flooding  of  this  organ  with  arterial  blood,  or  to  the  direct 
stimulation  or  paralysis  of  trophic  or  secretory  fibres  passing  from  the 
medulla  to  the  liver  by  way  of  the  vagus  nerves.  It  is  possible  that 
the  occurrence  of  sugar  in  the  urine  which  may  occur  after  head 
injuries  is  brought  about  in  a  similar  way.  The  glycosuria  after 
operations,  administration  of  anaesthetics,  &c.,  is  probably  due  to  a 
similar  disturbance  of  the  glycogen-retaining  function  of  the  Uver. 

(3)  PHLORIDZIN  DIABETES.  Phloridzin  is  a  glucoside  extracted 
from  the  root  cortex  of  the  apple-tree.  It  may  be  decomposed  into 
a  sugar  and  phloretin.  Wlien  phloridzin  or  phloretin  is  administered 
by  the  mouth  or  subcutaneously  it  gives  rise  to  glycosuria,  unaccom- 
panied, at  first  at  any  rate,  by  any  other  s\Tnptom.  The  urine  may 
contain  from  5  to  15  per  cent,  of  glucose.  The  glycosuria  induced  in 
this  way  differs  from  the  forms  already  described  in  the  fact  that  it  is 
not  due  to  hyperglycaemia.  Analysis  of  the  blood  shows  that  the  sugar 
is  slightly  diminished  rather  than  increased.  The  excretion  of  glucose 
seems  to  be  due  to  a  specific  effect  of  the  drug  upon  the  kidneys.  If 
a  cannula  be  placed  in  the  two  ureters  so  as  to  collect  the  urine  from 
each  kidney  separately  and  a  small  dose  of  phloridzin  be  then  injected 
by  a  hypodermic  syringe  into  the  left  renal  artery,  the  urine  flowing 
from  the  left  ureter  in  two  minutes  will  be  found  to  contain  sugar, 
while  the  urine  from  the  right  kidney  ^^■ill  not  contain  any  sugar  for 
another  five  or  ten  minutes.  The  effect  therefore  is  to  rapidly  drain 
off  sugar  from  the  blood.  In  order  to  maintain  the  sugar  content  of 
the  blood  at  its  normal  height  the  liver  must  rapidly  manufacture 
fresh  sugar  to  take  the  place  of  that  lost  by  the  kidneys.  In  the  first 
instance  the  liver  will  utilise  its  stored-up  glycogen  for  this  purpose. 
If  a  dose  of  phloridzin  be  given  to  each  of  two  animals  and  one  animal 
killed  as  soon  as  the  excretion  of  sugar  is  coming  to  an  end.  the  Hver 
will  be  found  free  from  glycogen.  If  now  a  second  dose  of  phloridzin 
be  given  to  the  other,  which  may  be  regarded  as  glycogen-free, 
glycosuria  is  produced  as  before,  and  the  excretion  of  sugar  can  be 
continued  indefinitely  by  repeated  administration  of  the  drug.  So 
long  as  sufficient  food  is  given,  including  carbohydrates,  the  loss  of 
sugar  does  not  entail  any  increase  in  the  destruction  of  the  tissues  ; 
but  if  the  drug  be  administered  to  starving  animals  the  waste  of  sugar 
has  to  be  made  good  at  tiie  expense  of  material  otluT  than  carbo- 
hydrate.    The  source  of  the  sugar  excreted  under  these  circumstances 


906 


PHYSIOLOGY 


is  the  protein  of  the  tissues.  The  nitrogen  excreted  in  the  urine  rises 
in  amount  in  proportion  to  the  quantity  of  sugar  excreted,  and  there 
is  a  constant  ratio  between  the  amount  of  nitrogen  and  the  amount 
of  sugar  excreted  in  the  urine.  In  some  experiments  this  ratio  D  :  N 
has  been  2-8  :  1.  If  meat  be  administered  to  such  starving  animals 
with  glycosuria,  the  D  :  N  ration  does  not  alter  ;  the  amount  of 
nitrogen  in  the  urine  increases,  but  the  sugar  increases  in  the  same 
proportion.  The  sugar  production  is  therefore  proportional  to  the 
protein  metabohsm  and  must  be  derived  from  protein.  The  source 
of  the  sugar  is  the  amino-acids  of  which  the  protein  is  composed.  In 
one  experiment  in  which  pancreatic  digest  of  meat  was  given  to  a 
phloridzinised  dog,  24  grm.  of  glucose  were  excreted  for  each 
gramme  of  nitrogen.  In  the  same  way,  glycine,  alanine,  and  asparagine 
increase  the  glucose  output  in  such  an  animal.  We  must  assume  that 
the  amino-acids  produced  in  digestion  or  by  the  autolysis  of  the 
tissues  undergo  deamination  and  that  the  sugar  is  formed  by  a  process 
of  synthesis  from  the  oxyacids  thereby  produced.  On  the  other  hand, 
the  administration  of  fat  to  phloridzinised  dogs  gives  no  increase  in 
the  output  of  sugar.  The  drain  of  sugar  from  the  organism  determined 
by  the  action  of  phloridzin  on  the  kidneys  thus  necessitates  a  continued 
breakdown  of  the  nitrogenous  tissues  of  the  body  in  the  efiort  to 
maintain  a  normal  supply  of  sugar  to  the  tissues,  and  unless  excessive 
feeding  be  employed  the  animal  must  waste.  The  great  increase  in 
the  nitrogenous  output  resulting  from  the  condition  of  phloridzin 
diabetes  is  shown  in  the  following  Table  (Lusk)  : 


GOAT 

Dog 

I» 

N                 D :  N 

D 

N 

D:N 

Fasting     . 

Fasting     . 

Fasting  and  dia- 
betic 

Fasting  and  dia- 
betic 

Fasting  and  dia- 
betic 

Fasting  and  dia- 
betic     . 

20-33 
26-08 
23-39 
19-01 

3-72 
3-71 

4-90 

8-83 
8-06 
6-84 

415 

2-9.5 
2-90 

2-78 

63-55 
65-30 
65-84 
64-60 

4-04 
4-17 

12-66 

18-76 

18-57 

17-29 

502* 
3-38 
3-54 
3-74 

The  constant  drain  of  sugar  will  in  time  involve  a  relative  carbo- 
hydrate starvation  of  the  tissues,  which  will  make  good  their  energy 

*  The  high  D  :  N  ratio  on  the  first  day  is  evidently  due  to  the  conversion 
of  the  glycogen  still  present  in  the  body. 


THE  METABOLISM  OF  CARBOHYDRATES  907 

requirements  as  much  as  possible  at  the  expense  of  protein  and  fat. 
The  administration  of  meat  will  diminish  the  fat  metabolism  to  a 
certain  extent,  but  since  it  does  not  alter  the  D  :  N  ratio  it  would  appear 
that  the  latter  does  not  depend  in  any  way  on  the  quantity  of  fat 
undergoing  oxidation.  This  is  shown  in  the  following  respiration 
experiment  (Mandel  and  Lusk)  on  a  dog  with  phloridzin  glycosuria,  in 
which  the  metabolism  during  starvation  and  after  ingestion  of  meat 
was  determined  : 


_.  .  -T                Calories  from 
protein 

1 

Calories  from 
fat 

Calories 
total 

F'a^tiiig 

:5ii(i  crrm.  meat 

3-69 
3-55 

80-2 
161-9 

274-4 
261-7 

354-6 
423-6 

The  enormous  waste  of  energy  involved  in  such  a  constant  loss  of 
sugar  will  be  apparent  if  we  consider  that  a  D  :  N  ration  of  3-65  means 
that  52-5  per  cent,  of  the  energy  in  the  protein  taken  as  food  or  set 
free  from  the  tissues  is  lost  to  the  organism  in  the  form  of  glucose. 
According  to  Rubner  28-5  of  the  energy  of  meat  protein  is  not  utilised 
in  the  body,  but  is  liberated  simply  as  heat.  This  stimulating  effect 
of  protein  on  metabolism  or  on  the  processes  of  oxidation  in  the  body 
is  described  by  Rubner  as  the  '  specific  d\Tiamic  action  '  of  proteins. 
If  we  accept  this  view  and  add  this  28-5  per  cent,  lost  as  heat  to  the 
52-5  per  cent,  lost  as  sugar  there  would  remain  a  balance  of  only 
19  per  cent,  actually  available  for  the  vital  activities  of  the  tissues.  It 
is  not  to  be  wondered  at  that  the  nitrogenous  metabolism  may  be 
increased  three  to  five  fold  as  a  result  of  the  artificial  induction  of 
the  diabetic  condition. 

The  carbohydrate  starvation  has  other  deleterious  effects,  since 
we  have  evidence  that  a  certain  amount  of  carbohydrate  food  is  a 
necessary  condition  for  both  fat  and  protein  metabolism.  The 
necessity  of  carbohydrate  for  the  assimilation  of  protein  is  brought 
out  in  an  experiment  by  Oathcart.  It  has  long  been  known 
that  carbohydrate  administration  has  a  sparing  effect  on  protein 
metabolism.  If  an  animal  or  man  be  starved,  the  nitrogenous  output 
sinks  to  a  certain  level  and  there  remains  practically  stationary.  If 
now  pure  carbohydrate  food  be  administered  sufficent  to  meet  the 
energy  requirements  of  the  animal  or  man  (about  35  calories  per  kilo), 
there  is  at  once  a  rapid  drop  in  the  output  of  nitrogen  and  therefore 
in  the  protein  waste  of  the  tissues.  Fat  has  a  much  slighter  or  no 
sparing  effect  on  the  nitrogenous  metabolism.  Indeed  in  certain 
experiments  by  Cathcart  the  administration  of  fat  caused  an  actual 
rise  in  the  nitrogenous  output.     The  same  contrast  between  carbo- 


908 


PHYSIOLOGY 


hydrate  and  fat  is  shown  in  their  influence  on  the  excretion  of  creatine. 
This  substance  is  not  present  in  normal  urine,  but  ahnost  invariably 
makes  its  appearance  during  starvation.  If  carbohydrates  be  adminis- 
tered after  a  period  of  starvation  the  creatine  disappears  from  the 
urine.  On  a  pure  diet  of  fat;  however,  as  much  creatine  is  found  in 
the  urine  as  during  complete  starvation.  These  facts  are  well  brought 
out  in  the  following  Tables.  Table  I  shows  the  effect  of  the  administra- 
tion of  pure  carbohydrate  after  a  forty  hours'  fast.  Table  II  shows 
the  effect  of  fat  and  of  fat  plus  protein  after  a  fast.  In  Table  III  the 
fast  was  only  relative,  the  diet  during  the  first  five  days  consisting 
almost  entirely  of  carbohydrates,  during  the  next  two  days  of  almost 
pure  fat  (cream),  and  on  the  last  day  an  ordinary  mixed  diet. 


TA 

BLE 

I 

Day 

XlTROGEN 

IN    GRM. 

Per  Cent,  of  Total  Kitrogen 

of 

.3 

r- 

5 

s 

— 

Diet 

Exp. 

5 

Zj 

= 

c 

= 

'~ 

= 

= 

03 

<A 

"S 

;; 

£ 

tH 

2 

r, 

i-i 

£ 

'Z 

.- 

.^ 

^ 

^ 

" 

P 

o 

o 

P 

* 

-' 

^ 

^ 

1 

6-80 

0-33 

•423 

•076 

•433 

•057 

78^3 

6-2 

11 

6-3 

0-9 

Fast 
(+H2O) 

2 

6-85 

5-61 

•521 

•080 

•438 

•007 

81-9 

7-C) 

13 

6-4 

0^1 

Carbo- 
hydrate 

3 

714 

— ■ 

— 

— 

•535 

■005 

— 

— 

— 

7-4 

0-1 

Mixed 

Carbohydrate  diet : 


Tapioca      =   454  grm. 
Sugar  =114      „ 

Honey        =227      „ 
Cornflour  =     85      „ 

Calorie  intake  =  40  cal.  per  kilo 


Carbohydrate  in  Faeces 
19^0  grm. 
4^5      „ 


Cathcart  concludes  from  these  observations  that  the  presence  of 
carbohydrates  is  essential  for  the  utilisation  of  the  protein  given  in  the 
diet.  This  conclusion  is  borne  out  by  the  results  of  feeding  animals 
with  proteins  which  have  been  digested  with  pancreatic  juice  until 
the  biuret  reaction  has  disappeared.  After  Loewi  had  shown  that 
it  was  possible  to  maintain  nitrogenous  equilibrium  in  dogs  with  such 
a  digest.  Lesser  was  unable  to  confirm  his  results  ;  but  it  has  been 
pointed  out  that  the  essential  difference  between  the  two  observers 
was  that  Loewi  gave  an  abundant  supply  of  carbohydrates  with  the 
digest,  while  Lesser  omitted  carbohydrates  altogether  and  administered 
fats  and  protein  digest  alone. 

The  evidence  that  the  carbohydrates  play  a  necessary  part  in  the 
metabolic  history  of  fats  has  already  been  mentioned,  (v.  p.  895).      We 


THE  METABOLISM  OF  CARBOHYDRATES 

lAIJl.K  11 


909 


Day 

of 

Exp. 

NlTKOGEN   IN   GRM. 

Per  Cent,  of  Total  Nitrogen 

Dirt 

I 

^ 

o 

a 

P 

2 

1 

o 

O 

1 

7()2 

6-33 

•396 

•082 

•424 

•051 

83^2 

5^2 

110 

5^5 

0-7 

Fast 
(+H2O) 

2 

11  07 

8-54 

•564 

•043 

•370 

•141 

731 

4^8 

0^36 

31 

1-2 

Fat 

3 

o-oy 

7-43 

•945 

•038 

•353 

•122 

Sl-1 

10-3 

042 

3^8 

14 

„ 

4 

lo-44 

12-41 

1  -000 

•128 

•372 

•118 

80^3 

10^3 

0^82 

24 

0^7 

Fat    pro- 
tein 
(sugar 
free) 

5 

17  04 

13-04 

b520 

•193 

•420 

•130 

76^5 

8^8 

MO 

24 

0-8 

>» 

6 

14-28 

•497 

•085 

3-4 

0-7 

Mixed, 
little 
carbo- 
hj^drate 

8 

— 

— 

— 

— 

•534 

•000 

— 

— 

— 

— 

0^0 

Mixed, 

ordinary 

Fat  diet.     570  grm.  cream  (55  per  cent,  fat)  =  312  grm.  fat. 

Faeces  =18   grm.   fat.     (The   fat   on   the   whole   Avas    well 
very  slight  diarrhoea  caused.) 

Fat  protein  diet : 

Casein  bread  (carbohydrate  free)  = 
Cheese     .         .         .  .  .   = 

Butter     .         .  .  .  .   = 


40  cal.  per  kilo, 
utilised.     Only 


170  grm. 

43      „ 
128      „ 

12      ., 


39  cal.  per  kilo. 
TABLE  III 


Day 

t.f 

Kxp. 

NiXKO(Ji;> 

■  in  Ou.m. 

Per  Cest. 

3F  Total  >Mtkouen 

Diet 

0 
£ 

3 
5 

0 
a 

Zj 

0 

Is 

0 

c3 
t-, 

c 
0 

'3 

0 

a 
a 

0 

0 
a 

g 

0 

1 

6^79 

4-61 

•375 

•123 

•478 

•004 

67^8 

5-5 

1-8 

7-04 

•06 

Carbo- 
hydrate 

2 

640 

465 

•134 

•173 

•460 

•015 

72-7 

2-1 

27 

7^18 

•24 

., 

3 

4-77 

3-21 

•132 

•146 

•413 

•007 

67-2 

2-7 

31 

8^65 

•15 

>' 

4 

4-79 

317 

•121 

•152 

•450 

•004 

66-2 

2-5 

31 

937 

•08 

,, 

5 

439 

3-31 

•104 

•125 

•436 

•000 

75-3 

2-3 

2^8 

9-93 

•00 

„ 

() 

4-83 

376 

•238 

•157 

•400 

•019 

77-8 

4^9 

32 

8-28 

•39 

Fat 

7 

8-13 

6-64 

•527 

•088 

•347 

•091 

81^6 

6-4 

11 

4-26 

112 

„ 

8 

16-21 

13-45 

1130 

•551 

•477 

•001 

83-0 

6-9 

3-4 

2-94 

0-00 

Mixed 

910  PHYSIOLOGY 

have  seen  that  in  the  absence  of  carbohydrates  the  last  stages  in  the 
oxidation  of  fats  make  default  so  that  the  partially  oxidised  fatty 
acids,  oxybutyric  acid  and  aceto-acetic  acid,  accumulate  in  large 
quantities  and  are  excreted  as  such  or  as  acetone  in  the  urine.  Not 
only  does  this  involve  a  loss  of  energy  to  the  body,  but  these  organic 
acids  require  other  bases  for  their  neutrahsation.  Up  to  a  certain 
point  they  will  be  excreted  in  the  urine  in  combination  with  the  fixed 
alkalies.  When  these  are  no  longer  present  in  sufficient  quantity  they 
will  be  excreted  in  combination  with  ammonia,  so  that  the  ammonia 
of  the  urine  is  largely  increased  {v.  Table  III).  If  the  condition  of 
carbohydrate  starvation  be  continued,  this  mechanism  of  neutralisa- 
tion is  insufficient  and  the  phenomena  of  acidosis,  dyspnoea  and  coma, 
ensue,  resulting  in  the  death  of  the  animal. 

Another  effect  of  continued  administration  of  phloridzin  is  fat 
infiltration  of  the  liver.  This  is  merely  a  result  of  the  carbohydrate 
starvation.  A  similar  condition  of  fat  infiltration  can  be  brought 
about  by  feeding  with  a  pure  protein  plus  fat  diet.  The  liver  seems  to 
be  able  to  act  as  a  storehouse  either  of  fat  or  of  carbohydrate,  so  that 
there  is  an  inverse  ratio  between  the  amount  of  glycogen  and  the 
amount  of  fat  stored  up  in  the  liver  at  any  given  time.  It  has  been 
shown  that  the  fat  in  the  liver  under  these  circumstances  is  simply 
fat  which  has  been  transferred  to  this  organ  from  the  ordinary  fat 
depots,  subcutaneous  tissues,  &c.,  of  the  body. 

(4)  PANCREATIC  DIABETES.  Von  Mering  and  Minkowski  found 
that  total  excision  of  the  pancreas  gives  rise  to  a  severe  and  rapidly 
fatal  diabetes,  which  presents  many  similarities  to  the  severer 
cases  of  diabetes  in  man.  One  of  the  main  difficulties  in  the 
operation  of  excision  of  the  pancreas  lies  in  the  fact  that  the 
tissues  of  a  diabetic  are  extremely  prone  to  infection.  It  is  almost 
impossible  after  total  excision  of  the  pancreas,  when  diabetes  has  been 
set  up,  to  procure  healing  of  the  wounds  without  suppuration.  The 
operation  is  therefore  usually  carried  out  in  two  stages.  In  the  first 
stage  one  small  portion  of  the  tail  of  the  pancreas  is  transplanted 
under  the  skin  of  the  abdomen,  while  the  rest  of  the  gland  is  excised. 
Such  animals  do  not  get  diabetes  and  therefore  have  a  chance  of 
recovery  from  the  severe  operation.  When  the  wounds  are  quite 
healed  the  transplanted  portion  is  removed  through  a  simple  skin 
incision.  The  second  operation  is  followed  in  a  few  hours  by  the 
appearance  of  a  large  amount  of  sugar,  5  to  10  per  cent,  in  the  urine. 
The  glycosuria  persists,  the  animal  rapidly  wastes,  and  finally  dies 
at  the  end  of  two  to  three  weeks  from  diabetic  coma.  From  the 
nature  of  the  operation  it  is  evident  that  the  condition  of  diabetes 
observed  under  these  circumstances  has  nothing  to  do  with  the  presence 
or  absence  of  the  pancreatic  secretion  from  the  intestine,  since  this 


THE  METABOLISM  OF  CARBOHYDRATES  911 

secretion  is  cut  off  at  the  first  operation  and  diabetes  does  not  make  its 
appearance  until  the  second  small  portion  of  the  gland  is  removed. 
Moreover  ligature  of  the  ducts  of  the  pancreas  or  obstruction  of  the 
ducts  by  the  injection  of  melted  paraffin  does  not  give  rise  to  diabetes. 
The  excretion  of  sugar  by  the  kidneys  is  due  to  an  increase  in  the 
sugar  content  of  the  blood.  The  blood-sugar  may  amount  to  between 
4  and  5  parts  per  1000.  This  state  of  hyperglycaBmia  and  the  excretion 
of  sugar  in  the  urine  persist  even  when  the  animal  is  completely  starved 
or  is  fed  on  a  pure  protein  or  protein  flus  fat  diet.  Moreover,  as  in 
phloridzin  glycosuria,  we  find  a  constant  ratio  between  the  sugar  and 
the  urinary  nitrogen,  the  D  :  N  ratio  being  either  2-8  or  3-65.  The 
administration  of  protein  food  to  an  animal  previously  starved  increases 
the  output  of  nitrogen,  but  increases  at  the  same  time  the  output  of 
glucose.  No  similar  increase  in  the  glucose  excretion  is  observed  as  a 
result  of  the  administration  of  fat.  We  must  conclude  therefore  that 
in  the  absence  of  carbohydrate  from  the  diet  the  excess  of  sugar  in 
the  blood  as  well  as  that  escaping  by  the  urine  is  derived  from  the 
breakdown  of  the  proteins  of  the  tissues.  On  the  other  hand,  the 
power  of  the  animal  to  assimilate  or  utiUse  carbohydrate  is  entirely 
abolished.  Glucose  or  dextrose  administered  to  a  starving  animal 
with  pancreatic  diabetes  appears  quantitatively  in  the  urine.  The 
amount  taken  by  the  ahmentary  canal  is  simply  added  to  the  amount 
which  would  have  been  excreted  if  no  food  had  been  given.  Glycogen 
disappears  entirely  from  the  liver ;  and  the  tissues  generally,  though 
bathed  in  a  blood  containing  double  its  normal  content  of  sugar,  are 
unable  to  assimilate  the  sugar  and  to  build  it  into  glycogen,  or  to  take 
it  up  into  the  cells  in  the  form  which  is  the  necessary  condition  for 
its  utilisation.  Though  plentifully  supplied  with  sugar,  thev  suffer 
from  sugar  starvation  and  react  in  the  same  way  as  when  the  sugar 
starvation  is  induced  by  a  diet  consisting  purely  of  fats  or  by  a  drain 
of  sugar  from  the  body  in  consequence  of  abnormal  functioning  of  the 
kidneys.  The  results  are  exactly  analogous  to  those  we  have  studied 
in  the  case  of  phloridzin  diabetes.  There  is  a  rapid  wasting  of  all  the 
tissues  of  the  body,  including  the  fats  and  proteins,  and  finally 
the  animal  is  destroyed  by  the  accmnulation  of  the  products  of 
iiupei-fect  oxidation  of  the  fatty  acids.  The  fiver  apparently  uses 
up  the  proteins,  the  amino-acids,  and  some  of  the  lower  fatty  acids, 
e.g.  acetic,  propionic,  and  lactic,  and  glycerin,  for  the  manufacture  of 
the  sugar  that  the  tissues  lack  ;  but  all  to  no  purpose,  since  these 
tissues  are  unable  to  utilise  any  of  the  sugars  so  formed. 

Why  removal  of  the  pancreas  brings  about  this  disabihty  to 
assimilate  sugar  is  still  a  matter  of  speculation.  It  is  generally 
assumed  that  the  pancreas,  in  addition  to  the  manufacture  of  a  diges- 
tive juice,  produces  an  internal  secretion,  a  honnone,  which  passes 


912  PHYSIOLOGY 

into  the  blood  stream  and  is  carried  to  all  the  tissues  of  the  body  to 
act  as  a  necessary  link  or  amboceptor  in  the  assimilation  of  carbo- 
hydrates. Until  recently  there  was  no  positive  evidence  for  this  view. 
Administration  of  the  pancreas  itself  or  of  extracts  of  the  pancreas, 
either  by  the  mouth  or  subcutaneously,  has  no  definite  efiect  on  the 
course  of  the  disorder.  On  the  other  hand,  an  isolated  heart  from  a 
diabetic  animal,  when  perfused  with  blood  plus  glucose  from  the  same 
animal,  is  unable  to  consume  glucose  ;  but,  on  adding  a  decoction  of 
fresh  pancreas,  a  consumption  of  sugar  is  observed,  which  may  attain 
the  same  degree  as  that  in  a  normal  heart  (Knowlton  and  Starling). 
If  the  pancreatic  cells  do  produce  such  a  hormone,  the  production 
must  be  a  gradual  one,  in  response  to  the  needs  of  the  body,  and  is 
not  attended  by  the  accimiulation  of  sufficient  quantities  of  the 
hormone  in  the  gland  as  to  exert  a  curative  influence  on  the  whole 
animal  when  administered  in  extracts  of  the  gland.  It  has  been 
suggested  that  the  islets  of  Langerhans  are  responsible  for  this 
hypothetical  internal  secretion,  and  changes  in  these  islets  have 
been  described  in  cases  of  diabetes  in  man.  There  is  no  satisfactory 
evidence  for  this  assimiption,  and,  as  we  have  seen  already,  it  seems 
possible  that  the  islets  represent  a  stage  in  the  development  of  the 
ordinary  secreting  tissue  of  the  gland. 

(5)  DIABETES  IN  MAN.  In  its  severer  forms  the  diabetes  of  man 
resembles  very  closely  that  produced  in  the  dog  by  total  extirpation 
of  the  pancreas.  The  output  of  urine  is  largely  increased  and  the 
frequency  of  micturition  is  often  the  first  symptom  noticed.  On 
examination  the  urine,  though  light  in  colour,  is  of  a  high  specific 
gravity,  1030  to  1035,  and  may  contain  from  5  to  10  per  cent,  of  sugar. 
The  appetite  is  largely  increased,  but  in  spite  of  the  large  amount  of 
food  taken  the  body  wastes.  The  excessive  quantity  of  fluid  lost  by 
the  body  gives  rise  to  a  constant  thirst.  The  patient  may  die  after 
some  months  or  years  in  a  condition  of  diabetic  coma.  Warning  of 
the  onset  of  this  condition  is  given  by  the  rise  of  ammonia  in  the  urine 
and  by  the  appearance  of  oxy butyric  and  diacetic  acids.  The 
breath  may  smell  of  acetone,  and  this  substance  may  also'  be  present 
in  the  urine.  On  the  other  hand,  the  diabetic  state  is  attended  by 
diminished  resistance  of  the  tissues  to  infection.  A  pimple  may 
become  a  carbuncle  ;  a  shght  sore  on  the  foot  may  give  rise  to  a 
rapidly  spreading  gangrene  of  the  lower  extremity  ;  tubercular  infec- 
tion of  the  lungs  spreads  rapidly  to  the  whole  organ  so  as  to  simulate 
pneumonia.  The  patient  may  thus  die  of  some  such  intercurrent 
infection  before  the  onset  of  coma.  In  a  few  cases  the  pancreas 
is  found  to  be  atrophied  or  diseased,  but  in  the  large  majority  no 
marked  pathological  change  is  to  be  observed  in  this  organ.  Yet  the 
condition  is  essentially  similar  to  that  which  occurs  in  pancreatic 


THE  METABOLISM  (JF  CARBOHYDRATES  913 

diabetes.  The  radical  defect  is  the  inability,  relative  or  complete,  of 
the  organism  to  assimilate  carbohydrate.  We  may  find  all  grades 
between  such  cases  and  those  in  which  there  is  still  a  considerable 
power  of  assimilation.  In  order  to  determine  the  grade  of  the  dis- 
order it  is  usual  to  give  a  test  diet  with  a  certain  proportion  of  carbo- 
hydrate, e.g.  100  grm.  of  bread  with  meat,  bacon,  eggs,  butter,  green 
vegetables,  cheese,  lettuce,  coffee  and  wane.  If  the  urine  remains  free 
from  sugar  on  this  diet,  the  diabetes  is  mild  in  character.  More  bread 
may  then  be  added  to  the  diet  from  time  to  time  until  sugar  appears 
in  the  urine  and  the  hmit  of  tolerance  for  carbohydrate  has  been 
reached.  In  many  cases  the  sugar  will  disappear  from  the  urine  on 
the  administration  of  a  diet  consisting  entirely  of  proteins  and  fats. 
When  this  has  been  effected  carbohydrates  may  be  added  in  small 
proportions  to  the  diet  until  the  limit  is  found  at  which  the  assimilatory 
powders  of  the  patient  are  reached.  It  seems  that  administration  of 
any  carbohydrate  in  excess  of  this  limit  is  of  disadvantage  to  the 
patient  and  hastens  the  progress  of  his  disorder.  When  the  power  of 
assimilating  carbohydrates  is  entirely  abolished  the  prognosis  is  almost 
absolutely  fatal.  This  point  may  be  determined  in  two  ways.  In 
the  first  place,  a  patient  with  no  powder  of  carbohydrate  assimilation 
will  continue  to  excrete  sugar  in  the  urine  on  a  pure  protein  fat  diet, 
and  the  D  :  N  ratio  will  be  2-8  or  higher.  Information  may  also  be 
obtained  from  a  study  of  his  respiratory  quotient.  The  production 
of  dextrose  from  protein  involves  the  absorption  of  oxygen.  Oxygen 
will  therefore  be  taken  in  which  will  not  reappear  as  carbon  dioxide 
ill  the  expired  air.  In  severe  cases  of  diabetes  therefore  the  respira- 
tory quotient  will  fall  below  that  representing  fat  metabolism,  i.e. 
below  0-7.  In  most  cases  of  diabetes,  where  there  is  still  some  power 
of  assimilating  carbohydrate  and  of  storing  up  glycogen,  the  respiratory 
quotient  will  be  found  approximately  normal.  A  very  low  respiratory 
quotient  is  a  sign  of  the  severity  of  the  disorder. 

This  study  of  the  conditions  of  carbohydrate  metabolism  shows 
how  all  three  classes  of  food-stuffs  co-operate  in  the  maintenance  of  the 
chemical  processes  which  lie  at  the  root  of  the  existence  and  the 
activities  of  living  organisms.  We  see  how  fallacious  were  the  ideas 
that  the  proteins  alone  were  necessary  for  life  and  that  protoplasm 
was  simply  living  protein.  Protoplasm,  i.e.  the  material  substrate  of 
life,  must  be  regarded  as  a  complex  in  which  proteins,  fats,  carbo- 
hydrates, nucleins,  salts,  and  water  all  play  a  part  and  of  which  each 
is  an  essential  constituent.  In  the  higher  animals  proteins  are  neces- 
sary to  furnish  the  proteins  of  the  tissues,  and  the  food  must  contain 
just  those  ainino-acids  which  are  riMpiisite  for  the  building  up  of  the 
proteins  characteristic  of  each  separate  tissue.  Moreover  certain 
groups  of  the  protein  molecule  appear  to  be  destined  to  serve  as 

68 


914  PHYSIOLOGY 

mother-substances  of  hormones  and  other  chemical  compounds  which 
play  a  dynamic  rather  than  static  part  in  the  phenomena  of  hfe,  and 
supply  conditions  of  activity  rather  than  material  for  the  production 
of  energ}\  The  carbohydrates  not  only  act  as  sources  of  energy,  but 
are  necessary  to  the  building  up  of  the  proteins  into  the  protoplasmic 
complex.  Without  them  moreover  this  complex  cannot  properly 
utiUse  the  fat  contained  in  itself  or  supplied  in  its  food.  On  the 
other  hand,  the  carbohydrates  by  themselves  are  not  available  as  food, 
but  require  some  connecting  link,  which  may  be  protein  or  nitrogenous 
in  character,  to  enable  their  association  with  the  active  part  of  the 
protoplasm  and  their  utilisation  by  oxidation.  At  the  same  time 
there  is  a  certain  possibihty  of  interconversion  between  these  difEerent 
substances  ;  sugar  may  be  formed  from  proteins,  fats  from  carbo- 
hydrates. On  the  other  hand,  the  formation  of  fats  from  proteins  is 
apparently  impossible  in  the  cells  of  the  higher  animals,  and  the 
evidence  for  the  formation  of  sugar  from  fat  is  limited  to  the  study  of 
the  respiratory  quotient  in  hibernating''animals.  With  the  exception 
of  a  feW'  cases  quoted  by  Pfliiger  and  von  Noorden,  no^ support  for 
such  a  conversion  is  obtained  from  the  conditions  observed  in  the 
glycosuria  caused  by  the  administration  of  phloridzin  or  by  extirpation 
of  the  pancreas. 


CHAPTER  XII 

THE    BLOOD 

In  the  unicellular  animals  and  in  the  lowest  metazoa  the  cells  are 
bathed  by  the  medium  in  which  the  organisms  live,  and  are  therefore 
exposed  to  all  the  changes  in  the  composition  of  this  fluid  which 
may  be  brought  about  by  cosmic  events.  With  the  evolution  of  a 
body  cavity  filled  with  fluid  the  tissue-cells  are  set  free  from  the 
necessity  of  adapting  their  metabolism  to  wide  ranges  of  chemical 
composition,  being  bathed  by  an  internal  mediiun  which  is  maintained 
practically  constant  in  its  characters  for  any  given  type.  With 
increasing  differentiation  the  fluid  of  the  coelom,  which  may  be  called 
blood,  becomes  enclosed  in  branching  systems  of  tubes,  and  its  circula- 
tion is  provided  for  by  the  development  of  contractile  chambers  at 
some  point  or  points  of  the  tubes.  In  all  the  higher  animals,  the  blood, 
the  common  medium  and  means  of  exchange  for  all  parts  of  the  body, 
circulates  through  a  closed  system  of  tubes,  a  constant  flow  being  kept 
up  by  the  action  of  the  heart.  It  is  separated  from  the  tissue  elements 
themselves  by  the  walls  of  the  blood-vessels.  The  free  interchange  of 
material  between  blood  and  tissues  is  facilitated  by  the  tenuity  of  the 
vascular  wall.  The  interstices  of  the  tissues  contain  a  fluid,  the  '  tissue 
fluid,'  any  excess  of  which  is  drained  off  by  special  channels  known  as 
lymphatics  and  carried  back  to  the  blood.  Interchange  between  the 
blood  and  the  tissue-cells  can  be  effected  partly  by  diffusion,  partly 
by  a  direct  exudation  or  filtration  of  the  fluid  parts  of  the  blood  TNnth 
certain  of  its  constituents  through  the  capillary  walls.  Since  the 
function  of  the  blood  is  to  act  as  the  common  nutritive  medium  of  all 
parts  of  the  body,  it  has  to  convey  food  materials  from  the  digestive 
organs  and  oxygen  from  the  lungs  to  the  tissues.  From  these  it 
receives  in  exchange  their  waste  products,  namely,  carbon  dioxide 
and  the  results  of  nitrogenous  metabolism,  and  carries  them  away  to 
the  excretory  organs,  such  as  the  lungs  and  kidneys,  by  which  they 
are  eliminated.  It  is  evident  that  the  composition  of  the  blood  must 
vary  from  time  to  tin\e  and  place  to  place  accordiiig  to  the  condition 
of  activity  and  the  function  of  the  organ  which  it  is  traversing.  The 
organs  of  the  body  are  adjusted  to  respond  to  very  minute  changes 
in  the  composition  of  the  circulating  fluid,  and  add  to  or  subtract 
from  its  constituents  according  as  these  are  present  in  deficiency  or 

9ir> 


/ 


916  PHYSIOLOGY 

excess.  The  changes  are  therefore  kept  within  infinitesimal  limits  ; 
in  most  cases  they  are  within  the  limits  of  errors  of  analysis,  and  we 
may  therefore  treat  the  blood  as  a  fluid  of  approximately  constant 
composition  and  qualities. 

Blood  obtained  from  a  mammal  is  an  opaque  fluid  varying  in  tint 
according  to  the  vessel  from  which  it  is  derived,  being  scarlet  when 
taken  from  an  artery,  purplish  in  colour  when  taken  from  a  vein,  the 
difference  being  determined  by  the  degree  of  oxygenation  of  the  blood. 
On  shaking  venous  blood  with  air  it  takes  up  oxygen  and  acquires  the 
scarlet  colour  characteristic  of  arterial  blood.  If  examined  in  a  thin 
layer  under  the  microscope  its  opacity  is  seen  to  be  due  to  the  fact 

that  it  is  not  homogeneous,  but 
consists  of  a  number  of  corpus- 
cles of  different  kinds  suspended 
in  a  light  yellow  transparent 
fluid.  In  order  to  make  out  the 
characters  of  these  corpuscles 
the  blood  should  be  diluted  with 
some  '  normal '  fluid,  such  as 
0-9  per  cent,    sodium  chloride. 

Fig.   354.     Non-nucleated  red   blood-discs    ^^  '^  ^^^^n   seen    to    contain    two 
of   human   blood.     On  the  right  of  the    classes  of  COrpuScleS.     Much  the 

(fci  ViNCErxf ''  ^'^  '"'"  '"'  "'^^"•'^m©^  numerous  are  the  '  red  cor- 
puscles.' These  differ  in  appear- 
ance according  as  the  blood  is  derived  from  a  mammal  or  from  one  of 
the  lower  orders  of  vertebrates.  In  all  the  latter  it  is  a  nucleated  cell. 
In  the  frog,  for  instance,  it  is  an  oval  bi-convex  disc  containing  an  oval 
nucleus  in  the  centre.  In  man  and  other  mammals  the  red  corpuscle 
is  a  bi-concave  circular  disc  (Fig.  .35-3),  varying  in  size  in  different 
species.  The  average  sizes  of  the  corpuscles  in  man  are  given  in  the 
following  Table  : 

Diameter     .         .         .         .         .         7'1  to  78  ^ 
Thickness  (at  periphery)        .         .         25^ 
Thickness  (at  centre)    ...         10  to  20  ^ 

In  the  blood  of  man  there  is  an  average  of  five  million  red  blood- 
discs  in  every  cubic  millimetre  of  blood. 

The  other  kind  of  formed  element,  the  white  corpuscle,  or  leucocyte, 
is  present  in  much  smaller  numbers  than  the  red  corpuscle,  there 
being  in  human  blood  an  average  of  one  leucocyte  to  every  500  red 
corpuscles.  These  leucocytes  are  colourless  cells,  somewhat  larger 
than  the  red  blood-discs  of  man,  presenting  one  or  more  nuclei  and  a 
granular  or  hyaline  protoplasm.  When  examined  on  the  warm  stage 
they  are  seen  to  be  amoeboid,  and  many  of  them,  like  the  amoeba, 


THE  BLOOD  917 

have  the  power  of  ingesting  granules  of  carmine,  food,  or  dead  bacteria 
with  which  they  may  come  in  contact. 

In  addition  to  these  two  classes,  a  third  body  is  generally  described 
under  the  name  of  '  blood-platelets  '  or  hajmatoblasts.  These  are 
especially  well  seen  when  the  blood  has  been  received  directly  into  an 
excess  of  osmic  acid.  It  is  still  doubtful  whether  they  are  pre- 
existent  in  the  circulating  blood  or  are  formed  in  the  plasma  by  a 
process  of  precipitation. 

Unless  special  precautions  are  taken,  the  examination  of  blood 
obtained  from  a  blood-vessel  is  interfered  with  by  the  process  of 
clotting,  which  ensues  shortly  after  the  blood  has  left  the  blood- 


FiG.  3.54a.  Network  of  fibrin,  after  wasfiing  away  the  corpuscles  from  a  film 
of  blood  that  has  been  allowed  to  clot ;  many  of  the  filaments  radiate 
from  little  clumps  of  blood  platelets.     (Schafer.) 

vessels.  If  blood  be  received  into  a  beaker  it  is  at  first  perfectly  fluid, 
so  that  it  can  be  poured  from  one  vessel  to  another.  After  a  space  of 
time  varying  from  three  to  eight  minutes  it  begins  to  be  ^-iscous,  and 
if  poured  out  of  the  beaker  leaves  an  adherent  layer  on  the  sides  of 
the  vessel.  A  minute  later  the  whole  mass  of  the  blood  becomes  solid 
and  the  beaker  can  be  inverted  without  spilhng  its  contents.  If  a 
section  be  made  of  this  blood-clot  it  is  found  to  owe  its  solidity  to  a 
network  of  fine  threads  of  a  protein  substance  named  fibrin,  which 
have  formed  throughout  the  plasma  and  enclose  the  corpuscles  in  their 
meshes  (Fig.  354a).  On  leaving  the  clot  for  some  hours,  drops  of  yellow 
fluid  appear  on  its  surface  and  run  together.  The  whole  clot  contracts, 
and  finally  there  is  a  reduced  clot  floating  or  suspended  in  a  yelloA\-ish 
fluid  known  as  seriun.  If  after  the  blood  has  left  the  vessels  it  be 
whipped  with  a  bunch  of  twigs,  or  stirred  with  a  glass  rod,  the  filaments 
of  fibrin  as  they  are  formed  are  deposited  on  the  twigs.  After  three  or 
four  minutes  the  twigs  can  be  withdrawn  and  the  spongy  fibrin 
collected.  The  blood  which  is  left  consists  only  of  the  corpuscles, 
plus  serum,  and  will  not  clot,  since  its  fibrin  has  been  removed.  It  is 
known  as  defibrinated  blood.  Since  the  corpuscles  are  apparently 
unchanged  in  the  meshes  of  the  clot  and  clotting  can  be  produced  in 
blood-plasma  entirely  separated  from  corpuscles,  we  must  look  upon 
the  process  of  coagulation  as  determined  in  the  main  by  changes  in 
the  blood-plasma.  We  can  regard  the  blood  therefore  as  a  tissue 
consisting  of  a  fluid  matrix,  which  is  extremely  unstable  and  undergoes 
change  when  it  leaves  the  vessels,  and  as  having,  embedded  in  its 
matrix,  formed  elements  or  cells  of  various  kinds. 


SECTION  I 

THE   WHITE   BLOOD-CORPUSCLES 

Amoeboid  cells  are  a  constant  constituent  of  the  coelomic  fluid  in 
all  classes  of  animals.  Even  in  the  lower  metazoa,  where  there  is  not 
yet  a  body  cavity,  wandering  mesoderm  cells  are  present  which 
apparently  discharge  functions  analogous  in  all  respects  to  those  of 
the  white  blood-corpuscles  of  mammals.  On  carefully  examining  a 
specimen  of  human  blood,  either  fresh  or  in  the  form  of  a  thin  stained 
film,  several  varieties  of  these  cells  are  seen  to  be  present.  In  a  fresh 
specimen  we  can  distinguish  the  following  varieties  : 

(a)  A  cell  with  a  lobed  nucleus  and  finely  granular  protoplasm  ; 


Fig.  355.     Various  forms  of  leucocytes. 

a,  eosinophile  corpuscle  ;  h,  ordinary  polynuclear  leucocyte  ('  neutrophile  ' ) ; 

c,  hyaline  corpuscle  ;   d,  lymphocyte. 

{h)  A  small  cell  consisting  almost  entirely  of  a  nucleus  surrounded 
by  a  thin  layer  of  protoplasm  ; 

(c)    A  cell  with  a  single  nucleus  and  clear  hyaline  protoplasm  ; 

{d)  A  cell  with  a  lobed  or  reniform  nucleus,  the  cytoplasm  being 
beset  with  large  coarsely  refracting  granules. 

These  four  types  are  known  as  the  finely  granular  or  polymorpho- 
nuclear cell,  the  lymphocyte,  the  hyaline  corpuscle,  and  the  coarsely 
granular  corpuscle. 

The  differentiation  of  the  various  types  of  leucocytes  is  more 
easily  made  if  recourse  be  had  to  staining  with  mixtures  of  aniUne 
dyes.  This  method  was  introduced  by  Ehrlich,  who  classified 
leucocytes  according  to  the  staining  characters  of  their  granules, 
dividing  the  latter  into  : 

(a)  Those  staining  with  acid  dyes,  such  as  eosin — acidophile  or 
eosinophile  granulation  ; 

91S 


THE  WHITE  BLOOD-CORPUSCLES  919 

(6)  Those  staining  with  basic  dyes — basophile  ; 
(c)  Those  staining  only  with  a  mixture  of  the  acid  and  basic  dyes 
and  therefore  spoken  of  as  neutrophile. 

An  acid  dye  is  generally  a  salt  in  which  the  colouring-matter  plays  the  part  of 
an  acid  radical.  Thus  eosin  is  the  sodium  salt  of  the  coloured  acid  tetrabrom- 
fiuorcscoin.  Basic  dyes  possess  basic  colour  radicals.  An  example  of  this 
class,  mcthyleno  blue,  is  the  chloride  of  the  coloured  base  tetramothyldiphenthia- 
zine.  Neutral  dyes,  according  to  Ehrlich,  are  those  in  which  a  colour  base  is 
combined  with  a  colour  acid,  such  as  the  eosinate  of  methylene  blue,  or  the 
picrate  of  rosaniliae. 

Li  preparations  stained  with  mixtures  of  these  dyes  we  may 
distinguish  the  following  types  : 

(1)  The  polymorphonuclear  cells.  These  present  a  lobed  nucleus, 
and  their  protoplasm  contains  abundant  fine  neutrophile  granules. 
They  form  about  70  per  cent,  of  the  total  leucocytes.  If  the  specimen 
be  overstained  with  eosin  the  granules  may  take  on  a  red  stain. 

(la)  A  few  cells  are  sometimes  seen  with  a  horseshoe  or  hour-glass 
nucleus  and  presenting  a  few  neutrophile  granules.  These  are  spoken 
of  as  transitional  cells,  and  have  been  supposed  to  represent  an  inter- 
mediate stage  between  large  mononuclear  or  hyaUne  cells  and  the 
polymorphonuclear  leucocyte.  They  do  not  form  more  than  1  per 
cent,  of  the  leucocytes. 

(2)  The  lymphocytes  are  small  cells  Avith  a  romid  nucleus  sur- 
rounded by  a  thin  layer  of  hyahne  protoplasm  which  is  free  from 
granules.     These  form  23  per  cent,  of  the  leucocytes. 

(3)  Large  mononuclear  or  hyaline  corpuscles.  These  cells  are  two 
or  three  times  the  size  of  a  red  corpuscle,  and  possess  a  large  oval 
nucleus  which  stains  feebly  with  basic  dyes.  In  normal  blood  not 
more  than  2  per  cent,  of  the  leucocytes  are  of  this  type. 

(4)  In  every  well-stained  blood-film  the  eosinophil  corpuscle  is 
very  evident,  although  not  forming  more  than  3  per  cent,  of  the  white 
corpuscles.  The  nucleus  is  generally  single,  but  is  often  crescent- 
shaped  or  reniform.  The  protoplasm  is  crammed  with  large  discrete 
highly  refractive  granules  which  stain  deeply  with  eosin  and  give 
micro-chemical  reactions  for  iron  as  well  as  phosphorus.  The  granules, 
which  in  man,  dog,  and  rabbit  are  spherical,  are  cuboidal  in  the  horse, 
and  in  birds  have  the  shape  of  short  rods. 

(5)  A  cell  which  is  found  with  difficulty,  but  is  apparently  a  normal 
constituent  of  human  blood,  is  the  basophile  leucoc}i:e.  This,  which 
is  somewhat  smaller  than  the  polymorphonuclear  cell,  has  a  lobed  or 
tri-lobed  nucleus  and  presents  a  number  of  granules  in  its  protoplasm 
which  stain  deeply  with  basic  dyes.  It  is  sometimes  spoken  of  as  a 
*  Mast '  cell,  the  German  term  for  the  cell  being  used  without  transla- 
tion.    It  does  not  form  more  than  0-5  per  cent,  of  the  total  leucocytes 


920  PHYSIOLOGY 

of  the  blood.  The  granules  are  practically  invisible  in  fresh  specimens, 
in  this  respect  presenting  a  contrast  with  the  eosinophile  granules. 
The  leucocytes  as  a  whole  undergo  variations  in  number  according  to 
the  physiological  state  of  the  animal  and  are  increased  during  digestion, 
specially  of  a  protein  meal.  They  vary  from  one  in  300  to  one  in  600 
red  corpuscles,  or,  taken  as  a  whole,  from  18,000  to  36,000  per  cubic 
milhmetre  of  blood. 


FORMATION  OF  THE  LEUCOCYTES 

In  classifying  the  white  corpuscles  of  the  blood  it  is  essential  to 
know  whether  the  different  varieties  we  have  described  represent 
phases  in  one  and  the  same  corpuscle  or  a  number  of  different  cells  of 
separate  origin.  The  question  as  to  the  specificity  of  each  kind  of 
leucocyte  cannot  be  regarded  as  settled.  According  to  some  observers, 
Gulland  and  others,  all  the  leucocytes  are  derived  from  one  kind  of 
cell,  namely,  the  lymphocyte.  Ehrhch  and  his  school,  on  the  other 
hand,  regard  each  type  as  forming  a  tissue  sui  generis,  originating  in 
separate  localities  and  from  distinct  kinds  of  cells.  Since  division  of 
the  leucocytes  in  the  blood  itself  appears  to  be  an  occurrence  of  the 
utmost  rarity,  we  must  locate  the  original  seat  of  formation  of  these 
cells  in  two  tissues.  Lymphocytes  are  derived  from  the  adenoid 
tissue  forming  the  lymphatic  glands  and  the  lymph  nodules  surround- 
ing so  many  of  the  mucous  cavities.  These  lymphatic  nodules  present 
towards  their  centre  a  clearer  zone,  consisting  of  cells  rather  larger 
than  those  of  the  periphery  and  known  as  the  '  germ  centre.'  The 
nuclei  in  these  cells  present  a  well-marked  reticular  arrangement,  and 
nuclear  figures  are  often  to  be  seen.  By  the  division  of  these  cells 
lymphocytes  are  formed,  pushing  towards  the  periphery  of  the  nodule, 
where  they  make  their  way  into  the  Ijriiiph- sinus  and  are  carried 
slowly  by  the  lymph  into  the  blood.  Some  of  these  lymphocytes  may 
possibly  pass  directly  through  the  capillary  wall  into  the  blood-stream. 

The  other  tissue  concerned  in  the  formation  of  leucocytes  is  the 
bone-marrow.  This  is  the  chief  blood-forming  tissue  of  the  body, 
since  it  is  responsible  also  for  the  production  of  all  red  blood-corpuscles 
which  are  formed  during  adult  life.  In  the  red  marrow  are  seen  a 
number  of  cells  known  as  myelocytes.  These  contain  a  single  rounded 
nucleus  and  a  well-marked  protoplasm  which  may  be  non-granular  or 
may  contain  granules,  generally  eosinophile  in  character,  but  some- 
times basophile.  It  is  stated  that  all  intermediate  stages  are  to  be 
found  in  the  bone-marrow  between  these  '  myelocytes '  and  the 
polymorphonuclear  leucocyte  as  well  as  the  eosinophile  leucocyte.  It 
is  certain  that  in  the  disease  leuka;mia,  which  is  associated  with  an 
increased  number  of  leucocytes  in  the  blood,  there  may  be  an  increase 


THE  ^YHITE  BLOOD-CORPUSCLES  921 

either  of  eosinophile  cells  or  of  the  neutrophile  cells,  and  either  condi- 
tion is  associated  with  changes  in  the  red  bone-marrow.  We  may 
therefore  provisionally  arrange  the  leucocytes  of  the  blood  according 
to  their  origin  as  follows  : 

(1)  Small  hTnphocyte  derived  from  lymphoid  tissue. 

(2)  Large  mononuclear  or  hyaline  corpuscle  :  doubtful  whether 
derived  by  a  growth  of  (1)  or  from  a  myelocyte. 

{■i)  Pol}Tnorphonuclear  leucocyte  formed  in  bone-marrow. 

(4)  Eosinophile  cell  derived  from  similar  cells  in  the  bone-marrow. 
This  origin  of  the  eosinophile  corpuscle  is  rendered  more  probable  by 
the  fact  that  the  shape  of  the  granule,  which  differs  from  one  species 
to  another,  is  the  same  whether  the  cell  be  derived  from  the  blood  or 
the  bone-marrow. 

The  intermediate  or  transitional  cell  may  be  derived  either  from 
th^  lymphocyte  or  from  a  myelocyte.  Li  many  cases  of  leukaemia  the 
myelocyte  passes  into  the  blood  in  large  numbers  without  undergoing 
the  changes  necessary  to  convert  it  into  the  typical  blood-cell.  We 
find  then  mononuclear  cells  which  are  either  fie^  from  granules  or 
contain  eosinophile  or  basophile  granules. 


FUNCTIONS  OF  THE  LEUCOCYTES 

PHAGOCYTOSIS.  We  have  seen  that  the  leucocjtes  from  whatever 
animal  they  be  taken  present  two  phenomena.  \-iz.  that  of  amoeboid 
movement  and  that  of  ingesting  foreign  particles  which  may  be  pre- 
sented to  them.  On  account  of  this  power  of  eating  up  foreign 
particles  they  are  frequently  spoken  of  as  '  phagocytes,'  in  this  respect 
resembhng  unicellular  organisms  and  the  undifferentiated  cells  of 
many  kinds  of  tissue.  AU  the  phenomena  connected  with  the  process 
of  inflammation  in  higher  animals  are  directed  to  the  assemblage  of 
leucocytes  at  the  spot  which  is  the  seat  of  injury  or  of  infection,  so 
that  they  may  devour  and  remove  either  the  injured  tissue  or  the 
invading  micro-organisms.  This  process  plays  therefore  an  important 
part  in  determining  the  immunity  of  any  animal  against  infection  ; 
though  in  the  higher  animals  it  is  assisted  by  a  number  of  other 
mechanisms  directed  towards  the  same  end,  which  we  shall  have  to 
discuss  in  a  subsequent  chapter.  The  use  of  phagocytosis  is  not, 
however,  confined  to  the  protection  of  the  organism  against  infection. 
Wherever  any  effete  or  dead  tissue  has  to  be  cleared  away,  whether  as 
the  result  of  injury  or  in  the  course  of  metamorphosis  of  organs,  the 
leucocytes  play  an  important  part.  Thus  in  the  great  rearrangement 
of  tivssues  which  occurs  in  the  larval  state  of  insects,  the  removal  of  the 
muscle  fibres  which  are  no  longer  required  is  effected  by  the  accu- 
mulation of  phagocytes  around  them.      The  phagocytes  may  send 


922  PHYSIOLOGY 

processes  into  the  muscle  substance,  which  dissolve  this  tissue  and  then 
take  it  up.  The  absorption  of  the  tail  of  the  tadpole  is  effected  in  the 
same  way  by  means  of  phagocytes.  In  mammals,  including  man,  the 
moulding  of  the  long  bone  which  occurs  in  the  process  of  growth  is 
effected  by  continual  and  coincident  processes  of  absorption  and 
new  formation  of  bone.  The  absorption  is  carried  out  by  means  of 
special  phagocytes  formed  by  the  aggregation  of  a  number  of  leucocytes, 
the  well-known  '  giant  cells  '  or  myeloplaxes  which  form  so  prominent 
a  constituent  of  bone-marrow. 

The  blood-corpuscles  represent  the  wandering  phagocytes  of  the 
body.  There  are  fixed  phagocytes  of  which  the  myeloplaxes  just 
mentioned  may  be  regarded  as  a  type.  Other  members  of  this  class 
are  the  endothelial  cells  (Kupfer's  '  Sternzellen ')  which  line  the 
capillaries  of  the  liver.  If  a  suspension  of  carmine  or  of  micro- 
organisms be  injected  into  the  blood  stream  these  endothelial 
cells  are  found  a  little  later  to  have  taken  up  large  numbers  of 
the  foreign  bodies.  Under  normal  circmustances  these  cells  as  well 
as  some  similar  cells  in  the  spleen  take  up  effete  red  blood-corpuscles 
and  destroy  them.  During  the  process  of  degeneration  of  a  peripheral 
nerve  brought  about  by  its  separation  from  the  gangUon-cells  of  which 
its  fibres  are  the  processes,  a  marked  prohferation  of  the  nerve-nuclei 
takes  place.  These  become  surrounded  with  protoplasm  and  act  the 
part  of  phagocytes,  loading  themselves  with  the  fat  globules  set  free 
by  the  degeneration  of  the  myelin  sheath.  To  the  same  class  of  fixed 
phagocytes  may  possibly  be  ascribed  certain  of  the  plasma-cells  of  the 
connective  tissues. 

That  the  polymorphonuclear  leucocytes  are  endowed  with  these 
phagocytic  properties  is  universally  acknowledged,  but  some  doubt 
still  exists  as  to  how  far  the  other  types  of  leucocytes  which  we  have 
described  can  function  as  phagocytes.  It  is  probable  that  the  lympho- 
cytes, and  certainly  the  large  mononuclear  or  hyahne  corpuscles,  are 
endowed  with  these  properties.  The  granular  corpuscles,  namely, 
eosinophile  and  basophile,  are  thought  by  some  to  function  as  uni- 
cellular glands  and  to  react  to  infection,  not  by  englobing  the  micro- 
organisms, but  by  discharging  substances  stored  up  in  their  granules 
which  have  a  poisonous  effect  on  the  micro-organisms.,  and  so  prepare 
them  for  subsequent  ingestion  by  the  polymorphonuclear  leucocytes. 

The  other  functions  which  have  been  ascribed  to  leucocytes  are 
unimportant  as  compared  with  their  role  as  phagocytes,  and  are  all 
of  them  questionable.  Thus  some  authors  ascribe  to  leucocytes  an 
important  part  in  the  taking  up  of  fat  from  the  intestine  and  its 
carriage  into  the  lymphatic  system.  In  the  coagulation  of  the  blood 
the  leucocytes  have  been  supposed  to  act  by  the  discharge  of  sub- 
stances which  may  act  as  precursors  of  the  fibrin  ferment.     In  the 


THE  WHITE  BLOOD-CORPUSCLES  923 

invertebrata  the  wandering  mesoderm  cells  ot  only  remove  the 
injured  tissue  but  apparently  give  rise  to  new  connective  tissues.  The 
same  function  was  formerly  assigned  to  the  leucocytes  of  maimnals  by 
Ziegler,  and  Metchnikoff  still  believes  that  after  the  removal  of  any 
injured  tissue  the  emigrated  leucocytes  undergo  elongation  to  form 
so-called  fibroblasts,  by  the  further  division  of  which  are  produced 
the  white  fibres  of  the  connective  tissues  as  well  as  the  branched 
connective-tissue  cells.  Most  authors  at  the  present  time  have  come 
to  the  conclusion  that  the  work  of  the  leucocytes  is  complete  with  the 
removal  of  dead  or  injured  tissue,  and  that  the  process  of  regeneration 
is  carried  out  by  the  plasma-cells  of  the  connective  tissue,  which 
enlarge,  undergo  division,  and  form  the  fibroblasts  of  the  developing 
tissue.  These  plasma-cells  can  change  their  position  and  act  as  phago- 
cytes,eating  up  and  digesting  the  polymorphonuclear  leucocytes  which 
have  prepared  the  way  for  their  regenerative  activity.  Their  amoeboid 
power  is  shown  by  the  fact  that  if  two  sterile  cover-glasses  be  introduced 
under  the  skin,  new  connective  tissue  is  formed  between  the  cover- 
glasses,  and  this  method  has  been  adopted  by  Ziegler  for  the  study  of 
the  cellular  changes  involved  in  the  new  regeneration  of  this  tissue. 


SECTION  II 

THE   RED   BLOOD-CORPUSCLES 

^  The  red  blood-corpuscles,  or  erythrocytes,  in  man  and  in  mammals 
'  ^  a^e  nucleated  bi-concave  discs,  about  7  to  8/x  (^^^qo  in.)  in  diameter 
and  about  one-third  of  this  in  thickness.  The  colour  of  a  single 
corpuscle  when  viewed  under  the  microscope  is  yellow,  the  red  colour 
being  only  apparent  when  larger  numbers  are  seen  together.  The 
red  corpuscles  form  about  50  per  cent,  of  the  total  mass  of  the  blood, 
there  being  about  5,000,000  red  corpuscles  in  every  cubic  millimetre 
of  blood.  They  are  soft,  flexible,  and  elastic,  so  that  they  can 
readily  squeeze  through  apertures  and  canals  narrower  than  them- 
selves without  undergoing  permanent  distortion.  Each  red  corpuscle 
consists  of  a  framework  or  stroma,  composed  chiefly  of  protein 
material,  containing  in  its  meshes  or  in  a  state  of  loose  chemical 
combination  a  red  colouring-matter,  haemoglobin,  to  which  is  due  the 
colour  of  the  corpuscles  and  of  the  blood  itself. 

It  is  only  in  mammalia  that  the  red  corpuscles  are  of  the  character 
described.  In  the  camel  they  are  oval  in  shape,  but  otherwise  resemble 
the  corpuscles  of  other  mammals.  In  all  other  classes  of  vertebrata 
the  red  corpuscles  are  oval,  nucleated  cells.  The  haemoglobin  is 
diffused  through  the  protoplasm  of  the  cell-body  and  does  not  extend 
to  the  nucleus.  During  the  early  part  of  foetal  life  the  corpuscles  of 
mammals  are  also  nucleated,  but  in  the  adult  condition  the  erythro- 
cytes, except  under  abnormal  conditions,  lose  all  traces  of  the  nucleus 
before  entering  the  blood  stream.  The  small  size  and  great  number  of 
the  red  corpuscles  determine  that  a  very  large  area  of  surface  of  red 
corpuscles  is  exposed  to  the  plasma.  The  volume  of  each  corpuscle  has 
been  estimarted  as  -0000000722  mm.^  and  its  surface  as  -000128  mm.^, 
so  that  the  total  surface  of  red  corpuscles  in  the  blood  of  a  man 
weighing  about  70  kilos  (assuming  his  total  blood  as  ^l^  of  the  body 
weight)  would  be  about  3000  sq.  metres,  or  1500  times  the  surface  of 
the  body  itself.  This  great  extent  of  surface  is  of  importan  e  in 
facihtating  the  exchange  of  material,  especially  oxygen,  between  the 
corpuscle  itself  and  the  surrounding  plasma. 

On  treating  the  blood  with  weak  solutions  of  tannic  or  boracic 
acid  a  separation  occurs  between  the  haemoglobin  and  the  stroma,  the 
former  appearing  as  a  small  ball  near  the  centre  of  a  colourless  disc 

924 


THE  RED  BL00D-C0RPUSCLE8  925 

or  being  extruded  so  as  ^o  lie  just  outside  the  stroma.  Briicke.  who 
first  observed  this  appearance,  gave  the  name  of  '  zooid  '  to  the  mass 
of  hemoglobin  and  of  '  03Coid  '  to  the  stroma. 

OSMOTIC  RELATIONSHIPS  OF  THE  RED  CORPUSCLE.  Jf 
the  blood-plasma  be  concentrated  by  evaporation  or  by  the  addition 
of  neutral  salts  its  osmotic  pressure  rises  and  water  diffuses  from  the 
corpuscles  into  the  plasma  in  order  to  equalise  the  osmotic  pressure 
within  and  without  the  corpuscle.  The  latter  therefore  becomes 
wiiukled  or  crenated.  On  the  other  hand,  dilution  of  the  plasma 
diminishes  its  osmotic  pressure  below  that  of  the  corpuscle,  and  water 
therefore  passes  into  the  latter,  which  swell  up  and  become  spherical, 
and  if  the  plasma  be  made  sufficiently  dilute  the  corpuscles  burst  with 
the  liberation  of  the  haemoglobin  they  contain.  The  corpuscles  of 
mammalian  blood  neither  gain  nor  lose  volume  in  a  solution  containing 
0'9  per  cent,  sodium  chloride.  The  osmotic  pressure,  as  determined 
by  the  freezing-point,  of  such  a  solution  is  identical  with  that  of  the 
blood.  For  frogs'  blood  such  a  solution  would  be  too  concentrated 
and  bring  about  crenation.  The  salt  solution  which  is  normal  for 
frogs'  blood  only  contains  0"65  per  cent,  sodium  chloride. 

Although  the  average  molecular  concentration  of  blood-plasma  m  mammals 
is  equivalent  to  that  of  a  0-9  per  cent,  sodium  chloride  solution,  it  may  vary  even 
in  one  animal  within  fairly  wide  limits,  as  is  shoA\ia  by  the  following  deter- 
minations of  the  freezing-point  of  blood-serum  taken  from  animals  \inder  various 
circumstances  : 

Man  (healthy) -0-56  to  -0-600 

Dog -0-55  to  -0-04.5 

Ox -0-55  to  -0-6()2 

Rabbit -0-55  to  -0-620 

The  behaviour  of  the  red  corpuscles  when  immersed  in  solutions 
of  sodium  chloride  of  different  concentrations  shows  that  its  limiting 
membrane  or  most  external  layer  is  impermeable  to  sodium  chloride. 
If  this  salt  be  added  to  defribinated  blood  and  the  crenated  corpuscles 
separated  by  the  centrifuge,  practically  the  whole  of  the  added  sodium 
chloride  remains  in  the  plasma  or  serum.  The  red  corpuscle  is 
impermeable  to  most  neutral  salts  as  well  as  to  cane  sugar  and  glucose. 
We  may  therefore  make  '  normal '  solutions  with  sodium  chloride, 
sodium  sulphate,  potassium  nitrate,  or  cane  sugar,  taking  care  that 
each  of  the  solutions  shall  be  isotonic  with  a  0-9  per  cent,  solution  of 
sodium  chloride.  On  the  other  hand,  a  solution  of  urea  behaves 
towards  the  corpuscles  like  distilled  water.  Tf  some  red  corpuscles 
be  added  to  a  1  per  cent,  solution  of  urea  in  noinial  salt  solution,  they 
neither  shrink  nor  swell,  and  if  the  mixture  be  centrifuged  and  the 
corpuscles  and  supernatant  fluid  examined  separately,  the  percentage 
of  urea  in  the  two  cases  will  be  found  identical,  though  there  would 


92()  PHYSIOLOGY 

be  a  great  preponderance  of  sodium  chloride  in  the  supernatant  fluid. 
If  a  1  or  2  per  cent,  solution  of  urea  in  water  be  added  to  defibrinated 
blood,  the  corpuscles  will  swell  up  and  burst  just  as  if  distilled  water 
had  been  added.  There  are  a  large  number  of  substances  to  which 
the  corpuscles  are  permeable,  e.g.  alcohol,  chloroform,  ether,  &c.  In 
their  permeability  the  corpuscles  resemble  most  other  vegetable  and 
animal  cells  in  permitting  the  passage  of  all  those  substances  which 
are  soluble  in  fats  and  the  allied  substances,  cholesterin,  lecithin,  and 
protagon,  which  are  invariable  constituents  of  all  living  cells.  Accord- 
ing to  Overton  the  external  limiting  pellicle  of  the  red  corpuscles,  as 
in  most  living  cells,  is  formed  by  a  lecithin- cholesterin  compound, 
whose  solvent  power  determines  the  permeability  of  the  cell  by  foreign 
substances.  If  therefore  we  wish  to  stain  the  living  cell  we  must 
choose  some  dyestuff,  such  as  methylene  blue  or  neutral  red,  which  is 
soluble  in  such  lipoid  bodies. 

CHEMISTRY  OF  THE   RED  BLOOD-CORPUSCLES 

The  red  corpuscles  consist  of  two  parts,  haemoglobin  and  stroma, 
probably  in  a  state  of  loose  chemical  combination.  By  various  means 
it  is  possible  to  destroy  this  combination  and  to  dissolve  out  the 
haemoglobin,  leaving  the  colourless  swollen-up  stroma  floating  in  the 
plasma.  At  the  same  time  the  blood  becomes  darker  but  more 
transparent,  and  is  spoken  of  as  '  laked  '  blood. 

It  has  beeu  thought  by  Schwann,  Schafer,  and  others  that  the  red  corpuscle 
consists  of  a  solution  of  htemoglobin  contained  within  an  envelope  which  contains 
lecithin  and  cholesterin  and  forms  the  stroma.  Though  the  haemoglobin  can 
be  separated  from  the  stroma  by  very  simple  means,  it  is  difficult  to  believe 
that  it  is  in  watery  solution.  Thus  the  blood-corpuscles  contain  a  greater 
percentage  of  solids  than  any  soft  tissue  of  the  body.  The  blood-cor- 
puscles contain  36-7  per  cent,  solids,  as  against  muscular  tissue  with  25  per 
cent,  or  nervous  with  22  per  cent,  solids.  Of  these  solids,  95  per  cent, 
consist  of  haemoglobin,  so  that  the  solution  would  have  to  contain  at  least 
30  per  cent,  haemoglobin.  No  solution  of  haemoglobin  of  this  strength  can  be 
prepared.  In  many  animals,  such  as  the  rat  and  guinea-pig,  it  is  sufficient 
merely  to  'lake'  the  blood,  i.e.  to  bring  the  haemoglobin  into  solution  with  the 
surrounding  plasma  or  serum,  in  order  to  make  the  haemoglobin  crystallise  out. 
Some  form  of  combination  is  therefore  necessary  in  corpuscles  if  merely  to 
keep  the  haemoglobin  from  separating  out  in  a  crystalline  form. 

Blood  may  be  '  laked  '  by  any  of  the  following  means  : 
(a)  Addition  of  a  small  amount  of  ether. 
(6)  Free  dilution  ^nth  water, 
(c)  Alternate  freezing  and  thawing  of  the  blood. 
{d)  Addition  of  bile-salts. 

(e)  The  action  of  foreign  blood-serum  or  of  various  haemolysins 
whose  nature  we  shall  have  to  discuss  later. 


THE  RED  BLOOD-OORPUSCLES  927 

From  such  laked  blood  we  may  prepare  either  haGinoglobin  or 
stroma. 

PREPARATION  AND  PROPERTIES  OF  THE  STROMA.  In  order 
to  separate  the  stroma  from  the  haemoglobin,  blood  which  has  been 
defibrinated  or  prevented  from  clotting  by  the  addition  of  a  little 
sodium  oxalate  is  centrifuged  until  all  the  formed  elements  form 
a  solid  cake  at  the  bottom  of  the  tube.  The  tube  is  then  filled  up 
with  normal  saline  fluid  and  again  centrifuged,  and  this  process 
repeated  twice  in  order  to  wash  away  adherent  plasma  or  serum. 
After  the  final  washing  two  volumes  of  distilled  water  saturated  with. 
ether  are  added  to  one  volume  of  caked  corpuscles.  The  corpuscles 
swell  up  and  their  haemoglobin  passes  into  solution  into  the  surround- 
ing fluid.  The  blood  is  laked.  The  fluid  is  once  more  centrifuged  in 
order  to  throw  down  white  blood-corpuscles.  A  1  per  cent,  solution 
of  acid  sodium  sulphate  is  now  added  drop  by  drop  until  the  solution 
acquires  the  opaque  appearance  presented  by  ordinary  blood.  The 
action  of  this  salt,  as  of  dilute  acids,  is  to  precipitate  the  swoUen-up 
stromata,  which  reacquire  the  power  of  reflecting  light  from  their 
surfaces  and  restore  the  opacity  to  the  blood.  On  centrifuging,  the 
stromata  are  thrown  down,  and  can  be  collected  and  washed  with 
distilled  water  several  times  on  the  centrifuge.  The  stroma  protein 
only  forms  about  4  per  cent,  of  the  total  solids  of  the  corpuscle.  It  is 
insoluble  in  dilute  acids,  but  easily  soluble  in  dilute  alkalies.  On 
gastric  digestion  the  greater  part  dissolves,  leaving  a  residue  which  is 
rich  in  phosphorus,  and  has  been  called  nuclein.  Stroma  protein  is 
therefore  spoken  of  as  a  nucleo-protein.  Wooldridge,  who  devised 
the  method  given  above  for  the  preparation  of  pure  stromata,  regarded 
the  protein  as  a  compound  of  protein  and  lecithin.  The  substance 
certainly  contains  a  large  quantity  of  lecithin,  the  greater  part  of 
which  is  present  in  the  precipitate  obtained  on  gastric  digestion. 
According  to  Wright  the  nuclein  residue  jnelds  purine  bases  on 
hydrolysis,  and  is  therefore  rightly  classed  with  the  other  nucleins 
from  tissue-cells  and  contained  in  nuclei. 

PREPARATION  AND  PROPERTIES  OF  OXYHEMOGLOBIN. 
From  the  laked  solution  of  corpuscles  oxyhaemoglobin  can  be 
obtained  in  a  crystalline  form  with  varying  readiness  according  to  the 
animal  from  which  the  blood  is  derived.  Thus  in  the  case  of  the  rat, 
the  guinea-pig,  the  dog,  and  the  horse  it  is  sufficient  merely  to  cool  the 
laked  blood,  preferably  in  a  freezing  mixture  to  about  —10"  C.  in 
order  to  obtain  a  large  crop  of  ha3nioglobin  crystals.  Crystalhsation 
is  facilitated  b)'  the  addition  of  25  per  cent,  of  absolute  alcohol  to  the 
mixture,  though  the  use  of  alcohol  certainly  tends  to  interfere  with 
the  subsequent  purification  and  solubihty  of  the  ha)moglobin.  Oxy- 
hsemoglobin  can  be  recrystallised  by  dissolving  it  in  weak  alkali  at 


928 


PHYSIOLOGY 


35  "■  C,  cooling  the  solution  to  0°  C,  and  then  adding  cold  alcohol 
to  25  per  cent,  and  allowing  the  mixture  to  stand  for  some  days  at  a 
temperature  of  —5^  to  — 10°  C.  In  the  case  of  those  bloods  which 
yield  oxyhaemoglobin  crystals  with  greater  difficulty,  it  is  better  to 
add  to  the  laked  blood  an  equal  volume  of  a  saturated  solution  of 
ammonium  sulphate.  The  precipitate  of  globuHns  is  filtered  off  and 
the  filtrate  allowed  to  stand  in  a  cool  place.  Crystals  of  haemoglobin 
then  come  down  in  quantity. 

The  crystals  thus  obtained  are  as  a  rule  microscopic  in  size.     Most 


Fig.  356.     Crj'stals  of  oxyhsemoglob'n. 
1.  From  rat.     2.  From  guinea-pig.     3.  From  squirrel. 

animals  yield  an  oxyhaemoglobin  which  crystalUses  in  rhombic 
prisms  or  needles  belonging  to  the  rhombic  system.  In  the 
guinea-pig  the  crystals  are  tetrahedral  in  form,  while  the  oxyhsemo- 
globin  of  the  squirrel  crystalhses  normally  in  the  form  of  six-sided 
plates.  On  recrystalUsation,  however,  a  squirrel's  hsemogiobin  can 
be  obtained  as  a  mixture  of  rhombic  prisms  with  rhombic  tetrahedra. 
The  water  of  crystallisation  of  oxyhsemogiobin  varies  in  different 
animals  between  3  and  9  per  cent.  The  solubihty  of  the  crystals 
differs  according  to  the  animal  from  which  they  have  been  derived, 
and  is  in  direct  proportion  to  the  difficulty  with,  which  the  crystals 
are  obtained.  They  are  more  soluble  in  highly  diluted  solutions  of 
ammonia  and  the  caustic  alkahes  and  their  carbonates  than  in  water. 
A  solution  of  haemoglobin  will  not  diffuse  through  parchment  paper ; 
the  elementary  analysis  of  oxyhaemoglobin  crystals  gives  somewhat 
varying  results  according  to  the  animal  employed.  In  the  case  of  the 
oxyhaemoglobin  of  the  dog  Jaquet  obtained  the  following  figures  : 


C 
H 

N 
Fe 

S  . 

o 


63-91 
6-62 

15-98 
0-333 
0-54 

22-62 


In  100  parts 


The  chief  differences  between   different   anima 


54-97 
7-22 

16-38 
0-336 
0-568 

20-93 


s  appear  to  have 


relation  to  the  sulphur.     Haemoglobin  from  the  hen  contains  C-857  per 


Fe  per  cent. 

Authority 

0-336 

Jaquet. 

0-335 

Zinoffsky. 

0-336 

Hiifner. 

0-336 

Jaquet. 

THE  RED  BLOOD-CORPUSCLES  929 

cent,  sulphur.     All  specimens  are  alike  in  containing  a  constant  pro- 
portion of  iron,  as  is  shown  in  the  following  Table  : 

Oxj'hajraoglobin  of 

Dog 

Horse       .... 

Ox 

Hen  ...  . 

On  the  assumption  that  each  molecule  of  oxyhsemoglobin  contains 
one  atom  of  iron,  its  molecular  weight  would  be  1(3,660,  and  this 
result  is  borne  out  by  the  volume  of  oxygen  or  carbonic  oxide  which 
can  enter  into  combination  with  haemoglobin.     It  has  been  suggested 
by  Bunge  that  the  enormous  size  of  the  haemoglobin  molecule  finds  a 
teleological  explanation  ;    if  we  consider  that  iron  is  eight  times  as 
heavy  as  water,  a  compound  which  would  float  easily  along  with  the 
blood-current  through  the  vessels  could  only  be  secured  by  the  iron 
being  taken  up  by  so  large  an  organic  molecule.     Oxyhsemoglobin  is 
a  compound  in  definite  proportions  of  oxygen  and  haemoglobin  or 
reduced  haemoglobin.     It  can  be  easily  dissociated  and  is  split  up  by 
such  simple  means  as  exposure  to  a  vacuum.     If.  for  instance,  some 
arterial  blood  or  solution  of  oxyhaemoglobin  be  introduced  into  a 
Torricellian  vacuum,  the  fluid  is  seen  to  give  ofl  bubbles  of  gas,  and 
the  colour  changes  from  a  brilliant  scarlet  to  a  dull  bluish  red.     In 
this  process  each  gramme  of  .oxyhaemoglobin  gives  off  1-34  c.c.  of  oxygen. 
The  same  change  can  be  effected  by  treating  a  solution  of  oxyhaemo- 
globin with  reducing  agents  such  as  an  alkaline  solution  of  ferrous 
tartrate  (Stokes's  fluid)  or  ammonium  sulphide  ;    in  the  latter  case 
reduction  is  aided  by  gently  warming  the  solution.     Another  reagent 
of  value  for  effecting  the  reduction  of  oxyhaemoglobin  is  a  solution  of 
hydrazine.    The  oxygen  in  oxyhaemoglobin  can  be  replaced  by  equiva- 
lent quantities  of  other  gases.     Thus  if  carbon  monoxide  gas  be  led 
through  a  solution  of  oxyhaemoglobin,  oxygen  is  given  off  and  its 
place  is  taken  by  an  equal  volume  of  carbon  monoxide  with  the  forma- 
tion of  a  more  stable  compound,  carbonic  oxide  haemoglobin.     This 
body  is  only  dissociated  with  extreme  slowness  and  is  unaffected  by 
the  addition  of  reducing  agents.     By  using  special  precautions  to 
prevent  oxidation  of  the  gas  the  carbon  monoxide  can  be  replaced  in 
this  compomid  by  nitric  oxide,  NO.     We  have  therefore  a  series  of 
three  compounds  which  can  be  arranged  in  order  of  stability,  thus  : 

NO  -haemoglobin. 

CO  -haemoglobin. 

Og-hannoglobin. 

The  poisonous  properties  of  carbon  monoxide  are  due  to  its  power  of 
turning  out  the  oxygen  from  the  oxyhaemoglobin,  thus  depriving  the 

59 


930 


PHYSIOLOGY 


tissues  of  the  oxygen  which  is  normally  carried  to  them  by  the  red 
corpuscles. 

Haemoglobin  and  its  derivatives  give  well-marked  absorption 
spectra.  Thus  dilute  solutions  of  oxyhsemoglobin  placed  in  front 
of  the  slit  of  a  spectroscope  show  two  well-marked  absorption  bands 
between  Fraunhofer's  lines  D  and  E.  The  centre  of  the  band  nearest 
to  D  corresponds  to  A.  579,  and  is  often  spoken  of  as  the  band  a. 


Fig.  357.     The  spectra  of  oxyhsemoglobin  in  ditierent  grades  of  concentration, 
of   (reduced)  haemoglobin,  and  of  carbonic  oxide  haemoglobin.       (After 
Preyer  and  Gamgee.) 
1  to  4.   Solution  of  oxyhsemoglobin  containing    (1)  less    than   -01    per 
cent.,   (2)   -09  per   cent.,   (3)  -37   per  cent.,  (4)  -8   per  cent.     5.  Solution  of 
(reduced)    haemoglobin    containing    about     -2    per    cent.      6.    Solution    of 
carbonic  oxide  haemoglobin.      In  each  of  the  six  cases  the  layer  brought 
before  the  spectroscope  was  1  cm.  in  thickness.     The  letters  (A,  a,  &c.)  in- 
dicate Fraunhofer's  lines  and  the  figures  wave-lengths  expressed  in  yoTiVuiT 
millimetre. 


while  the  second  band,  the  one  next  to  E,  which  can  be  called  the 
band  /3,  is  broader,  has  less  sharply  defined  edges,  and  its  centre 
corresponds  approximately  to  X  554.  On  concentrating  the  solution 
or  using  thicker  layers  a  point  is  reached  at  which  the  two  bands  fuse 
into  one,  and  with  a  still  stronger  solution  it  will  be  found  that  the 
whole  of  the  spectrum  is  absorbed  with  the  exception  of  the  red  end. 

The  above  figure  shows  the  spectrum  of  oxyhajmoglobin  in  vary- 
ing concentrations,  a  stratum  one  centimetre  thick  being  examined. 
If  a  reducing  agent  be  added  to  the  solution  of  oxyhsemoglobin 
the  two  bands  disappear  and  their  place  is  taken  by  a  more 
diffuse  band  lying  midway  between  the  two  (Fig.  357,  5),  its 
centre  corresponding  to  X  555.  This  is  the  absorption  spectrum  of 
haemoglobin    or   reduced   haemoglobin.     The    spectrum    of   carboxy- 


THE  RED  BLOOD-CORPUSCLES  931 

haemoglobin  is  very  similar  to  that  of  oxyhsemoglobin,  the  bands, 
however,  being  shifted  slightly  towards  the  red  end.  This  solution  is 
of  a  brighter  red  than  oxyhaemoglobin.  Its  tint  is  best  observed  on 
diluting  the  blood  to  a  large  extent,  when  oxyhaemoglobin  acquires  a 
yellowish  tint,  while  the  pink  colour  of  CO-haemoglobin  is  retained  so 
long  as  any  colour  is  visible.  The  fact  that  CO-haemoglobin  is  not 
altered  by  reducing  agents  can  be  shown  by  adding  ammonium  sulphide 
to  CO-haemoglobin  and  examining  ^\'ith  the  spectroscope,  when  no 
change  is  observed. 

All  these  derivatives  of  haemoglobin,  besides  their  absorption  bands  in  the 
visible  spectrum,  have  characteristic  absorption  of  light  in  the  ultra-violet 
spectrum,  as  has  been  showTi  by  Gamgee.  In  the  case  of  oxyhaemoglobin  this 
absorption  causes  a  band  (Soret's  band)  which  occupies  the  greater  part  of  the 
spectral  region  between  Fraunhofer's  lines  G  and  H.  In  reduced  haemoglobin  this 
band  is  displaced  towards  the  visible  part  of  the  spectrum. 

Another  compound  of  haemoglobin  with  oxygen  is  methcemoglohin. 
This  substance,  although  not  of  normal  occurrence  in  the  body,  is 
found  in  urine  and  in  blood  whenever  there  is  a  sudden  breaking  down 
of  red  blood-corpuscles  with  the  setting  free  of  haemoglobin  in  the 
blood-plasma.  It  may  be  prepared  by  the  addition  of  a  ferricyanide, 
permanganate,  or  nitrite,  or  other  oxidising  or  reducing  agents  to  the 
laked  blood  or  to  solutions  of  oxyhaemoglobin.  It  is  a  chocolate-brown 
substance,  crystalUsable,  and  gives  a  distinct  absorption  band  in  the 
red  between  Fraunhofer's  lines  C  and  D.  It  is  unaltered  by  exposure 
to  a  vacuum.  On  treatment  with  reducing  agents,  however,  such  as 
Stokes's  fluid,  the  methaemoglobin  is  converted  into  haemoglobin,  from 
which  by  shaking  with  air  oxyhaemoglobin  can  be  re-formed.  The 
fact  that  methaemoglobin  cannot  be  reduced  by  exposure  to  a  vacuum 
indicates  that  it  is  a  compound  of  oxygen  with  haemoglobin  in  which 
the  oxygen  is  in  a  different  state  of  combination.  It  has  been  suggested 
by  Haldane  that  whereas  the  formula  of  oxyhaemoglobin  may  be 

/^ 
Hb\    I 

^0 


methaemoglobin  would  have  the  more  stable  composition 

.0 

'^0 


Hb^ 


The  change  from  oxyhaemoglobin  to  methaemoglobin  is  not  efTected, 
however,  by  a  simple  shifting  of  the  oxygen  groups,  but  must  be 
assumed  to  involve  two  distinct  events.  The  whole  of  the  oxygen  in 
loose  combination  with  haemoglobin  is  given  off,  and  the  oxygen  in  the 


932  PHYSIOLOGY 

methaemoglobin  molecule  is  derived  from  the  oxidising  agent  added, 
so  that  ferricyanide  of  potash,  for  instance,  is  converted  into  ferro- 
cyanide.*  Since  the  whole  of  the  oxygen  in  the  oxyhsemoglobin  is 
given  off  on  the  addition  of  potassimn  ferricyanide,  we  may  use  this 
fact  in  order  to  determine  the  total  amount  of  oxygen  in  combination 
in  the  blood  {v.  p.  969). 

DERIVATIVES  OF  HEMOGLOBIN.  Haemoglobin  is  a  compound 
of  an  iron-containing  coloured  group  (the  prosthetic  group)  with 
a  protein,  which  probably  varies  somewhat  in  different  animals. 
The  prosthetic  group  is  identical  in  every  case  where  it  has  been 
examined.  A  separation  of  the  prosthetic  group  from  the  protein 
moiety  can  be  efiected  with  extreme  ease,  and  occurs  whenever 
the  heemoglobin  is  treated  with  weak  acids,  with  alkalies,  or  is 
heated  above  70°  C.  The  protein  group  is  known  as  giobin.  In 
order  to  separate  this,  oxyhsemoglobin  crystals  are  dissolved  in 
water  and  treated  with  small  quantities  of  very  dilute  hydrochloric 
acid.  A  precipitate  of  pigment  forms,  which,  if  the  haemoglobin 
used  be  free  from  inorganic  salt,  rapidly  dissolves  in  excess  of  the  acid. 
Alcohol  and  ether  are  then  added  in  such  relative  quantities  that  the 
ether  separates  rapidly  from  the  aqueous  solution.  The  colouring- 
matter  (hsematin)  dissolves  in  the  ether,  whilst  the  protein  (giobin) 
remains  in  solution  in  the  water.  The  solutions  are  separated  by  a 
separating  funnel  and  ammonia  added  carefully  to  the  aqueous  solu- 
tion. This  throws  down  a  precipitate  of  the  protein,  which  is  soluble 
in  acids  and  alkahes  and  coagulable  on  heating ;  the  coagulum,  how- 
ever, is  soluble  in  acids.  It  is  precipitated  by  ammonia  in  the  presence 
of  ammonium  chloride.  It  contains  as  much  as  16-89  per  cent, 
nitrogen,  and  yields  a  considerable  amount  of  the  basic  derivatives 
on  hydrolysis.  It  is  therefore  classified  with  the  histones.  Haemo- 
globin yields  about  94  per  cent,  of  giobin  and  about  4'5  per  cent,  of 
the  chromogenic  group,  haematin. 

In  order  to  obtain  hcematin  in  a  pure  condition  it  is  usual  to  start 
with  the  crystalline  derivative  of  haemoglobin  known  as  hcemin. 
When  some  dried  blood  is  heated  with  a  crystal  of  common  salt  and 
placed  in  acetic  acid  on  a  slide,  a  residue  is  obtained  in  which  a  number 
of  reddish-brown  needles  are  embedded  known  as  Teichmann's  crystals 
or  haemin  crystals  (Fig.  358).  The  preparation  of  these  crystals  is  often 
used  as  a  convenient  test  for  the  identification  of  blood. 

In  order  to  obtain  them  in  large  quantities  the  following  method,  devised 
by  Chalfejew,  is  employed.  One  volume  of  dcfibrinated  blood  is  added  to  four 
volumes  of  glacial  acetic  acid  previously  heated  to  80°  C.     As  soon  as  the 

*  When  the  change  is  effected  by  reducing  agents  we  must  assume  that  the 
oxygen  of  the  water  or  air  is  the  source  of  that  required  for  the  oxidation  of  the 
reduced  haemoglobin  to  methaemoglobin. 


THE  RED  BLOOD-CORPUSCLES  9.'33 

temperature  hass  fallen  to  60°  C.  the  liquid  is  again  warmed,  and  then  allowed 
to  cool.  Crystals  are  formed  which  arc  allowed  to  stand  for  twelve  hours  and 
are  then  separated  and  washed  by  decantation,  first  with  distilled  water  and 
then  with  graduated  strengths  of  alcohol.  In  order  to  purify  these  crystals 
the  crude  material  is  shaken  for  fifteen  minutes  with  a  mixtiu-e  of  chloroform 
and  pyridine.  The  solution  is  filtered  and  then  th^o^v^^  into  glacial  acetic  acid 
previously  saturated  with  sodium  chloride  and  heated  to  105°  C.  A  few  drops 
of  concentrated  hydrochloric  acid  are  then  added  and  the  mixture  allowed  to 
stand  for  twenty-four  hours.  Tlie  crystals  which  separate  out  are  filtered  off, 
washed  with  dilute  acetic  acid,  and  then  dried. 

HsBmin  crystals  have  been  regarded  as  hydrochloride  of  hsematin. 
Elementary  analysis  shows  that  they  have  the  following  formula 
(Kiister):    C34H3304N'4Cl.Fe.      By    dis- 
solving hsemin  in  alkalies  and  throwing  -^        '^■L-\^:^^ 
the  solution  into  an  excess   of   acid  a           J^l    t 
precipitate  is  obtained  which  is  haematin.       , ,  J  ^f  "    %  ^^  %^  '  \ 
Ha)niatin  forms  a  brown  powder  of  bluish-     ''^   ^  -^^^s,^  \        ^  "^   4 
black  colour  and  metallic  lustre.     It  is     f     ^'^      ,     n?     **»        Ww\K 
insoluble  in  water,  alcohol,  or  ether,  but     -^    ;l    ^         "^  .      v-j.* 
is  slightly  soluble   in  glacial  acetic  acid    /         '  ^^1     '•    ^y 
and   in   absolute   alcohol.      It  is  easily    ^ru'-^''"    «k^       ■^r»'      \'ji' 
soluble  in  concentrated  sulphuric  acid,       tc^-'^-H    W"  k     ^ 
but  undergoes  decomposition,  losing  its          '"/^^     i.  J^         ,;=^ 
atom  of  iron  and  being  transformed  into  "L 
hremato porphyrin,   which   forms   a  deep       Fru.  358.    Hamin  crystals, 
purple  solution.  The  formula  of  hsematin 

has  not  yet  been  ascertained  with  certainty.  It  is  either  CajHgjNjO^Fe 
or  C34H32N405Fe.  Its  compounds  with  acids  and  alkalies  are 
spoken  of  as  acid  and  alkaline  hsematin,  and  each  gives  a  charac- 
teristic absorption  spectrum  (Fig.  359).  The  alkaline  solutions  exhibit 
one  indistinct  absorption  band  between  C  and  D,  the  acid  solutions 
an  absorption  band  also  between  C  and  D  but  nearer  to  C,  and 
resembling  somewhat  the  band  presented  by  metha9moglobin.  Accord- 
ing to  Hoppe-Seyler  and  Gamgee  perfectly  pure  solutions  of  ba3matin 
in  alkalies  are  quite  unaffected  by  reducing  agents  ;  in  the  presence  of 
certain  foreign  matters,  however,  alkaline  heematin,  when  treated 
with  reducing  agents,  exhibits  a  spectrum  known  as  that  of  reduced 
alkaline  ha^matin,  which  is  practically  identical  with  that  of 
ha9niochromogen.  The  same  change  is  further  observed  when  alkaline 
hromatin  made  by  the  action  of  alkaUes  on  ordinary  blood  is  treated 
with  reducing  agents  such  as  ammonium  sulphide.  Since  this  sub- 
stance hsemochromogen  is  responsible  for  the  respiratory  functions  of 
the  haemoglobin,  i.e.  the  power  of  its  molecule  to  iorm  unstable  com- 
pounds with  oxygen,  its  preparation  merits  fuller  consideration. 

Hcemochromogen  is  prepared  by  the  action  of  caustic  alkalies  on 


93i  PHYSIOLOGY 

haemoglobin  in  the  absence  of  oxygen.  For  this  purpose  a  test-tube 
containing  a  solution  of  sodium  or  potassium  hydrate  is  placed  in  a 
bottle  with  two  necks  containing  a  solution  of  haemoglobin,  care  being 
taken  not  to  spill  any  of  the  alkaline  solution.  Hydrogen  is  then  passed 
through  the  larger  bottle  until  the  haemoglobin  is  entirely  reduced  and 
all  the  air  is  replaced  by  hydrogen.  The  bottle  is  then  inverted  so  as  to 


Fig.    3.59.     Absorption  spectra  of  hsemoglobin  and  its  derivatives. 

1.  Oxyhsemoglobin.  2.  Reduced  lipemoglobin.  3.  Metha;moglobin. 
4.  Alkaline  methsemoglobin.  5.  Acid  hseraatin  in  ether  (i.  Alkaline 
hffimatin  in  rectified  spirit.  7.  Reduced  haematin.  8.  Acid  hsematopor- 
phyrin.     9.  Alkaline  liaematoporphyrin.     (From  MacMunn.) 


mix  its  contents  with  the  caustic  alkali,  when  hoemochromogen  is  formed 
and  can  be  recognised  by  its  characteristic  colour  and  spectrum.  The 
haemochromogen  in  solution  has  a  cherry-red  colour,  and  when 
sufficiently  diluted  shows  two  well-marked  absorption  bands  identical 
with  those  given  by  reduced  alkaline  haematin  (Fig.  359,7).  Of  the  two 
absorption  bands  which  are  situated  between  D  and  E,  that  nearest  to 
D  has  very  sharply  defined  borders  ;  the  position  of  the  two  absorption 
bands  may  be  given  in  terms  of  their  wave-lengths  as  follows  :  X  567  to 
547  and  X  532  to  518.  The  band  nearest  D  is  given  by  haemochromogen 


THE  RED  BLOOD-CORPUSCLES  935 

solutions  diluted  so  that  there  is  only  one  part  of  the  pij^nient  in 
25.000  parts  of  water,  so  that  the  formation  of  reduced  alkaline 
hasmatin  is  an  even  more  delicate  test  for  blood  than  the  spectrum  of 
oxyhaemoglobin  itself.  When  CO-haemoglobin  is  treated  in  the  same 
way  with  alkali  in  the  absence  of  oxygen,  a  body  C0-ha3mochromogen 
is  formed  which  contains  exactly  the  same  volume  of  CO  in  combina- 
tion as  the  original  CO-hsemoglobin.  This  fact,  combined  with  the 
possibility  of  reducing  ordinary  alkaline  haematin  by  the  action  of 
ammonium  sulphide  or  Stokes's  fluid,  indicates  that  the  group  of 
atoms  which  in  haemoglobin  is  responsible  for  taking  up  oxygen  or 
carbon  monoxide  gas  passes  unchanged  into  the  haemochromogen 
molecule.  Haemochromogen  therefore  represents  an  iron-containing 
coloured  radical  which  can  combine  with  protein  bodies  to  form 
haemoglobin,  and  is  responsible  for  the  oxygen-combining  powers  of 
the  latter.  We  may  assume  therefore  that  oxyhaemoglobin  and 
CO-haemoglobin  contain  oxyhaemochromogen  and  CO-haemochromogen 
respectively. 

H.CBmaioporph>jrin.  If  haemoglobin,  haematin,  or  haemin  be  mixed 
with  concentrated  sulphuric  acid,  it  dissolves  forming  a  purple-red 
solution.  On  pouring  this  solution  into  a  large  quantity  of  water, 
haematoporphyrin  is  thrown  down  in  the  form  of  a  brown  precipitate. 
In  order  to  prepare  haematoporphyrin,  pure  crystallised  haemin  is  added 
to  a  saturated  solution  of  hydrobromic  acid  in  glacial  acetic  acid.  The 
whole  is  allowed  to  stand  for  three  or  four  days  and  then  thrown  dowTi 
into  distilled  water.  The  resulting  mixture  is  filtered  and  the  haemato- 
porphyrin thrown  down  by  careful  neutralisation  of  the  hydrobromic 
acid  with  caustic  soda.  Haematoporph}Tin  is  easily  soluble  in  alkalies 
and  somewhat  less  readily  so  in  acids,  forming  alkahne  and  acid 
haematoporphyrin  respectively.  The  formula  of  haematoporphyrin  has 
been  given  by  Nencki  and  Sieber  as  CigHigNoOg,  and  is  according  to 
them  isomeric  with  the  chief  bile-pigment,  bihrubin.  According  to 
Zaleski  its  formula  is  C34H38N4O6  =  2C17H19N2O3.  An  alcoholic 
solution  of  haematoporphyrin  acidulated  with  hydrochloric  acid  shows 
two  absorption  bands  :  one,  the  fainter,  between  C  and  D.  and  the 
other,  broader  and  more  defined,  midway  between  D  and  E.  Solutions 
of  alkaline  haematoporphyrin  show  four  absorption  bands  :  a  weak 
band  between  C  and  D.  another  between  D  and  E,  a  more  strongly 
marked  band  nearer  to  E,  and  a  fourth  band,  darkest  of  all.  between 
band  F.  tt  will  be  observed  that  in  the  formation  of  ha^natoporphyrin 
from  htematin  the  iron  of  the  latter  has  been  spHt  off  by  the  action  of 
the  strong  acid.  Laidlaw  has  found  that  the  spHtting  off  of  iron  occurs 
much  more  readily  in  the  absence  of  oxygen.  If  reduced  haemoglobin 
be  taken,  or  defibrinated  blood  which  has  been  allowed  to  stand  until 
it  is  thoroughly  reduced,  it  is  sufficient  to  add  15  per  cent,  hydrochloric 


936  PBYSIOLOGY 

acid  in  order  not  only  to  convert  the  greater  part  of  the  haemoglobin  to 
hsBmatin  but  to  spUt  off  the  iron  of  the  latter  and  form  hsemato- 
porph}Tin.  Haematoporphrrin  occurs  in  minute  quantities  in  normal 
urine  and  in  larger  quantities  in  certain  toxic  conditions,  especially  in 
poisoning  by  sulphonal,  when  the  urine  may  have  a  bright  purple 
colour.  It  is  important  to  remember  that  although  urine  is  acid 
from  the  presence  of  acid  sodium  phosphate,  urinary  haemato- 
porphvrin  is  always  alkaline  hsematoporphyrin  and  gives  the  spectrum 
of  this  body. 

CHEMICAL  RELATIONSHIPS  OF  HiCMATIN.  Hjematin,  or  the  reduced 
hfemocliromogen,  is  widely  diffused  tlirough  the  animal  kingdom,  occiuring  in 
the  form  of  hsemoglobin  in  a  large  number  of  the  invertebrata,  as  well  asin  all 
the  vertebrata  except,  perhaps,  Amphioxus.  Since  the  respiratory  function  of 
haemoglobin  depends  on  the  power  of  its  iron-containing  radical  to  combine  with 
a  molecule  of  oxygen,  formmg  an  easily  dissociable  compound,  it  becomes  of 
interest  to  trj-  whether  by  a  study  of  its  disintegration  products  we  can  throw 
any  light  on  its  chemical  relationships  and  on  the  conditions  of  its  formation  in 
the  living  organism.  When  hsematin  is  oxidised  -n-ith  sodium  bichromate  and 
acetic  acid  two  new  acids  are  formed,  called  the  haematinic  acids.  One  of  these 
has  the  formula  CgHgOiX,  and  the  other  CgHgOa.  The  first  acid  is  converted 
into  the  second  by  the  action  of  alkalies.  The  relationship  of  the  two  haematinic 
acids  can  be  represented  by  the  following  formxilse  : — 

/CO.  /C0\ 

C5H7<  )0  C5H7        NH 

^co/  \co/ 

COOH  COOH 

If.  on  the  other  hand,  haemin  or  hsematoporphxTUi  be  reduced  by  the  action  of 
hydriodic  acid  dissolved  in  acetic  acid  with  the  addition  of  phosphonium  iodide, 
and  the  product  be  distilled  with  steam,  a  substance  is  obtained  in  the  distillate 
which  is  haemopjTrol,  and  has  the  formula  CgHigN.  HaemopjTrol  readily 
oxidises  to  a  red  substance  on  exposure  to  the  air.  If  ammonia  be  added  to  the 
coloured  solution  the  colour  changes  to  yellow,  which,  on  the  addition  of  an 
ammoniacal  solution  of  zinc  chloride,  changes  to  pink  with  a  green  fluorescence. 
These  reactions  aie  also  given  by  ui'obilin,  one  of  the  urinary  pigments  and  the 
chief  pigment  of  Ihe  faeces,  as  well  as  by  hydrobilirubin,  a  substance  obtained 
by  the  action  of  tin  and  sulphuric  acid  on  an  alcoholic  solution  of  haematin. 
Haemop\Trol  has  been  shown  by  Nencki  and  Zaleski  to  have  the  formula  : 

H3  C — C C — C3  H  7 

II         II 
HC        CH 

\/ 
NH 

i.e.  it  is  methyl  propylpyrrol. 

The  same  substance,  haemopj-rrol,  can  be  obtained  from  chlorophj'll,  the  green 
colouring-matter  of  plants.  Chlorophyll,  on  treatment  with  strong  acid,  is 
converted  into  phyllocyanin,  and  then  into  phyllothaonin.  The  latter,  on 
treatment  with  alcoholic  caustic  soda  in  sealed  tubes  at  190°  C,  yields  a  sub- 
stance called  phylloporphjTin,  which  has  a  purple  colour  and  gives  an  absorption 
spectrum  similar  to  that  of  haematoporphjTin.  The  close  relationship  of  the 
two  is  showTi  bv  their  formulae  : 


THE  RED  BLOOD-CORPUSCLES  937 

HsematoporphjTin,  CgiHagOeN^. 
Phylloporphyrin,  C34H38O2N4. 

Phyllocyaniu  or  pliylloporphyrin,  like  the  corresponding  blood  pigment,  yields 
haemopyrrol  on  treatment  with  hydriodic  acid  and  phosphonium  iodide.  Thus 
the  same  group  forms  the  basis  both  of  the  substance  which  is  responsible  in  the 
plant  for  the  assimilation  of  carbon  from  carbon  dioxide,  and  of  the  pigment 
which  in  the  animal  is  the  carrier  of  oxygen  between  the  tissues  and  the  surround- 
ing medium.  Nencki  and  Zaleski  suggest  that  each  molecule  of  hsematopor- 
phyrin  is  built  up  out  of  four  molecules  of  hajmopjTrol,  and  give  the  following 
as  the  possible  structural  formula  of  htemin  : 

CH3.C— C.CH  :  C  (OH).C  :  C.CH  :  CH.C  — C.CH3 

II  11  II  II        II 

HC        CH  O    FeCl        HC       CH 

\/  \/ 

NH  NH 

CH3C— C.CH  :  C  (OH).C  :  C.CH  :  CH.C— C.CH3 

II  II  II  II 

HC        CH  HC        CH 

\/  \/ 

NH  NH 

THE  SYNTHESIS  OF  THE  BLOOD-PIGMENTS.  Chemists  have  not 
yet  succeeded  in  the  artificial  formation  of  ha3matoporph}Tin,  although 
it  is  probable  that  the  artificial  formation  of  haemopyrrol  will  be 
effected  at  no  distant  date.  Given  hsematoporphyrin,  however, 
evidence  has  been  brought  forward  both  by  Menzies  and  Laidlaw  of 
the  possibiUty  of  forming  artificially  both  hsematin  and  haemoglobin, 
or  some  substance  indistinguishable  from  the  latter. 

Reduced  haemoglobin  is  a  compound  of  haemochroraogen  and  a 
protein,  globin.  The  splitting  off  of  the  prosthetic  chromatogenic 
group — hsemochromogen — can  be  effected  either  by  acid  or  alkali. 
When  the  latter  is  employed  we  obtain  a  red  solution  which  is  fairly 
stable,  and  can  be  converted  by  shaking  up  with  air  into  ordinary 
alkaline  haematin.  With  acids  the  decomposition  is  easily  carried 
further.  Even  with  2  per  cent,  hydrochloric  acid  a  certain  amount  of 
haematoporphyrin  is  formed,  and  if  the  strength  of  the  acid  be  increased 
to  L5  per  cent,  the  whole  of  the  iron  is  split  off  and  the  haemo- 
chromogen  is  converted  entirely  into  haematoporphyrin. 

If  oxy haemoglobin  be  treated  in  the  same  way  it  yields  acid  or 
alkaline  haematin  directly,  so  that  haematin  must  be  regarded  as 
an  oxyhoemochromogen.  The  distinction  drawn  by  Hoppe-Seyler 
between  haemochromogen  and  reduced  alkaUne  ha3matin  had  its  chief 
ground  in  the  fact  that  pure  haematin  is  not  reduced  to  haemochromogen 
by  the  action  of  such  reducing  agents  as  ammoniimi  sulphide.  The 
conversion  can,  however,  be  easily  effected  by  using  a  strong  reducing 
agent,  such  as  hydrazine  hydrate.  Whether  the  hfDmatin  contains 
the  whole  of  the  oxygen  of  the  oxyhaemoglobin  is  doubtful.     According 


938  PHYSIOLOGY 

to  Ham  and  Balean,  when  oxyhaemoglobin  is  converted  by  means  of 
acids  into  acid  hsematin,  exactly  half  of  the  oxygen  of  the  oxyhsemo- 
globin  is  given  off,  so  that  haematin  would  only  contain  one-half  of  the 
oxygen  of  the  oxyhaemoglobin.  There  is  a  marked  difference  betw^een 
the  stability  of  hsematin  and  haemochromogen.  In  the  oxidised  form 
of  hsematin  the  iron  is  firmly  bound  and  can  only  be  split  off  by  using 
strong  sulphuric  acid,  concentrated  hydrochloric  acid  being  insufficient 
for  the  purpose. 

Since  pure  haemochromogen  is  readily  converted  quantitatively 
into  haematoporphyrin,  it  seems  to  consist  of  a  simple  compound  of 
haematoporphyrin  and  iron  in  the  ferrous  condition.  It  has  been  shown 
by  Laidlaw  that  the  change  in  the  reverse  direction,  i.e.  the  combina- 
ton  of  iron  with  haematoporphyrin  to  form  haemochromogen,  may  be 
effected  with  equal  ease.  One  gramme  haematoporphyrin  prepared  by 
Nencki's  method  is  dissolved  in  dilute  ammonia  and  warmed  in  a  flask  on 
the  water-bath.  Some  Stokes's  fluid,  prepared  from  about  2  grm.  ferrous 
sulphate,  and  a  few  drops  of  a  50  per  cent,  hydrazine  hydrate  solution 
are  added.  At  the  end  of  one  or  two  hours  the  solution  is  seen  to  be  of  a 
bright  red  colour  when  examined  in  thin  layers,  and  on  dilution  shows 
the  typical  absorption  spectrum  of  haemochromogen,  which  changes 
to  that  of  alkaUne  haematin  on  shaking  with  air.  Strong  potash  is 
added,  and  the  ammonia  is  boiled  off  in  an  evaporating  dish  with 
free  exposure  to  the  air.  The  hydrazine  is  decomposed,  and  a  solution 
of  haematin  remains,  and  can  be  precipitated  by  acidification  with 
hydrochloric  acid.  The  pigment  obtained  in  this  way  agrees  in  every 
respect  with  that  prepared  from  oxyhaemoglobin.  Analysis  of  the 
product  gave  9-58  per  cent,  of  iron,  which  agrees  with  Nencki's  formula 
for  haematin,  C32H3oN403Fe.  The  ease  with  which  this  combination 
is  effected  suggests  that  haematin  consists  of  two  haematoporphyrin 
groups  united  by  means  of  iron. 

A  pigment  occurring  in  the  wing  feathers  of  certain  birds,  called  turacin, 
was  sho^\^l  by  Church  to  contain  copper,  and  to  yield,  on  treatment  with  strong 
sulphuric  acid,  a  substance  indistinguishable  from  haematoporphyrin.  Laidlaw 
has  succeeded  in  sjTithetising  this  pigment  by  treating  ordinary  hsemato- 
porphjTin  obtained  from  blood  with  ammoniacal  copper  solution,  showing  that 
it  is  a  compound  corresponding  to  hsematin,  in  which  the  place  of  iron  is  taken 
by  copper.  ^ 

It  was  stated  some  years  ago  by  Menzies  that  a  solution  of  impure 
haemochromogen,  prepared  by  the  action  of  ammonium  sulphide  or 
alkahne  haematin  obtained  in  the  ordinary  way  from  blood, on  standing 
for  some  days  was  reconverted  into  reduced  haemoglobin.  Ham  and 
Balean  have  confirmed  this  observation,  and  have  shown  in  addition 
that  haemochromogen,  prepared  by  the  action  of  ammonium  sulphide  on 
an  alkahne  solution  of  pure  haemin,  though  perfectly  stable  by  itself, 


THE  RED  BLOOD-CORPrSCLES  939 

was  rapidly  reconverted  into  haemoj^jlobin  if  a  solution  of  globin  were 
added  to  the  mixture.  The  same  chan<.'e  took  place  if  eg^-white  were 
used  instead  of  globin.  The  haemoglobin  thus  formed  was  changed  int(>v 
oxyhsemoglobin  on  shaking  with  air.  Although  in  these  experiments  the 
oxyhaemoglobin  was  not  separated  in  the  crystalline  form,  its  colour 
and  spectral  characters  are  so  very  distinctive  that  we  are  justified 
in  concluding  not  only  that  it  is  possible  to  effect  a  recombination  of 
the  haemochromogen  and  globin.  but  also  that  other  proteins  can  take 
the  place  of  globin  in  the  haemoglobin  molecule. 


THE   LIFE-HISTORY  OF   THE   RED   BLOOD-CORPUSCLES 

The  growth  of  the  embryo  as  well  as  of  the  young  animal  must  be 
attended  with  a  continual  increase  in  the  number  of  red  blood- 
corpuscles  present  in  the  body.  In  the  developing  embryo  the  first 
formation  of  red  corpuscles  occurs  in  the  vascular  area.  In  the  chick, 
about  the  twentieth  hour  of  incubation,  the  area  opaca,  which  sur- 
rounds the  blastoderm,  and  will  later  become  the  area  vasculosa, 
presents  on  examination  under  the  low  power  a  network  of  anasto- 
mising  strands  more  opaque  than  the  rest  of  the  area.  On  section 
these  strands  are  seen  to  be  made  up  of  cellular  masses,  the  ordinary 
mesenchyma,  with  branched  cells  and  amoeboid  corpuscles  lying 
between.  The  cells  in  these  cords  are  continually  multiplying  by 
indirect  division.  Those  on  the  outer  side  of  the  cord  become  the 
endothelium  of  dilated  blood-vessels,  while  those  in  the  interior  acquire 
a  yellowish  colour  from  the  laying  down  of  haemoglobin  in  their 
cytoplasm.  The  cords  become  canahsed.  and.  as  soon  as  a  connection 
is  established  with  the  vascular  system  of  the  embryo,  the  newly 
formed  blood-corpuscles  move  slowly  on  into  the  general  circulation. 
The  red  corpuscles  in  the  bird  are  true  erythrocytes,  i.e.  are  nucleated 
cells.  The  leucocytes  seem  to  arise  by  the  immigration  of  wandering 
cells  from  the  surrounding  mesenchyma.  Other  places  in  the  foetus 
where  a  similar  growth  of  corpuscles  proceeds  throughout  fcEtal  life 
are  the  liver  and  the  spleen,  and  later  on  the  bone-marrow. 

In  the  mammal  the  nucleated  erythrocj'tes,  though  forming  the 
majority  of  the  red  corpuscles  in  early  foetal  life,  become  fewer  and 
fewer  in  number  as  gestation  advances,  so  that  at  birth  practically  the 
whole  of  the  corpuscles  are  of  the  non-nucleated  type.  These,  how- 
ever, can  be  shown  to  be  derived  from  nucleated  red  corpuscles  by  a 
process  either  of  extrusion  or  of  degeneration  and  solution  of  the 
nucleus  (Fig.  360).  The  formation  of  red  corpuscles  does  not  cease  with 
the  end  of  foetal  life  or  even  with  the  attainment  of  full  stature  by  the 
animal.  We  have  definite  proof  that  a  continual  formation  of  red 
corpuscles  can  proceed  and  is  proceeding  throughout  the  whole  of 


y40  PHYSIOLOGY 

adult  life.  In  an  adult  the  total  volume  of  blood  and  the  total  number 
of  corpuscles  remain  approximately  constant.  By  bleeding  an  animal 
we  can  diminish  the  total  amount  of  corpuscles.  The  first  effect  of 
such  a  bleeding  is  that  the  fluid  parts  of  the  blood  are  made  up,  so 
that  the  volume  of  the  blood  is  restored  to  normal  and  the  blood 
therefore  becomes  relatively  poor  in  corpuscles.     In  a  few  weeks, 


Fig.  36l>,     Part  of  a  blood-vessel  from  the  yolk-sac   of  the  rabbit  embryo, 

showing  the   changes  which  occur  in  the  formation  of  erythrocytes. 

(From  ScHAFER  after  Maximow  ) 

a,   megaloblasts  ;   h,  normoblasts    changing    into  erythroblasts  ;  c,  ery- 

throblasts,    in    which    the    nuclei    are    disappearing ;    d,    an    erythrocyte 

fully    formed,  but  not  yet  disc-shaped  ;  en,   phagocytic  endothelial  cells  ; 

I,  lymphocytes ;    k,    a  divided  lymphocyte ;    n,   erythroblasts,    shrunken 

with  atrophic  nucleus. 


however,  the  corpuscular  content  of  the  blood  is  found  to  be  once 
more  normal,  showing  that  the  loss  of  corpuscles  has  been  followed  by 
a  compensatory  regeneration.  The  fact  that  the  pigments  constantly 
leaving  the  body  with  the  urine  and  faeces,  namely,  urochrome  and 
urobilin  or  stercobihn,  are  derived  by  means  of  the  liver  from  haemo- 
globin, shows  that  a  constant  destruction  of  red  corpuscles  must  be 
proceeding.  Since  the  number  of  corpuscles  remains  unaltered,  this 
loss  of  haemoglobin  must  be  made  good  by  a  continual  regeneration  of 


THE  RED  BLOOD-CORPUSCLES  941 

fresh  haemoglobin  and  new  red  corpuscles.  The  seat  of  the  formation 
of  red  corpuscles  in  the  higher  vertebrates  is  the^bone-marrow.  Here 
we  have  a  structure  protected  from  pressure  where  the  capillaries  and 
veins  are  dilated  and  thin-walled,  and  allow  a  slow  passage  of  blood 
and  the  entry  of  newly  formed  corpuscles  through  the  imperfect  waUs 
into  the  blood-stream  (Fig.  361).  That  the  marrow  is  the  tissue  involved 
in  the  process  is  shown  by  the  fact  that  it  is  the  only  tissue  of  the  body 
which  undergoes  an  alteration  in  appearance  when  blood  formation  is 


^'^  i^^'T'^^ 


-'*'©€': 


,,..J-A^'-i''^'-^'-'^ 


y  ■--'^'L  m! ^^j^-- "w ^    r^: 


S^f^ 


Fig.  361.     Section  of  red  marrow  of  mammal.     (Bohm  and  Davidoff.) 

a,  e,  erythro blasts  ;   6,  reticulum;   c,  myeloplax  ;   d,  g,  marrow  cells  ; 

/,  a  marrow  cell  dividing  ;   h,  a  space  which  was  occupied  by  fat. 

stimulated  by  such  means  as  repeated  bleeding  or  destruction  of 
corpuscles  by  the  injection  of  toxic  agents.  Under  such  conditions 
the  red  marrow,  which  in  adult  mammals  is  present  only  in  the 
epiphyses,  is  found  to  have  increased  in  extent  and  in  many  cases  to 
occupy  the  greater  part  of  the  shaft  of  the  bone,  having  taken  the 
place  of  the  yellow  marrow.  It  is  in  the  red  marrow  therefore  that 
we  must  seek  the  precursors  of  the  red  blood-corpuscles.  In  the  bird 
the  erythroblasts,  i.e.  the  precursors  of  the  red  blood-corpuscles,  form 
a  sort  of  inner  lining  to  the  dilated  capillaries  of  the  marrow  (Fig.  362). 
Here  we  can  see  all  grades  between  the  colourless  nucleated  corpuscle 
which  lies  nearest  the  periphery  and  the  fully  formed  red  oval  corpuscle 
containing  ha3moglobin,  lying  next  the  lumen  and  ready  to  be  carried 
away  in  the  blood  stream.  If  blood  formation  has  been  stimulated 
by  repeated  bleeding,  this  blood-forming  tissue  is  found  to  occupy  the 
greater  part  of  the  lumen  of  the  marrow  capillaries.  If,  however, 
blood  formation  has  been  reduced  to  its  lowest  extent  by  a  process  of 
chronic  starvation,  the  erythroblasts  form  a  single  layer  of  cells  just 


942 


PHYSIOLOGY 


inside  the  dilated  capillaries  and  intermediate  stages  between  the 
er\i;hroblasts,  and  the  fully  formed  erythrocytes  are  almost  entirely 
wanting.  In  the  frog  this  process  of  blood-corpuscle  formation  occurs 
only  at  one  period  of  the  year,  namely,  in  the  early  summer,  and  it  is 
only  at  this  time  that  the  bones  are  found  to  contain  red  marrow.  In 
mammals  the  process  is  very  similar.  In  the  red  marrow  are  a  number 
of  nucleated  cells  containing  haemoglobin,  which  are  thought  by 
Lowit  to  be  themselves  derived  trom  colourless  nucleated  cells.  In 
the  confused  medley  of  colourless  cells  which  exists  in  the  bone- 
marrow  and  are  precursors  of  all  the  varied  corpuscles  found  in  the 


vrv.\v 


Fig.  362.     Section  of  red  marrow  of  pigeon.     (Denys.) 

Ic,  eosinophile  leucocytes  ;  eg,  fat  cells  ;  e,  nucleus  of  endothelial 
cell  of  blood-vessel ;  ca.  blood-capillary ;  er,  erythroblasts  lying 
within  vascular  endothelium  ;   glr,  fully  formed  red  corpuscles. 


blood,  it  is  difficult  to  be  certain  of  the  identity  of  the  colourless 
erythroblasts  and  to  distinguish  them  from  the  smaller  colourless 
cells  engaged  in  bone  formation  or  in  the  production  of  leucocytes. 
The  hsemoglobin-containing  cells  are  often  to  be  seen  in  process  of 
division,  and  the  nucleated  daughter-cells  appear  to  undergo  a  process 
of  nucleolysis,  the  nucleus  being  extruded  or  dissolved.  When  blood 
formation  is  quickened  as  the  result  of  previous  destruction  or  loss, 
some  of  these  immature  nucleated  blood-discs  may  make  their  way 
into  the  circulation  and  be  found  in  the  blood,  where  they  are  spoken 
of  as  normoblasts. 

How  long  a  corpuscle  continues  to  exist  in  ths  circulating  blood  is 

not  known.     The  experiments  made  to  determine  the  length  of  time 

during  which  foreign  corpuscles  such  as  those  of  birds  can  be  recognised 

after  injection  into  the  circulation  of  a  inammal  are  evidently  beside 

he  mark,  since  these  foreign  cells  will  be  destroyed  by  the  serum  and 


THE  RED  BLOOD-CORPUSCLES  943 

rapidly  taken  up  by  the  phagocytes  of  the  body.  Sooner  or  later,  how- 
ever, every  corpuscle  undergoes  disintegration,  a  process  which  is 
generally  ushered  in  by  the  ingestion  of  the  corpuscle  by  some  phago- 
cytic cell.  Thus  in  the  hamolyniph-glands  and  in  the  spleen  we  find 
large  cells  which  have  englobed  red  corpuscles  and  in  which  we  can 
recognise  pigment-granules  obtained  from  their  destruction.  The 
chief  place  of  disintegration  of  the  hajmoglobin  is  certainly  the 
liver,  i.e.  the  organ  where  the  haematin  is  converted  into  bile- 
pigment.  Lijection  pf  haemoglobin  into  the  circulation  causes 
increased  secretion  of  bile-pigment.  A  section  of  normal  liver  im- 
mersed in  potassium  ferrocyanide  and  then  in  acid  alcohol  shows  the 
presence  of  iron  by  the  assumption  of  a  blue  colour.  The  amount  of 
iron  which  can  be  demonstrated  in  the  liver  in  this  way  is  enormously 
increased  by  any  condition  which  augments  the  rate  of  blood  destruc- 
tion. In  the  pathological  condition  known  as  pernicious  anaemia,  as 
well  as  after  poisoning  by  the  injection  of  pyrogallic  acid  or  toluylene 
diamine,  both  of  which  agents  cause  a  great  destruction  of  red  blood- 
corpuscles,  the  liver  on  treatment  in  this  way  assumes  a  deep  blue 
colour.  In  some  cases  crystals  of  haemoglobin  have  been  seen  within 
the  nucleus  of  the  liver-cell.  In  the  destruction  of  the  corpuscles  the 
haemoglobin  is  dissociated  first  into  its  protein  and  chromogenic 
moieties  ;  the  haemochromogen  then  loses  its  iron  and  is  converted 
into  bile-pigment.  The  iron  remains  in  the  liver  and  is  probably 
retained  in  the  body  and  utilised  for  the  formation  of  the  fresh  haemo- 
globin necessary  for  the  newly  forming  red  blood-corpuscles  in  the 
bone-marrow. 


SECTION  III 

THE   BLOOD-PLATELETS 

The  very  existence  of  these,  the  third  class  of  formed  elements  of 
the  blood,  is  still  a  matter  of  dispute.  If  a  drop  of  osmic  acid  be  placed 
on  the  finger,  which  is  then  pricked  through  the  drop  so  that  the  shed 
blood  may  mix  with  the  fixing  fluid  directly  it  leaves  the  vessels,  a 
drop  of  the  mixture  when  examined  under  high  powers  is  seen  to 
present  a  number  of  granular  bodies  from  one-third  to  one-half  the 
diameter  of  a  red  blood-corpuscle.  Their  number  has  been  variously 
stated  from  180,000  to  800,000  per  cubic  milhmetre,  so  that  they 
rank  second  in  point  of  number  among  the  morphological  constituents 
of  the  blood.     Their  shape  varies  considerably.     Some  are  bi-convex 


Fig.  363.  Blood-platelets,  highly  magnified,  showing  the  amoeboid 
forms  which  they  assume  when  examined  under  suitable  con- 
ditions, and  also  exhibiting  the  chromatic  particle  which  each 
platelet  contains,  and  which  has  been  regarded  as  a  nucleus. 
(After  KoPSCH.) 

structures  ;  others  are  flatter  with  numerous  processes.  They  may  be 
isolated  or  agglutinated  into  clumps.  Their  shape,  size,  and  number 
vary  according  to  the  fluid  with  which  the  blood  is  mixed  or  the  method 
adopted  for  their  demonstration.  When  blood  is  examined  in 
Hayem's  fluid  *  nearly  all  the  blood-platelets  appear  as  bi-convex  discs. 
The  best  method  for  the  display  of  platelets  is  apparently  that  given 

*  Hayem's  fluid  is  made  up  as  follows  : 

Distilled  water 200  c.c. 

Sodium  chloride        ......  1  grm. 

Sodium  sulphate       ......  5  grm. 

Iodine  in  iodide  of  potassium     ....  3-5  c.c. 

944 


THE  BLOOD-PLATELETS  945 

by  Deetjen.  The  drop  of  blood  is  received  directly  from  the  vessels 
on  to  a  sheet  of  solid  agar  jelly  which  is  made  with  O-G  per  cent,  sodium 
chloride  solution  ^v^th  the  addition  of  sodium  metaphosphate  and 
bipotassium  phosphate.  When  examined  on  this  medium  large 
numbers  of  platelets  are  seen,  each  of  them  provided  with  numerous 
processes  (Fig.  363).  Their  central  part  is  more  strongly  refracting 
than  the  periphery  and  stains  with  basic  dyes,  so  that  it  has  been 
regarded  as  a  nucleus.  Similar  platelets  are  observed  when  the  blood 
is  received  into  normal  salt  solution,  and,  as  the  mixture  clots,  the 
filaments  of  fibrin  can  be  seen  often  to  radiate  from  a  disintegrated 
blood-plate  as  from  a  centre.  That  the  blood-platelets  are  concerned 
in  the  production  of  clots  is  shown  by  the  fact  that  in  the  living  vessels 
blood-platelets  aggregate  round  any  injured  spot  in  the  vessel  wall, 
and  later  fuse  together  so  as  to  form  an  adherent  thrombus  or  clot 


Fig.   364.     Blood-corpuscles  and  blood-platelets,  within  a  small  vein. 
(ScHAFEH  after  Osler.) 

which  covers  the  seat  of  injury  and  helps  to  repair  the  damage  and 
to  prevent  the  escape  of  the  contents  of  the  blood-vessel.  Blood- 
platelets  have  only  been  found  in  mammalian  blood  and  are  certainly 
absent  from  frogs'  blood  as  well  as  from  the  blood  of  fishes  and  birds, 
nor  can  they  be  demonstrated  in  any  of  the  serous  fluids  even  in 
mammals.  Certain  nucleated  spindle-shaped  cells  have  been  described 
in  frogs'  blood  as  blood-platelets,  but  these  are  probably  immature 
red  blood-corpuscles  and  not  homologous  with  the  blood-platelets  of 
mammals.  (Blood-platelets  themselves  were  regarded  by  Hayem  as 
stages  in  the  formation  of  red  blood-corpuscles.)  If  the  blood  of  an 
animal  be  defibrinated  by  bleeding,  continually  whipping  the  blood 
and  returning  it  to  the  veins  of  the  animal,  it  wiU  be  found  for  the 
next  few  days  to  be  quite  free  from  blood-platelets.  There  is  no  doubt 
therefore  that  it  is  possible  by  the  most  varied  means  to  demonstrate 
the  existence  of  blood-platelets  in  shed  blood.  According  to  the 
method  adopted,  so  do  the  number  and  form  of  these  platelets  vary. 
Moreover  they  can  be  seen  to  be  deposited  from  the  circulating  blood 
in  the  living  animal  on  any  injured  portion  of  the  vessel  wall  or  on 
any  foreign  body  introduced  into  the  blood-current  (Fig.  304).  On  the 
other  hand,  it  is  possible  to  obtain  blood  in  an  uncoagulated  state  from 
the  vessels  in  which  no  trace  of  platelets  is  to  be  observed.  As  Buck- 
master  has  shown,  a  film  of  blood  examined  in  a  platinum  loop  and 
kept  carefully  at  the  temperature  of  the  body  presents  no  platelets  on 

60 


946  PHYSIOLOGY 

microscopic  examination  ;  and  the  same  absence  of  platelets  is  to  be 
noted  when  blood  is  received  into  sterile  blood-serum  of  the  same 
species  of  animal  and  kept  at  the  body  temperature.  On  allowing 
these  specimens  of  blood  to  cool,  blood-platelets  make  their  appear- 
ance. Many  specimens  of  non-coagulable  plasma,  such  as  peptone 
plasma  or  oxalate  plasma,  can  be  separated  by  means  of  the  centrifuge 
from  all  formed  elements.  If  the  plasma  be  cooled  to  0°  C. 
for  twenty-four  hours,  a  precipitate  indistinguishable  from  blood- 
platelets  is  found  to  have  been  produced  under  the  action  of 
cold.  We  are  therefore  probably  justified  in  concluding  that  the 
blood-platelets  do  not  form  a  constituent  of  normal  hving  blood,  but 
are  produced  in  the  plasma  either  on  contact  with  foreign  bodies  or 
lowering  of  its  temperature  from  37°  C.  to  18°  or  20°  C.  All  the 
various  fixing  fluids  which  have  been  recommended  for  the  display 
of  blood-platelets  owe  their  virtues,  not  to  the  fact  that  they  "preserve, 
but  to  the  fact  that  they  'produce  platelets.  These  may  therefore 
be  regarded  as  precipitates  produced  in  the  plasma  directly  it 
undergoes  alterations,  their  appearance  being  the  first  sign  of 
changes  in  this  fluid.  They  consist  of  some  substance  probably 
belonging  to  the  class  of  nucleo-proteins,  and  like  these  yield  a  precipi- 
tate on  gastric  digestion,  and  have  a  specific  affinity  for  basic  dyes. 
Even  after  their  first  appearance  they  are  unstable,  tending  to  undergo 
further  alteration  and  to  give  off  substances  to  the  surrounding  plasma 
which  play  an  important  part  in  the  formation  of  fibrin-ferment  and 
in  the  coagulation  of  the  blood. 


SECTION  IV 

THE  COAGULATION  OF  THE  BLOOD 

In  the  process  of  coagulation,  while  the  corpuscles  remain  to  a 
large  extent  intact,  the  plasma  becomes  solid  from  the  production  in 
it  of  a  network  of  fibrin,  being  converted  into  fibrin  j)lus  serum.  The 
question  of  coagulation  involves  the  consideration  of  the  precursors  of 
fibrin  and  of  the  conditions  which  determine  the  conversion  of  these 
precursors  into  fibrin.  It  is  evidently  impossible  to  arrive  at  any 
conclusions  on  these  points  during  the  few  minutes  which  elapse 
between  the  time  at  which  the  blood  leaves  the  vessels  and  the  appear- 
ance of  the  clot.  We  must  therefore  find  some  means  of  retarding 
coagulation  so  that  we  may  obtain  the  plasma  free  from  corpuscles 
and  be  able  to  initiate  coagulation  in  this  cell-free  fluid  at  will.  Having 
succeeded  in  staying  the  process  of  coagulation,  it  is  always  possible  to 
obtain  a  cell-free  plasma  either  by  allo\vdng  the  blood  to  settle  or,  better 
still,  by  the  employment  of  a  centrifugal  machine.  Under  the  influence 
of  centrifugal  force  the  corpuscles  are  thro^^^l  rapidly  down  to  the 
bottom  of  the  tube  and  the  clear  supernatant  plasma  can  be  syphoned 

£f 

METHODS  OF  PREVENTING  COAGULATION 

(1)  So  long  as  the  blood  is  in  contact  u-ith  the  uninjured  vessel  it  remains 
fluid.  If  the  jugular  vein  of  a  large  animal  such  as  the  horse  be  tied  in  two  places, 
the  blood  contained  between  the  hgatures  will  remain  fluid,  sometimes  for  days. 
If  the  tube  of  vein  be  hung  up,  the  corpuscles  sink  to  the  bottom  and  the  plasma 
in  the  upper  part  of  the  tube  can  be  poured  from  one  vein  to  another  Anthout 
undergoing  coagulation.  On  pouring  it  into  a  glass  vessel  or  bringing  it  in  contact 
"wiih  foreign  substances,  it  undergoes  coagulation. 

(2)  Wlien  an  incision  is  made  in  the  ordinary  way  into  a  blood-vessel  of  a 
bird  the  issuing  blood  clots  very  rapidly.  The  clotting  is  initiated  by  a  substance 
contained  in  the  tissues  surrounding  the  vessels.  If  therefore  the  vessel  be  isolated 
and  a  perfectly  clean  glass  cannula  be  inserted  into  it,  care  being  taken  not  to 
bring  the  cannula  in  contact  wth  any  of  the  surrounding  tissues,  blood  can  be 
dra\ni  off  into  a  sterihsed  beaker  perfectly  free  from  dust  and  will  remain  uncldttcd 
for  days.  Such  blood  can  be  centrifuged  and  the  cell-free  plasma  used  for  experi- 
ment. The  same  procedure  does  not  apply  to  the  mammal,  where  even  the  most 
scrupulous  care  to  prevent  contamination  by  the  tissue  juices  will  not  prevent 
the  blood  from  clotting  on  leaving  the  vessels. 

(3)  Clotting  can  be  excited  even  in  the  living  vein  by  introducing  into  the 
blood  any  solid  substance  which  is  wetted  by  the  blood.  If  the  contact  of  the 
blood  with  such  substances  be  prevented  by  receiving  it  into  vessels  previously 
coated  with  oil  or  with  paraffin  and  scrupulously  free  from  dust,  clotting  may 
often-  be  delayed  for  many  hours. 

947 


948  PHYSIOLOGY 

(4)  Cooled  plasma.  Horses'  blood  is  received  directly  into  a  narrow  vessel 
immersed  in  ice,  so  as  to  cool  it  rapidly  to  0°  C.  to  1°  C.  At  this  temperature  it 
remains  fluid  for  an  indefinite  time.  The  corpuscles  sink,  and  the  supernatant 
plasma  can  be  decanted  and  filtered. 

(5)  Methods  involving  Mixture  with  Neutral  Salts,  (a)  Magnesium  sulphate. 
Blood  from  any  animal  is  received  into  one-quarter  its  bulk  of  a  25  per  cent, 
solution  of  magnesium  sidphate. 

(6)  Sodium  sulphate.  Blood  is  mixed  on  leaving  the  vessels  vriih  an  equal 
volume  of  half-satiirated  sodium  sulphate  solution.  The  plasma  obtained  in 
either  of  these  ways  is  known  as  salt-plasma.  Clotting  is  indefinitelj^  delayed  in 
either  case,  but  it  can  be  induced  by  suitable  treatment  of  the  separated  plasma. 

(6)  Methods  depending  on  Decalcification  of  the  Blood.  Oxalate  plasma  is 
obtained  by  receiving  blood  into  a  solution  of  sodium  oxalate  so  that  the  total 
blood  contains  1  per  1000  of  the  oxalate.  Instead  of  oxalate  we  may  use  sodium 
fluoride,  the  proportion  in  this  case  being  3  parts  of  NaF  per  1000  blood. 

(7)  Methods  depending  on  the  Use  of  certain  Substances  of  Animal  Origin. 
(a)  Peptone  plasma  is  obtained  by  injecting  rapidly  into  the  veins  of  a  dog  or 
cat  in  a  fasting  condition  a  solution  of  commercial  peptone  in  the  proportion  of 
0'3  grm.  peptone  per  Idlo  of  the  animal.  The  effect  of  this  injection  is  to  cause 
a  rapid  fall  of  blood-pressure  and  hurried  respiration,  and  the  animal  then 
passes  into  a  state  of  coma  which  may  last  an  hour  or  two.  On  draTsing  off  the 
blood  immediately  after  the  fall  of  pressure  has  taken  place  it  is  found  to  be 
uncoagulable,  and  cell-free  plasma  can  be  obtained  from  it  by  the  use  of  the 
centrifuge.  A  number  of  animal  extracts  act  in  a  somewhat  similar  fasliion,  such 
as  extract  of  crayfish,  of  mussels,  &c. 

{h)  Leech  extract  or  hirudin  plasma.  Peptone  is  only  efficacious  in  retarding 
clotting  when  it  is  injected  into  the  animal's  veins  directly,  and  has  no  influence 
in  tliis  direction  if  it  be  mixed  with  the  blood  as  it  flows  out  of  the  vessels.  It 
has  long  been  familiar  to  phj'sicians  that  the  bites  made  by  leeches  continue  to 
bleed  for  a  considerable  time,  and  it  was  shoAvn  by  Haycraft  that  tliis  is  due  to 
the  presence  of  an  anti -coagulating  substance  in  the  buccal  glands  of  the  leech. 
This  substance,  wliich  has  the  properties  of  an  albumose,  can  be  extracted  by 
boiling  from  the  anterior  half  of  the  leech.  It  will  destroy  the  coagulability  of 
the  blood  either  when  injected  into  the  blood-stream  or  when  blood  is  received 
into  a  solution  of  hirudin. 

By  any  of  these  methods  it  is  possible  to  obtain  blood-plasma  free 
from  formed  elements.  The  conditions  which  will  bring  about 
coagulation  in  such  plasmata  are  strikingly  diverse.  Thus  in  cooled 
plasma  a  simple  rise  of  temperature  is  often  sufficient  to  bring  about 
coagulation.  If,  however,  the  cooled  plasma  be  filtered  several  times 
through  two  thicknesses  of  filter- paper,  being  kept  at  a  temperature  of 
about  1°C.  during  the  whole  time,  it  loses  this  spontaneous  coagulability 
on  w^arming.  It  can  still  be  made  to  clot  by  the  addition  of  certain 
substances  such  as  blood-serum  or  the  washings  of  a  blood-clot,  and 
in  some  cases  by  the  addition  of  tissue  extracts. 

Oxalate  plasma  clots  on  simple  addition  of  lime  salts.  Sodium 
sulphate  plasma  clots  on  dilution.  Magnesium  sulphate  plasma  will 
not  clot  on  dilution,  but  needs  in  addition  the  presence  of  some  blood- 
serum  or  some  substance  derived  from  blood-serum.  In  both  these 
cases  tissue  extracts  have  no  influence.     By  a  careful  study  of  one  or 


THE  COAGULATION  OF  THE  BLOOD  949 

two  forms  of  plasma  we  can  arrive  at  a  conception  of  the  processes  of 
coagulation  which,  enables  us  to  understand  the  behaviour  of  all  these 
various  types.  We  may  take  as  our  type  oxalate  plasma.  Oxalate 
plasma,  as  procured  by  centrifuging  a  specimen  of  horse's  blood  con- 
taining O'l  per  cent,  sodium  oxalate,  is  a  clear  yellow  fluid,  perfectly 
free  from  formed  elements,  which  evinces  no  tendency  to  clot.  On 
adding  a  drop  of  calcium  chloride  to  such  plasma  we  see  that  it  contains 
an  excess  of  oxalate  from  the  production  of  a  precipitate  of  calcium 
oxalate.  If  calcium  chloride  be  added  drop  by  drop  so  as  to  be  present 
in  slight  excess  and  the  plasma  be  then  kept  warm,  it  will  clot  within 
a  time  varying  from  a  few  minutes  to  an  hour.  The  clot  thus  formed 
is  perfectly  firm  and  the  vessel  can  be  inverted  wthout  any  of  its 
contents  flowing  out.  Very  often  no  retraction  of  the  clot  takes  place, 
but  if  it  be  pressed  with  a  glass  rod  or  with  the  fingers  a  clear  serum 
is  squeezed  out  and  a  mass  of  pure  fibrin  remains.  The  place  of  lime 
can  be  taken  by  strontium,  but  barium  and  magnesium  are  powerless 
to  initiate  clotting.  We  must  therefore  conclude  that  the  presence 
of  a  soluble  calcium  salt  is  one  factor  of  those  necessary  for  coagulation. 
This  is  borne  out  by  the  fact  that  a  similar  uncoagulable  blood  is 
produced  by  the  action  of  sodimri.  fluoride.  Some  difficulty,  however, 
was  felt  when  it  was  found  that  sodium  citrate  might  be  used  instead 
of  sodium  oxalate  or  chloride,  since  sodium  citrate  does  not  produce 
in  the  blood  any  precipitate  of  insoluble  lime  salts.  Here  therefore 
we  have  a  blood  containing  lime  in  solution  and  yet  rmcoagulable. 
The  difficulty  has  been  cleared  up  by  the  work  of  Sabbatani  and 
C.  J.  Martin.  When  sodium  citrate  is  added  to  a  lime  salt  a  double 
salt  of  sodium  calcium  citrate  is  formed  in  which  the  calcium  is  in  the 
anion  and  forms  part  of  the  acidic  radical.  The  mere  presence  of 
dissolved  calcium  is  not  sufiicient  for  clotting  to  take  place.  It  is 
necessary  that  the  calcium  should  be  in  the  form  of  a  salt  and  in  an 
ionised  condition,  such  as  calcium  chloride  or  calcium  sulphate. 

Though  calcium  is  a  necessary  condition  for  the  occurrence^  of 
coagulation,  it  cannot  be  regarded  as  a  precursor  of  the  protein  fibrin. 
If  the  composition  of  the  plasma  before  coagulation  has  been  set  up 
be  compared  with  that  of  the  serum  which  has  separated  from  the 
clot,  it  is  found  that  plasma  contains  a  protein,  jihrinogen,  not  repre- 
sented in  the  serum,  which  must  therefore  be  the  precursor  of  fibrin. 
Fibrinogen  belongs  to  the  class  of  globulins.  It  can  be  separated  from 
oxalate  plasma  by  half-saturation  with  common  salt.  An  equal 
volume  of  a  saturated  solution  of  sodimn  chloride  is  added  to  plasma 
so  that  the  whole  mixture  contains  16  per  cent,  sodium  chloride.  The 
fluid  gradually  becomes  turbid  from  the  production  of  a  precipitate 
which,  at  first  granular,  rapidly  aggregates  to  form  a  stringy, 
slimy  solid,  and  on  stirring  aggregates  into  masses  which  adhere 


950  PHYSIOLOGY 

to  the  glass  rod  used  for  stirrino;.  This  mass  can  be  taken  out 
of  the  fluid,  washed  by  kneading  with  half-saturated  sodium 
chloride  solution,  and  then  redissolved  by  the  addition  of  distilled 
water.  With  the  salt  adhering  to  the  precipitate  a  dilute  saline  fluid 
is  formed  in  which  the  fibrinogen  is  soluble.  The  fibrinogen  can  be 
purified  by  repeating  the  precipitation  and  solution,  though  it  tends 
to  lose  its  solubility  in  the  process,  so  that  purification  is  always 
attended  ^vith  some  loss.  The  solutioii  of  fibrinogen  thus  obtained  is 
perfectly  clear  and  colourless.  On  warming,  practically  the  whole  of 
its  protein  is  thrown  dow^l  between  56°  and  60°  C.  The  same  precipi- 
tate is  produced  on  heating  the  original  plasma,  whereas  serum 
obtained  by  the  expression  of  the  clot  does  not  give  any  precipitate  on 
heating  until  a  temperature  of  68°  to  70°  C.  is  reached.  If  a  solution 
of  fibrinogen,  obtained  by  precipitating  vdth  sodimn  chloride  and 
dissolving  in  distilled  water,  be  treated  with  a  drop  or  two  of  calcium 
chloride  it  rapidly  clots  with  the  formation  of  typical  fibrin.  We  might 
conclude  from  this  experiment  that  fibrin  was  a  compound  produced 
by  the  union  of  calcium  salts  "s^ith  fibrinogen.  Further  experiments 
show,  however,  the  untenability  of  this  hypothesis.  If  the  fibrinogen 
has  been  thoroughly  purified  by  repeated  precipitation  and  re-solution, 
calcium  salts  are  found  to  have  entirely  lost  their  power  of  causing 
coagulation.  Such  a  purified  fibrinogen  can  still  be  made  to  clot  by 
the  addition  either  of  serum  or  of  the  washings  of  a  blood-clot,  or  of 
the  watery  extract  of  alcohol-coagulated  serum.  This  power  of  serum 
to  convert  fibrinogen  into  fibrin  is  due  to  the  presence  in  it  of  minute 
quantities  of  a  substance  which  has  been  designated  as  '  fibrin 
ferment '  or  thrombin.  It  has  been  regarded  as  a  ferment  because  it 
is  active  in  minimal  quantities  and  is  stated  not  to  be  appreciably 
used  up  in  the  process  of  clotting.  Thus  if  we  add  some  serum  to  a 
fibrinogen  solution  we  can  cause  clotting,  and  then  on  squeezing  the 
clot  obtain  a  serum  which  will  bring  about  coagulation  when  added  to 
a  fresh  portion  of  fibrinogen.  Considerable  doubt,  however,  has  been 
thrown  on  the  ferment  nature  of  thrombin  by  the  recent  work  of 
Rettger  in  Howell's  laboratory.  Rettger  shows,  in  the  first  place,  that 
the  statement  of  the  preceding  sentence  is  only  true  if  a  large  excess 
of  thrombin  solution  be  made  use  of  in  the  first  instance.  If  small 
quantities  of  thrombin  solution  be  added  to  large  quantities  of  plasma 
or  of  pure  solutions  of  fibrinogen,  the  amount  of  fibrin  obtained  is 
proportional  to  the  amount  of  thrombin  added.  This  is  shown  in 
the  follo^ving  experiment : 

5  drops  of  thrombin  gave  0-2046  grm.  fibrin. 

10     „  „  0-3573     „ 

20      „  „  0-6089     „ 

40     „  „  1-5872     „ 


THE  COAGULATION  OF  THE  BLOOD  951 

Moreover  the  action  of  thrombin  on  fibrinogen  solutions  is  abnost 
independent  of  temperature,  occurring  practically  as  rapidly  at  17°  C. 
as  at  40°  C.  It  has  been  found  that  there  is  only  a  slight  increase  in 
the  rate  of  action  of  snake  venom  on  fibrinogen  solutions  on  warming 
from  20°  to  40°  C.  Rettger  therefore  regards  fibrin  as  formed  by  the 
union  of  thrombin  and  fibrinogen.  This  union  is  apparently  very 
unstable.  If  fibrin  be  extracted  with  a  3  per  cent,  salt  solution  for 
some  time,  part  of  it  goes  into  solution,  and  the  solution  is  found  to 
contain  thrombin.  In  the  same  way  the  thrombin  may  be  re-extracted 
from  the  fibrin  if  the  latter  be  allowed  to  putrefy. 

From  all  the  different  kinds  of  plasma  which  have  been  enumerated 
above  the  purified  fibrinogen  can  be  obtained  by  the  use  of  sodium 
chloride,  and  in  every  case  can  be  made  to  clot  by  the  addition  of 
serum  or  of  a  solution  of  thrombin.  The  last  change  in  the  act  of 
clotting  is  therefore  the  change  from  fibrinogen  to  fibrin,  and  this 
event  is  brought  about  by  the  intervention  of  thrombin.  It  cannot 
be  at  this  stage  of  the  process  that  the  calcium  salts  exercise  their 
influence,  since  '  fibrin  ferment '  or  thrombin  will  cause  the  coagulation 
of  fibrinogen  in  the  total  absence  of  soluble  calcium  salts  and  even 
in  the  presence  of  a  slight  amount  of  ammonium  oxalate.  Moreover 
Hammarsten  has  shown  that  the  calcium  content  of  fibrin  is  no  greater 
than  that  of  the  fibrinogen  from  which  it  is  formed. 

The  fact  that  a  solution  of  pure  fibrinogen  is  made  to  clot  by 
thrombin  and  by  this  alone  renders  such  a  solution  an  excellent 
reagent  for  the  presence  of  the  '  ferment.'  By  this  means  we  can  show 
that  thrombin  is  absent  in  circulating  blood.  If  blood  be  received 
direct  from  the  vessels  into  absolute  alcohol  and  the  precipitate, 
after  coagulation  by  alcohol,  be  extracted  by  water,  the  extract  is 
found  to  contain  no  trace  of  ferment.  The  same  statement  applies 
to  fresh  oxalate  plasma.  If,  however,  oxalate  plasma  be  made  to 
clot  by  the  addition  of  calcium  salts,  the  serum  squeezed  from  the 
clot  is  found  to  contain  thrombin.  In  the  process  of  coagulation  there- 
fore not  only  is  there  a  conversion  of  fibrinogen  to  fibrin,  but  there  is  an 
actual  formation  of  the  agent  which  is  responsible  for  this  change, 
namely,  thrombin  or  fibrin  ferment.  Our  next  step  therefore  must  be 
to  inquire  into  the  precursors  of  the  thrombin  and  the  conditions  of 
its  formation. 

If  oxalate  plasma  be  cooled  to  0°  C.  for  two  or  three  days  a  scanty 
granular  precipitate  is  produced.  This  can  be  centrifuged  ofi  or 
separated  by  filtration  through  several  thicknesses  of  paper.  It  is 
then  found  that  the  remaining  plasma  can  no  longer  be  made  to 
coagulate  by  the  addition  of  lime  salts,  although  it  still  contains 
fibrinogen,  which  is  converted  into  fibrin  on  the  addition  of  thrombin. 
If  the  precipitate  be  collected  and  treated  with  calcium  chloride  and 


952  PHYSIOLOGY 

the  mixture  added  to  the  oxalate  plasma  the  latter  clots.  The  same 
effect  is  produced  if  the  precipitate  ]}lus  calcium  be  added  to  a  pure 
solution  of  fibrinogen.  We  must  conclude  that  the  precipitate,  though 
itself  not  fibrin  ferment,  will  give  rise  to  fibrin  ferment  on  treatment 
with  lime  salts.  It  was  therefore  designated  by  Hammarsten  '  pro- 
thrombin,' and  regarded  as  the  precursor  of  thrombin. 

Thus  far  practically  all  workers  on  the  subject  are  agreed. 
Coagulation  of  the  blood  is  due  finally  to  the  coagulation  of  thrombin 
and  fibrinogen.  The  fibrinogen  is  present  as  such  in  the  circulating 
plasma.  Thrombin  is  not  contained  in  the  circulating  blood,  but  is 
produced  from  some  precursor  or  precursors  after  the  blood  has  been 
shed.  For  the  production  of  thrombin  the  presence  of  calcium  salts 
is  necessary.  Further  research  on  the  nature  of  the  precursor  pro- 
thrombin has  shown  that  the  matter  is  not  quite  so  simple  as  imagined 
by  Hammarsten.  In  the  following  account  we  shall  adhere  chiefly 
to  the  account  as  given  by  Morawitz,  reserving  most  of  the  criticisms 
and  limitations  to  be  made  to  this  theory  for  the  historical  sketch  of 
the  theories  of  clotting  at  the  end  of  this  section. 

Oxalate  plasma  which  has  been  separated  from  the  precipitate  of 
prothrombin  can  be  made  to  coagulate  by  the  addition  of  extracts  of 
almost  any  animal  tissues  together  with  lime  salts,  and  these  there- 
fore were  supposed  to  contain  prothrombin  similar  to  that  obtained 
by  cooling  oxalate  plasma.  These  extracts  even  on  mixture  with 
calcium  are,  however,  without  effect  on  pure  solutions  of  fibrinogen, 
and  moreover  the  precipitate  produced  by  cold,  if  thoroughly  washed 
before  treatment  with  lime  salts,  loses  its  power  of  evoking  coagulation 
in  fibrinogen  solutions.  Prothrombin  is  therefore  unable  by  itself, 
even  on  addition  of  lime  salts,  to  produce  fibrin  ferment,  but  needs 
the  co-operation  of  some  other  substance  which  is  contained  in  oxalate 
plasma  and  which  generally  adheres  in  sufficient  quantities  to  the 
precipitate  produced  by  cooling.  Three  factors  are  therefore  necessary 
for  the  production  of  fibrin  ferment :  firstly,  lime  salts  ;  secondly,  a 
substance  present  in  the  precipitate  of  prothrombin  as  well  as  in  most 
animal  tissues  ;  and  thirdly,  a  substance  present  in  solution  in  oxalate 
plasma.  These  two  latter  substances  have  been  designated  by 
Morawitz  thrombokinase  and  thrombogen.  Thrombokinase  is  con- 
tained in  tissues  and  also  in  the  blood-platelets.  It  can  be  obtained 
by  extraction  of  the  stroma  of  the  red  blood-corpuscles  or  of  the 
bodies  of  lymph-cells  or  leucocytes.  Separation  of  the  blood-platelets 
by  cooling  in  the  form  of  the  disc-like  precipitation  abolishes  the 
spontaneous  coagulability  of  any  form  of  plasma.  The  thrombogen 
is  contained  in  solution  in  oxalate  plasma.  It  is  therefore  con- 
cluded that  when  blood  leaves  the  vessels  there  is  a  disintegration  of 
the  blood-platelets  with  the  liberation  of  thrombokinase.     This  acts 


THE  COAGULATION  OF  THE  BLOOD  953 

upon  thrombogen  in  the  presence  of  lime  salts  and  produces  thrombin. 
By  tlie  intermediation  of  the  thrombin  the  fibrinogen  also  present  in 
solution  in  the  plasma  is  converted  into  fibrin.  The  changes  occurring 
in  shed  blood  and  resulting  in  the  production  of  a  clot  are  therefore 
mainly  concerned  with  the  production  of  the  fibrin  ferment.  This 
view  of  the  essential  characters  of  coagulation  is  borne  out  by  observa- 
tions on  other  forms  of  plasma,  especially  of  plasma  obtained  from 
birds'  blood.  This  when  obtained  with  scrupulous  cleanliness  so  as 
to  avoid  any  contamination  with  dust  or  with  the  tissues  remains 
permanently  uncoagulable.  In  the  plasma  got  by  centrifuging  the 
blood  no  blood-platelets  are  to  be  seen,  and  no  precipitate  is  produced 
by  exposure  to  a  temperature  of  0°  C.  We  may  say  therefore  that 
blood-platelets  with  their  contained  thrombokinase  are  absent  from 
birds'  blood,  and  with  them  the  property  of  spontaneous  coagulability. 
It  is  also  free  from  fibrin  ferment,  but  contains  thrombogen  as  well  as 
soluble  lime  salts.  It  is  only  necessary  therefore  to  add  thrombokinase 
in  the  shape  of  a  watery  extract  of  any  tissue  in  order  to  cause  the 
appearance  of  fibrin  ferment  and  the  conversion  of  the  fibrinogen 
already  present  in  the  plasma  into  fibrin. 

In  every  case  the  initiation  of  the  act  of  clotting  would  seem  to 
depend  on  the  setting  free  of  thrombokinase  in  the  plasma.  In 
mammalian  blood,  although  thrombokinase  can  be  derived  from  red  or 
white  corpuscles,  we  have  no  reason  to  believe  that  there  is  any 
appreciable  disintegration  of  these  formed  elements  when  the  blood 
leaves  the  vessels.  In  oxalate  blood  leucocytes  can  be  seen  alive  and 
exercising  amoeboid  movements  two  or  three  days  after  the  blood  has 
left  the  vessels,  and  although  certain  observers  have  assumed  the 
presence  of  explosive  corpuscles  which  break  up  directly  the  blood 
leaves  the  vessels,  the  presence  of  such  corpuscles  in  the  higher  animals 
has  not  been  demonstrated,  though  in  some  invertebrata  they  are 
certainly  present.  The  sole  source  therefore  of  the  thrombokinase  is 
the  very  perishable  formed  elements  of  which  we  have  spoken  as  the 
blood-platelets.  The  very  existence  of  this  element  is  doubtful  in 
normal  blood.  What  is  certain  is  that  any  slight  change  in  the  plasma, 
whether  due  to  contact  with  a  foreign  object  or  to  cooling  of  the  blood, 
causes  the  appearance  of  these  elements.  The  first  act  therefore  in 
coagulation  is  the  appearance  of  the  blood-platelet  and  its  disintegra- 
tion with  the  setting  free  of  thrombokinase.  The  part  played  by  the 
platelets  in  coagulation  is  of  great  importance  in  maintaining  the 
integrity  of  the  vascular  system.  If  a  fine  needle  be  thrust  through 
the  wall  of  a  venous  capillary  which  is  kept  under  observation  by  the 
microscope  it  will  be  seen  that  the  blood,  as  it  flows  past  the  injured 
spot,  deposits  blood-platelets  on  the  side  of  the  puncture.  These 
aggregate  to  form  a  plug  closely  adherent  to  the  wall  of  the  vessel,  which 


954  PHYSIOLOGY 

QfEectively  prevents  any  escape  of  the  contents  of  the  capillary.  The 
blood-platelets  fuse  so  as  to  form  a  mass  of  fibrin,  and  later  on  by  the 
growth  of  the  adjacent  endothelial  cells  the  thrombus  is  organised, 
converted  into  connective  tissue,  and  covered  with  a  layer  of  endo- 
thelium continuous  with  the  rest  of  the  vessel.  The  same  process 
occurs  when  any  part  of  the  lining  membrane  of  a  large  vessel  is  injured. 
Thus  destruction  of  a  patch  of  endothelium  in  a  vein  leads  to  the 
deposition  of  blood-platelets  over  the  patch  and  the  formation  of  a 
'  thrombus  '  adherent  to  the  wall.  From  this  thrombus  coagulation 
may  spread  through  the  rest  of  the  contents  of  the  vessel  and  produce 
thrombosis  of  the  whole  vein.  Under  healthy  conditions  the  thrombus 
serves  simply  to  cover  the  bare  area  in  the  wall  of  the  vein  and  is 
grown  over  later  by  endothelium,  so  restoring  the  integrity  of  the 
vessel  wall.  If  we  believe  in  the  pre-existence  of  blood-platelets  in 
the  circulating  blood  we  must  assume  the  first  act  in  coagulation  to  be 
the  disintegration  of  these  elements  and  the  setting  free  of  thrombo- 
kinase.  If  we  disbelieve  in  their  pre-existence  the  first  act  in  coagula- 
tion must  be  a  change  in  the  plasma  itself  (which  perhaps  can  be 
regarded  as  a  dropsical  protoplasm),  leading  to  the  separation  of  an 
unstable  substance,  thrombokinase,  in  the  form  of  a  disc-like  precipitate 
which  rapidly  undergoes  further  changes,  reacting  with  the  thrombogen 
remaining  in  solution  in  the  plasma  with  the  production  of  fibrin 
ferment. 

Why  does  the  blood  not  clot  in  the  vessel  ?  No  theory  of  coagula- 
tion can  be  satisfactory  which  does  not  account  at  the  same  time  for 
the  preservation  of  the  fluidity  of  the  circulating  blood.  One  factor  at 
any  rate  in  the  prevention  of  intravascular  clotting  must  be  the  nature 
of  the  surfaces  with  which  the  blood  comes  in  contact.  The  blood,  even 
of  mammals,  can  be  prevented  for  a  time  from  clotting  if  it  be  kept 
carefully  from  contact  with  any  foreign  substance  which  is  wetted  by 
it,  as,  for  instance,  when  it  is  received  into  vessels  free  from  dust  and 
coated  with  a  layer  of  oil  or  paraffin.  On  the  other  hand,  free  contact 
with  such  substances,  as  occurs  when  the  blood  is  whipped,  materially 
hastens  the  process  of  coagulation.  One  must  therefore  conclude 
that  mere  contact  with  a  foreign  body  has  a  direct  destructive  action 
either  on  the  plasma  leading  to  the  formation  of  blood-platelets,  or 
on  the  latter,  leading  to  their  disintegration  and  the  discharge  of 
thrombokinase.  Birds'  blood,  for  instance,  can  be  made  to  clot  with- 
out the  addition  of  tissue  juice  if,  by  increasing  the  mechanical  insult, 
as  by  violent  whipping,  filtration  through  a  clay  cell,  or  addition  of 
water,  we  destroy  the  leucocytes  and  red  blood-corpuscles,  so  leading 
to  the  liberation  of  their  contained  thrombokinase.  Another  factor 
is  probably  the  presence  of  what  we  may  call  antithrombins  in 
circulating  blood.    Although  evidence  of  the  existence  of  these  bodies 


THE  COAGULATION^  OF  THE  BLOOD  955 

is  still  somewhat  uncertain,  the  fact  that  blood-serum  often  has  an 
inhibitory  effect  on  the  action  of  a  solution  of  fibrin  ferment  points 
to  the  presence  in  the  serum  of  some  antibody  to  the  ferment.  One 
must  assume  too  that  processes  of  disintegration  are  continually 
occurring  in  the  blood  and  involving  the  plasma,  blood-platelets,  and 
leucocytes,  just  as  we  know  them  to  affect  the  red  blood-corpuscles. 
In  the  healthy  animal  the  liberation  of  thrombokinase  which  must 
take  place  under  these  circumstances  has  no  influence  in  producing 
clotting.  The  organism  therefore  must  possess  means  of  neutrahsing 
the  presence  of  small  quantities  either  of  kinase  or  of  fibrin  ferment. 
When  small  quantities  of  either  of  these  substances  are  injected  into 
the  blood-stream  no  coagulation  takes  place,  but  the  blood  obtained 
after  the  injection  clots  with  less  readiness  than  before,  a  change 
which  can  only  be  ascribed  to  the  production  in  the  body  of  antikinase 
or  of  antithrombin.  This  production  of  anticoagulins  must  be 
continually  taking  place  and  must  co-operate  in  the  preservation  of 
the  fluid  state  of  the  blood  while  in  the  vessels. 

INTRAVASCULAR  CLOTTING.  On  account  of  the  protective 
mechanisms  with  which  the  animal  organism  is  endowed  the  production 
of  clotting  in  the  vessels  of  the  living  animal  is  not  readily  effected  by 
the  injection  of  thrombin.  Solutions  obtained  by  Schmidt's  method 
from  alcohol- coagulated  serum  are  generally  without  effect,  and  we 
have  to  inject  a  very  strong  solution  of  thrombin  or  the  strong  fibrin 
ferment  contained  in  the  venom  of  certain  snakes  in  order  to  bring 
about  coagulation  of  the  blood  in  the  vessels.  Intravascular  clotting 
is  more  easily  effected  by  the  injection  of  thrombokinase.  It  was 
shown  by  Wooldridge  that  normal  saline  extracts  of  tissues  rich  in 
cells,  such  as  the  thymus,  Ipuph-glands,  or  testis,  causes  invariably 
extensive  thrombosis.  If  such  extracts  be  acidified  with  acetic  acid 
a  precipitate  is  produced  which  is  soluble  in  dilute  alkalies,  and  on 
gastric  digestion  yields  a  precipitate  rich  in  phosphorus.  Alkaline 
solutions  of  the  acid  precipitate  bring  about  intravascular  clotting 
when  injected  into  the  blood-stream.  According  to  Wooldridge  the 
injected  substance  takes  part  in  the  formation  of  the  clot,  and  he 
therefore  gave  it  the  name  of  '  tissue  fibrinogen.'  It  is  usual  to  regard 
these  tissue  fibrinogens  as  nucleo-proteins.  They  are  certainly  rich 
in  lecithin,  and  the  precipitate  obtained  from  them  on  gastric  digestion 
may  contain  as  much  as  25  per  cent,  of  this  substance.  They  must 
be  derived  either  from  the  cytoplasm  or  from  the  interstitial  fluid  of 
the  tissues,  and  it  is  still  doubtful  whether  we  are  justified  in  giving 
them  the  name  of  nucleo-proteins  or  whether  we  should  not  rather 
classify  them  with,  the  phospho-proteins  which  play  so  great  a  part 
in  the  building  up  of  the  cytoplasmic  part  of  the  cell.  We  may 
explain  the  action  of  these  tissue  extracts  as  due  to  their  containing 


956  PHYSIOLOGY 

thrombokinase.  Their  injection  would  resemble  therefore  the  libera- 
tion of  thrombokinase  which  normally  occurs  when  blood  leaves  the 
vessels.  More  difficult  to  understand  is  the  result  of  injecting  small 
amounts  of  these  tissue  extracts  or  large  amounts  in  small  doses. 
A  minute  quantity  of  tissue  extract  injected  into  the  blood-stream 
produces,  not  intravascular  clotting,  but  a  delay  of  the  coagulation 
time.  Repeated  injections  of  small  doses  may  absolutely  annul  the 
coagulability  of  the  blood,  which  can  be  collected  by  opening  the 
blood-vessels  and  will  remain  unclotted  for  many  days.  The  same 
double  effect  may  be  observed  even  with  a  larger  dose.  In  rabbits 
and  in  dogs  after  a  full  meal  the  intravascular  coagulation  which 
occurs  is  complete,  extending  through  the  whole  vascular  system.  If, 
however,  the  injection  be  made  into  a  fasting  dog  the  thrombosis 
produced  is  limited  to  the  portal  vein.  There  is  a  sudden  fall  of  blood- 
pressure,  from  which  the  animal  gradually  recovers.  If  a  vessel  be 
opened  during  the  period  of  low  pressure  the  blood  which  flows  out 
is  totally  uncoagulable,  and  if  the  animal  be  killed  at  this  time  a 
clot  will  be  found  filling  up  the  whole  portal  vein.  Wooldridge 
described  these  two  effects  of  injection  of  tissue  extracts,  namely,  the 
coagulation  and  the  loss  of  coagulability,  as  the  positive  and  negative 
phases  respectively.  Since  the  negative  phase  has  not  been  observed 
in  any  form  of  extra-vascular  plasma  we  must  ascribe  it  to  a  reaction 
on  the  part  of  the  living  cells,  and  probably,  since  it  is  so  rapid  in  its 
establishment,  to  the  action  of  the  cells  lining  the  blood-vessels.  The 
interest  of  these  observations  lies  in  the  relation  which  they  bear  to 
the  production  of  immunity.  If  a  toxin  such  as  that  of  diphtheria 
or  tetanus  be  injected  into  an  animal,  an  anti-toxin  is  produced  in  the 
course  of  two  or  three  days.  If  now  further  doses  of  toxin  be  injected 
its  fiist  effect  is  to  destroy  the  whole  of  the  anti-toxin  present  in  the 
circulating  blood.  In  the  course  of  a  day  or  two  the  anti-toxin 
gradually  returns,  and  at  the  end  of  three  days  is  found  in  larger 
quantities  in  the  blood  than  were  present  before  the  second  injection. 
Every  toxin  has  therefore  a  positive  as  well  as  a  negative  phase  of 
action.  Tissue  extracts  in  their  effect  on  coagulation  have  a  similar 
positive  and  negative  phase,  but  these  phases  are  established  within 
a  few  seconds  instead  of  taking  two  or  three  days  for  their  develop- 
ment. One  cannot  but  believe  that  a  renewed  study  of  the  conditions 
of  intravascular  clotting  might  shed  important  light  on  the  chemical 
mechanism  of  production  of  immunity. 

FATE  OF  THE  FIBRIN  FERMENT.  The  substances  which  interact 
for  the  production  of  thrombin  in  shed  blood  as  well  as  thrombin 
itself  are  not  entirely  used  up  in  the  process  of  clotting.  Blood-serum, 
though  free  from  fibrinogen,  contains  traces  of  thrombokinase  (which 
can  be  precipitated  by  the  addition  of  dilute  acetic  acid)  and  throm- 


THE  COAGULATION  OF  THE  BLOOD  957 

bogen,  as  well  as  a  fairly  strong  solution  of  thrombin.  Thrombin,  how- 
ever, rapidly  disappears  from  serum,  so  that  a  blood-serum  which  has 
been  kept  for  two  or  three  days  may  be  almost  free  from  fibrin  ferment. 
Such  a  serum  can  be  reactivated  by  the  addition  of  small  traces  either 
of  acid  or  alkali.  It  has  been  suggested  that  the  thrombin  undergoes 
a  modification  into  an  inactive  form  which  is  called  metathramhin. 
This  substance  has  no  relation  to  the  precursors  of  fibrin  ferment 
which  we  have  already  considered.  It  is  unaltered  by  lime  salts  or 
by  the  addition  of  thrombokinase,  but  can  be  reconverted  into 
thrombin  by  means  of  acids  or  alkalies.  According  to  Rettger 
the  disappearance  of  thrombin  from  serum  is  due  to  its  combi- 
nation with  some  of  the  proteins  of  the  serum.  This  combination, 
like  that  of  thrombin  with  fibrinogen  to  form  fibrin,  is  unstable 
and  can  be  broken  up  by  the  action  of  alkalies,  acids,  or  even 
of  putrefaction.  Thrombin  itself  seems  to  be  extremely  stable  and 
will  even  ^^^thstand  the  temperature  of  boiling  water  for  a  short 
time.  If  solutions  containing  thrombin  be  evaporated  to  dryness  the 
dry  residue  can  be  heated  to  135°  C.  without  destruction  of  the 
thrombin. 

We  are  now  in  a  position  to  see  how  far  the  theory  of  coagulation 
which  we  have  evolved  from  a  study  of  two  forms  of  plasma  will 
serve  to  explain  the  behaviour  of  the  many  other  kinds  of  plasma 
which  have  been  the  subject  of  investigation. 

Cooled  plasma  contains  the  thrombokinase  in  the  form  of  blood- 
platelets  or  a  disc-like  precipitate.  This  precipitate  can  be  separated 
by  centrifuging  at  a  low  temperature  or  by  filtration.  The  remaining 
plasma  contains  only  thrombogen,  lime  salts,  and  fibrinogen,  and 
can  be  made  to  clot  by  the  addition  of  tissue  extracts  or  of  fibrin 
ferment,  but  will  not  clot  on  warming. 

In  SODIUM  SULPHATE  PLASMA  the  interaction  of  the  fibrin  factors 
is  merely  impeded  by  the  excess  of  salt.  All  are  still  present,  and  it 
is  therefore  sufficient  merely  to  dilute  the  plasma  in  order  to  produce 
clotting. 

Magnesium  sulphate  plasma  behaves  somewhat  differently.  If 
the  blood  be  received  directly  into  magnesium  sulphate  solution  and 
the  mixture  centrifuged  while  still  warm,  a  clear  magnesium  sulphate 
plasma  is  obtained  which  will  clot  on  simple  dilution.  If  the  blood  be 
left  for  twenty-four  hours  before  centrifuging,  the  plasma  will  not  clot 
on  dilution  nor  on  the  addition  of  tissue  extracts.  It  contains 
fibrinogen  only  and  is  therefore  an  excellent  reagent  for  the  presence 
of  fibrin  ferment.  Magnesium  sulphate  not  only  hinders  the  inter- 
action of  the  fibrin  factors  but  actually  slowly  precipitates  the  thrombo- 
kinase, so  that  if  time  be  allowed  for  this  precipitation  to  be  complete 
the  remaining  plasma  contains  only  fibrinogen. 


958  PHYSIOLOGY 

Sodium  fluoride  plasma  might  be  expected  to  act  like  oxalate 
plasma  since  sodium  fluoride  is  a  precipitant  of  lime  salts.  This  salt 
has,  however,  the  additional  property  of  causing  a  certain  amount  of 
fixation  of  the  formed  elements  of  the  blood  as  well  as  of  the  blood- 
platelets.  If  it  be  thoroughly  centrifuged  so  that  the  plasma  is 
obtained  free  from  these  constituents  it  will  no  longer  clot  vnth  lime 
salts  *  nor  even  with  lime  salts  jylus  tissue  extracts,  but  will  clot 
readily  on  addition  of  thrombin.  Although  it  still  contains  a  certain 
amount  of  thrombogen,  this  is  entangled  and  carried  down  in  the 
precipitate  of  calcium  fluoride  which  is  produced  by  the  addition  of 
lime  salts,  so  that  the  thrombokinase  has  nothing  on  which  to  exercise 
its  effect.  Sodium  fluoride  plasma  is  therefore  useful,  like  magnesium 
sulphate  plasma,  as  a  test  for  the  presence  of  thrombin.  If  water  be 
added  to  the  sodium  fluoride  blood  so  as  to  destroy  some  of  the  formed 
elements  and  liberate  their  constituents  into  the  plasma,  it  is  possible 
to  produce  clotting  by  the  simple  addition  of  lime  salts. 

Hirudin  plasma.  The  action  of  hirudin  is  that  of  an  anti-thrombin. 
It  apparently  combines  with  and  neutralises  fibrin  ferment.  Hirudin 
plasma  can  therefore  be  made  to  clot  by  the  addition  of  fibrin  ferment 
in  sufficiently  large  quantities  to  combine  with  all  the  hirudin  present 
and  leave  an  excess  over  in  the  fluid. 

Peptone  plasma  presents  many  difficulties  in  the  explanation 
of  its  behaviour.  Peptone  itself  has  apparently  no  influence  on  the 
coagulation  of  the  blood.  Blood  received  into  peptone  solution 
clots  as  rapidly  as  when  received  into  salt  solution.  On  the  other  hand, 
if  blood  be  received  into  peptone  blood  obtained  by  the  injection  of 
large  doses  of  peptone  into  the  veins  of  another  animal,  the  mixture 
does  not  clot,  showing  that  peptone  blood  contains  some  substance 
which  inhibits  the  processes  of  coagulation.  This  '  anticoagulin ' 
must  be  produced  by  the  organism  itself  as  a  result  of  the  injection 
of  peptone,  and  evidence  has  been  brought  forward  by  Delezenne  and 
others  that  the  seat  of  formation  of  the  anticoagulin  is  in  the  liver. 
Whether  the  anti-substance  partakes  of  the  characters  of  an  anti- 
thrombin  or  of  an  antikinase  has  not  yet  been  definitely  ascertained. 
Peptone  plasma  can  be  made  to  clot  by  the  addition  of  tissue  extracts 
even  in  small  quantities.  It  still  contains  all  the  fibrin  factors  since 
it  will  clot  on  simple  dilution  or  on  the  passage  of  a  current  of  carbon 
dioxide.  It  needs,  however,  the  addition  of  large  quantities  of  fibrin 
ferment  to  bring  about  coagulation. 

THE  TRANSUDATIONS 
The  earlier  work  on  the  mechanism  of  coagulation  was  largely 
carried  out  on  the  fluids  obtained  from  the  pericardial  or  pleural 
*  According  to  Rettger  this  statement  is  incorrect. 


THE  COAGULATION  OF  THE  BLOOD  959 

cavities  or  on  hydrocele  fluid  from  the  tunica  vaginalis.  These  as  a 
rule  can  be  kept  indefinitely  wnthout  clotting,  but  will  clot  readily 
on  addition  of  a  few  drops  of  blood  or  the  washings  of  a  blood-clot  or 
fibrin  ferment.  They  ^^^ll  not  clot  on  the  addition  of  tissue  extracts 
containing  thrombokinase.  Though  they  contain  leucocytes  and 
even  some  red  corpuscles,  they  are  free  from  blood- platelets.  Their 
behaviour  is  readily  explained  by  the  assumption  that  they  contain 
fibrinogen,  but  are  free  from  thrombokinase  or  thrombogen.  In  order 
to  produce  coagulation  it  is  therefore  necessary  to  add  two  fibrin 
factors,  thromboldnase  and  thrombogen,  as  happens  when  we  add 
blood,  or  to  treat  them  with  fully  formed  thrombin  or  fibrin 
ferment. 

HISTORY  OF  THE  COAGULATION  QUESTION.  It  is  not  surprising  that 
the  coagulation  of  the  blood,  with  the  antecedent  changes  which  lead  to  the  appear- 
ance of  thrombin  and  probably  represent  the  successive  stages  in  the  disintegration 
of  a  fluid  labile  protoplasmic  molecule,  i.e.  the  change  from  life  to  death  of  the 
plasma,  should  have  been  the  subject  of  a  very  large  number  of  investigations, 
and  that  even  at  the  present  time  the  interpretation  of  the  salient  facts  presents 
many  difficulties.  Some  help  may  be  given  to  the  future  clearing  up  of  these 
difficulties  by  a  study  of  tJie  steps  by  which  ovir  present  standpoint  has  been 
arrived  at.  The  universal  practice  of  bleeding  as  a  therapeutic  measure 
naturally  afforded  many  opportunities  to  physicians  for  observing  the  processes 
of  coagulation  under  diseased  as  well  as  healthy  conditions.  The  general  result 
was,  however,  in  most  cases,  a  crop  of  ill-founded  and  uncritical  theories,  and  it 
is  not  till  the  time  of  Hewson  (1772)  that  we  meet  with  investigations  of  the 
question  carried  out  on  modern  lines  with  reference  to  observation  and  experiment 
at  each  stage.  We  owe  to  Hewson  the  discovery  that  coagulation  can  be  inhibited 
indefinitely  hy  the  addition  of  neutral  salts,  such  as  sodium  sulphate,  and  it  was 
by  a  study  of  such  bloods  that  Hewson  arrived  at  the  conclusion  that  the  formed 
elements  of  the  blood  take  no  part  in  the  production  of  the  clot.  Johannes 
Miiller  in  1832  came  to  the  same  conclusion  from  a  study  of  frogs'  blood. 
This  he  diluted  with  sugar  solution  and  filtered  tluough  filter-paper.  The  large 
corpuscles  were  retained  by  the  meshes  of  the  filter-paper  and  the  clear  fluid 
which  came  through  slowly  imderwent  coagulation.  The  beginning  of  om* 
modern  ideas  on  the  subject  must  be  ascribed  to  Buchanan,  though  many  of 
the  facts  discovered  by  this  observer  escaped  general  recognition  and  were 
later  re-discovered  by  Alexander  Schmidt.  Buchanan  worked  chiefly  on  hj'dro- 
cele  fluid  and  showed  that  this  could  be  made  to  yield  fibrin  by  treatment  with 
fresh  blood  or  by  adding  it  to  the  washings  of  a  blood-clot.  He  compares  the 
action  of  the  latter  to  that  of  rennet  on  the  protein  of  milk.  His  experiments 
showed  that  '  fibrin  has  not  the  least  tendency  to  deposit  itself  spontaneously 
in  the  form  of  a  coagulum,  that,  like  albumin  and  casein,  fibrin  often  coagulates 
imder  the  influence  of  suitable  reagents,  and  that  the  blood,  like  most  other 
liquids  of  the  body  which  appear  to  coagulate  spontaneously,  only  do  so  in 
consequence  of  their  containing  at  once  fibrin  and  substances  capable  of  reacting 
upon  it  and  so  occasioning  coagulation.'  He  held  therefore  that  the  coagidation 
of  the  blood  is  due  to  the  conversion  of  a  soluble  constituent  of  the  liquor 
sanguinis  into  fibrin  by  an  action  exerted  probably  by  the  colourless  corpuscles 
and  comparable  to  the  action  which  rennet  exerts  in  effecting  the  coagulation 
of  milk.  Furthermore,  the  liquid  which  accumulates  in  certain  serous  sacs 
may  bo  made  to  yield  a  coagulum  of  fibrin  when  subjected  to  the  action  of  liquids 


960  PHYSIOLOGY 

or  solids  rich  in  the  cellular  elements  Avith  which  the  coagulent  action  appeared 
to  be  associated  (Gamgee). 

Denis  in  1856  attempted  to  separate  this  precursor  of  fibrin.  He  received 
the  blood  into  one-sixth  of  its  volume  of  saturated  sodium  sulphate,  allowed  the 
corpuscles  to  settle,  and  filtered  off  the  siipernatant  plasma.  On  saturating  this 
with  sodium  chloride  a  precipitate  was  produced  which  Denis  designated 
'  plasmine.'  This  precipitate,  on  solution  in  water,  slowly  underwent  coagulation 
and  was  apparently  split  into  two  substances — a  solid  fibrin  and  a  soluble 
protein.  Clotting  therefore,  accordmg  to  Denis,  was  dependent  on  the  splitting 
of  a  single  protein  into  two  different  proteins,  one  of  which  was  insoluble.  A 
few  years  later  the  subject  was  taken  up  by  Alexander  Schmidt,  who  devoted  the 
remainmg  thirty  years  of  his  life  to  the  investigation  of  the  coagulation  of  the 
blood.  Working  first,  as  Buchanan  had  done,  on  fluids  obtained  from  serous 
cavities,  he  noticed  that  these  could  be  made  to  clot  by  the  addition  of  serum, 
and  he  concluded  that  coagulation  was  due  to  the  interaction  or  combination  of 
two  different  proteins,  one  fibrinogen,  contained  in  the  serous  fluid,  and  the 
other  '  fibrinoplastin,'  which  was  contained  in  the  serum  and  could  be  precipitated 
by  acidification  or  by  dilution  and  passage  of  a  stream  of  carbon  dioxide.  This 
fibrinoplastin  was  identical  with  what  we  should  nowadays  call  paraglobulin, 
but  had  adherent  to  it  fibrin  ferment.  Schmidt  later  on  found  that  in  many 
cases  it  was  not  sufficient  to  mix  these  two  substances  together,  but  that  a  third 
factor  was  necessary,  which  could  be  obtained  either  from  serum  or  from  blood- 
clot  which  had  been  coagulated  by  alcohol.  This  third  factor  he  compared  to  a 
ferment,  so  that  the  theory  put  forward  by  Schmidt  in  1872  was  that  coagulation 
depends  on  the  interaction  of  two  substances — fibrinogen  and  fibrinoplastin — 
under  the  influence  of  a  third  substance,  fibrin  ferment  or  thrombin.  A  few 
years  later  Hammarsten,  of  Upsala,  in  a  very  careful  series  of  experiments, 
proved  conclusively  that  the  fibrinoplastin  of  Schmidt  was  not  a  necessary 
factor.  Hammarsten  discovered  the  method  which  we  use  at  the  present  time 
for  separation  of  fibrinogen,  namely,  precipitation  by  half-saturation  with 
common  salt,  and  showed  that  the  fibrinogen  obtained  in  this  way  and  purified 
by  repeated  precipitation  and  re-solution  would  jield  a  clot  of  fibrin  on  the 
addition  of  fibrin  ferment  prepared  by  Schmidt's  process.  According  to 
Hammarsten,  therefore,  clotting  was  due  to  the  converson  of  the  fibrinogen 
present  in  the  circulating  plasma  into  fibrin  by  the  action  of  fibrin  ferment, 
which  was  probably  jdelded  by  the  disintegration  of  the  white  blood-corpuscles. 
Schmidt's  later  work  was  directed  chiefly  to  determining  the  mode  of  origin  of 
the  fibrin  ferment.  Though  his  researches  yielded  a  nvimber  of  important  facts, 
especially  as  to  the  part  played  by  tissue-cells  in  furnishing  the  precursors  of 
the  ferment  or  in  influencing  the  processes  of  clotting,  they  did  not  result  in 
clarifying  the  views  of  physiologists  generally  on  the  subject  of  clotting. 
Perhaps  their  most  useful  effect  was  to  demonstrate  the  complexity  of  the 
processes  which  occur  in  the  blood  after  it  leaves  the  vessels,  and  to  show  that 
in  the  maintenance  of  the  fluid  condition  in  the  vessels  as  well  as  in  the  production 
of  a  clot  outside  the  vessels  there  must  be  an  interaction  between  the  opposing 
factors,  some  of  which  hinder  and  some  of  which  favoiu"  the  occurrence  of 
coagulation.  According  to  Schmidt  the  plasma  is  itself  derived  from  the  cells 
of  the  body,  the  fibrinogen  being  formed  through  the  stages  of  paraglobulm 
and  cj^toglobulin.  The  thrombin  is  derived  from  a  precursor  prothrombin 
under  the  action  of  a  zymoplastic  substance  also  derived  from  the  cells.  In 
the  presence  of  the  proper  concentration  of  salts  the  thrombin  acts  upon 
fibrinogen  to  produce  fibrin.  His  views  may  be  roughly  expressed  by  the 
following  schema  given  by  Howell: 


THE  COAGULATION  OF  THE  BLOOD  961 

Cells 

I 
Plasma 

Cytoglobulin  Zymoplastic  Prothromljiu 

substance 


Paraglobulin 

I 
Fibrinogen 


Thrombin 


Soluble  fibrin  -  Salts  =  Fibrin 


Some  important  light  was  thrown  on  the  subject  by  the  researches  of  Wool- 
dridge.  Working  chiefly  with  peptone  plasma,  he  showed  in  the  first  place  that 
such  plasma  contained  all  the  factors  necessary  for  the  production  of  fibrin,  and 
therefore  that  the  co-operation  of  leucocytes  was  not  a  necessary  part  of  the 
process.  Peptone  plasma,  separated  entirely  from  leucocytes  and  red  corpuscles, 
could  be  made  to  clot  by  dilution,  by  the  passage  of  a  stream  of  carbon  dioxide 
or  filtration  through  a  clay  cell.  This  power  of  clotting  without  addition  of  any 
other  substances  depended  on  the  presence  in  the  plasma  of  a  substance  called 
by  Wooldridge  '  A-fibrinogen,'  which  was  throwii  down  as  a  disc-like  precipitate 
on  cooling  to  0°  C.  On  separating  this  precipitate,  which  he  regarded  as 
equivalent  to  the  blood-platelets,  by  means  of  the  centrifuge,  the  remaining 
plasma  would  only  clot  on  the  addition  of  extracts  of  tissues.  Since  neither  the 
original  plasma  nor  the  plasma  after  separation  of  the  A-fibrinogen  would  clot 
on  the  addition  of  fibrin  ferment,  Wooldridge  thought  that  the  fibrinogen  of 
Hammarsten  was  absent  from  such  plasma,  which  only  contained  two  fibrinogens, 
A-  and  B-fibrinogen.  Clotting  therefore  consisted  essentially  in  an  interaction 
between  A-  and  B-fibrinogen,  and  was  inaugurated  by  the  appearance  of 
A-fibrinogen  as  a  disc-like  precipitate.  In  this  interaction  he  showed  that 
ferment  was  produced,  and  the  weakest  part  of  his  theory  was  that  it  gave 
practically  no  office  to  the  ferment  produced  during  the  first  steps  of  the  process 
imagined  by  him.  The  B-fibrinogen  could  be  thrown  do^vn  by  the  action  of 
dilute  acid  or  of  salt  from  the  plasma  after  separation  of  the  A-fibrinogen.  After 
precipitation  and  re-solution  two  or  three  times  it  would  clot  •ndth  fibrin  ferment, 
and  was  coagulated  at  a  temperature  of  56°  C,  and  was  therefore  the  typical 
fibrinogen  of  Hammarsten.  According  to  Wooldridge,  therefore,  previous 
observers  had  been  workmg,  not  with  the  fibrinogens  of  the  plasma,  but  with  a 
fibrinogen  altered  by  repeated  precipitation  and  re-solution.  One  fact  dis- 
covered by  him  which  at  once  attained  universal  recognition  was  the  production 
of  intravascular  clotting  by  the  injection  of  tissue  extracts.  These  tissue 
extracts  contained  tissue  fibrinogens  which  he  compared  with  A-fibrinogen. 
According  to  him  clotting  could  be  inaugiu-ated  either  by  the  action  of  A-fibri- 
nogen on  the  B-fibrinogen,  or  by  the  action  of  tissue  fibrinogen  on  the  B-fibri- 
nogen of  the  plasma.  In  every  case  fibrin  ferment  resulted  and  could  therefore 
efifect  the  conversion  of  any  C-fibrinogen  of  Hammarsten  which  might  bo  present 
in  the  fibrin.  It  will  be  seen  that  this  theory  of  Wooldridge  presents  a  striking 
similarity  to  that  which  is  generally  accepted  at  the  present  day.  If  Ave  change 
the  names  of  A-fibrhiogen  to  thrombokmase,  of  B-fibrinogen  to  thrombogen, 
we  see  that  the  only  difference  between  Wooldridgc's  theory  and  that  of 
Morawitz  is  that  the  former  ignored  the  importance  of  lime  salts  in  the  proceae 
and  imagined  that  the  interaction  of  thrombokinaso  and  thrombogen  resulted 
in  the  direct  production  of  fibrin  iis  well  as  ferment,  instead  of  recognising  that 

61 


962  PHYSIOLOGY 

the  interaction  of  the  two  substances  was  simph*  a  first  stage  and  that  thrombin 
was  formed  in  this  process  for  the  subsequent  conversion  of  the  fibrinogen  into 
fibrin. 

Attention,  however,  was  largely  diverted  from  Wooldridge's  work  by  the 
discovery  of  the  necessity  of  calcium  salts  for  clotting.  Green  had  already 
sho\ni  that  the  clotting  of  many  forms  of  salt  plasma  could  be  hastened  by  the 
addition  of  calcium  sulphate,  whereas  the  coagulation  of  serous  fluids  was  not 
affected  by  this  salt.  Green  suggested  that  possibly  a  zymogen  of  the  ferment 
was  activated  by  the  calcixun  salt.  The  absolute  necessity  of  the  presence  of 
this  salt  was  first  demonstrated  by  Arthus  and  Pages  (1890)  on  oxalate  and 
fluoride  plasma.  At  first  Arthus  was  inclined  to  regard  the  part  played  by 
calcium  salts  m  the  coagulation  of  the  blood  as  analogous  in  all  respects  to  that 
played  ra  the  coagulation  of  milk  by  rennet,  and  suggested  that  the  conversion  of 
fibrmogen  into  fibrm  was  actually  the  combination  of  fibrinogen  vrith  calcium 
salts,  the  combination  bemg  effected  by  the  agencj'  of  the  ferment.  It  was  shoMTi, 
however,  by  Pekelharing  that  the  power  of  lime  salts  to  produce  clotting  in 
oxalate  plasma  was  annulled  if  the  body  precipitable  by  cold  had  been  previously 
removed,  and  Hammarsten  proved  conclusively  that  the  action  of  calcium 
salts  was  on  this  prothrombin  and  not  on  the  fibrinogen,  careful  analyses  of 
fibrinogen  and  fibrin  respectively  giving  practicaUy  equal  figures  for  calcium. 
Hammarsten  pointed  out  moreover  that  fibrin  ferment  would  convert  fibrinogen 
into  fibrin  in  the  total  absence  of  soluble  calcium  salts  and  even  in  the  presence 
of  a  slight  excess  of  oxalate. 

Later  experiments  have  had  reference  chiefly  to  the  nature  of  the  pro- 
thrombm  precipitate  and  to  the  question  of  the  origin  of  the  fibrin  ferment  from 
the  blood-plasma.  Recent  advances  in  the  subject  were  much  facilitated  by 
the  discovery  by  Delezenne  that  birds'  blood  could  be  prevented  from  clotting 
by  the  simple  expedient  of  collecting  it  free  from  any  contact  wth  the  tissues. 
A  careful  study  of  this  blood  and  a  comparison  of  its  behaviour  with  that  of 
other  forms  of  uncoagulable  plasma  by  Fuld  and  Spiro,  and  especially  by 
Morawtz,  have  resulted  in  the  further  separation  of  the  precursor  of  fibrin  into 
two  substances,  thrombokinase  and  thrombogen.  Further  investigations  by 
Xolf  have  dealt  especially  ■with  the  question  of  the  interaction  which  is  con- 
tinually taking  place  between  the  vessel  wall  and  the  contained  blood,  and  which 
may  result,  according  to  the  circumstances,  in  the  diminution  or  increase  in  the 
coagulability  of  the  blood.  According  to  Xolf  the  essential  factors  in  the  pro- 
duction of  blood-clotting  are  tliree  protems,  namely,  fibrinogen,  thrombogen, 
and  thrombozjTn.  The  two  former  are  produced  in  the  liver,  Avhile  the  throm- 
bozym  is  formed  from  the  leucocj-tes.  The  clotting  depends,  not  on  a  ferment 
action,  but  on  a  mutual  interaction  and  precipitation  of  colloids  with,  as  a  result, 
either  fibrin  or  thrombin.  Thrombin  differs  from  fibrin  merely  in  containing 
less  fibrinogen.  For  this  reaction  to  take  place  the  presence  of  calcium  is 
necessary  as  well  as  certain  thromboplastic  substances  which  act  as  centres  of 
precipitation.  The  fluid  condition  of  the  blood  in  the  vessels  depends  on  the 
presence  of  an  antithrombin  formed  in  the  liver.  Nolf  thus  agrees  -with  Wool- 
dridge  in  regarding  thrombin  as  a  product  of  coagulation  rather  than  a  cause. 
Thrombin,  according  to  him,  is  merely  an  unsaturated  compoimd  which  is 
capable  of  taking  up  or  imiting  with  more  fibrinogen  to  form  fibrin.  Nolf  would 
regard  the  formation  of  fibrin  as  an  important  preparatorj'  step  in  the  nutrition 
of  the  cells.  He  compares  these  actions  occiuring  in  the  blood  to  the  actions 
of  digestive  ferments  on  proteins.  Just  as  casein  is  first  precipitated  and  then 
digested  by  pepsin,  so  fibrinogen  is  first  precipitated  as  fibrin  by  union  with 
thrombozjTn  and  thrombogen.  This  fibrin  is  then  hydrolysed  and  dissolved  by 
the  further  action  of  the  thrombozym,  which  he  regards  as  essentially  proteolytic 


THE   COAGULATION   OF  THE  BLOOD  963 

in  character.  That  the  whole  blood  does  not  coagulate  within  the  vessels  he 
explains  by  assuming  that  the  cells  of  the  blood  and  tissues  are  covered  normally 
with  an  ultra-microscopic  lajer  of  fibrin.  This  forms  a  neutral  siu^ace,  like  a 
parafl&ned  vessel,  which  has  no  thromboplastic  effect  upon  the  plasma. 

According  to  Mellanby  the  prothrombin  in  the  plasma  is  constantly  associated 
with  the  fibrinogen.  It  may  be  converted  to  thrombin  either  by  the  action  of 
calcium  and  thrombokinase,  or  by  the  action  of  calcium  and  alkali,  or  possibly 
by  the  action  of  calcium  alone.  The  latest  work  on  the  subject  by  Rettger  has 
tended  somewhat  to  the  simplification  of  this  extremely  complex  problem.  In 
the  first  place,  he  regards  the  formation  of  fibrin  as  non-fermentative  In  character, 
thus  agreeing  with  Xolf,  fibrin  being  produced  by  the  simple  imion  of  fibrinogen 
and  thrombin.  He  finds  no  evidence  of  the  pre-existence  in  the  blood  of  a 
thrombin  or  pro-ferment,  and  is  inclined  to  regard  the  action  of  so-called  kinases, 
which  can  be  extracted  from  animal  tissues,  as  similar  to  that  of  such  agents  as 
dust,  threads  of  linen,  which  can  produce  a  similar  coagulating  effect  in  birds' 
blood.  The  thrombin  he  regards  as  derived  from  the  formed  elements  at  the 
moment  of  their  rapid  disintegration  when  placed  imder  abnormal  circumstances. 
For  the  formation  of  active  thrombin  a  minimal  amount  of  calcium  salts  must 
enter  into  the  molecular  complex.  We  thvis  return  to  the  simpler  expression 
of  the  processes  of  coagulation  as  given  by  Pekelharing  and  Hammarsten,  the 
prothrombin  which  is  formed  from  the  platelets  and  leucocytes  by  secretion  or 
process  of  disintegration  being  activated  to  thrombin  by  the  calcium  salts 
present,  and  the  thrombin  so  formed  combining  quantitatively  ^^ith  the  fibrinogen 
to  form  fibrin.  The  prothrombin  is  not  readily  destroyed.  It  may  remain  in 
calcium-free  serum  for  days  and  when  activated  form  thrombin  quickly. 
Thrombin,  on  the  other  hand,  disappears  very  rapidly  from  active  serum  in 
consequence  of  combining  -with  some  of  the  proteins  of  the  serum.  This  property 
of  combining  -with  the  fibrinogen  and  disappearing  from  the  serum  is  not  shared 
by  the  prothrombin. 


SECTION  V 

THE  QUANTITY  AND  COMPOSITION  OF  THE 
BLOOD  IN  MAN 

A.  THE  TOTAL  QUANTITY  OF  BLOOD  IN 
THE  BODY 
The  amount  of  blood  contained  in  the  body  can  be  estimated  by 
Welcker's  method.  It  is  not  sufhcient  simply  to  open  one  of  the 
blood-vessels  and  allow  the  animal  to  bleed  to  death,  because  it  is  not 
possible  in  this  way  to  obtain  the  whole  of  the  blood  present  in  the 
body,  and  the  blood  which  is  obtained  gradually  becomes  more  dilute 
in  consequence  of  absorption  from  the  tissue  spaces  as  bleeding  con- 
tinues. A  small  sample  of  blood  is  therefore  taken  from  a  blood- 
vessel and  diluted  100  times  with,  distilled  water  to  serve  as  a  standard 
of  comparison.  The  animal  is  then  bled  from  a  cannula  placed  in  a  large 
artery,  while  at  the  same  time  normal  salt  solution  is  led  into  a  vein 
so  as  to  maintain  the  vascular  system  as  full  as  possible  and  allow  of  its 
being  washed  out  by  the  action  of  the  heart.  When  the  heart  ceases 
to  beat,  the  blood-vessels  are  thoroughly  washed  out  by  a  stream  of 
normal  salt  solution  from  the  aorta.  The  animal  is  then  minced  up 
thoroughly  and  extracted  with  distilled  water  and  filtered  so  as  to 
dissolve  out  the  haemoglobin  still  adherent  to  the  tissues  and  especially 
contained  in  the  red  marrow.  These  washings  are  mixed  •«ath  the 
whole  diluted  blood  and  the  strength  of  the  mixture  in  haemoglobin  is 
compared  with  that  of  the  standard  solution.  In  this  way  it  is  possible 
to  estimate  the  total  haemoglobin  present  in  the  body  in  terms  of  the 
sample  and  so  find  the  total  amount  of  circulating  fluid.  It  has  been 
found  that  the  dog  contains  about  7-7  per  cent,  of  his  body  weight  as 
circulating  blood,  and  although  smaller  figures  were  obtained  on 
other  animals,  such  as  the  rabbit,  the  number  of  one-thirteenth  has 
been  taken  as  appUcable  to  man  on  the  basis  of  two  observations  made 
long  ago  on  executed  criminals.  Haldane  has  shoA\ii  recently  that 
this  estimate  is  much  too  high,  the  average  amount  of  blood  in  man 
being  only  about  4-9  per  cent,  of  the  body  weight,  i.e.  about  one- 
twentieth  ;  in  some  cases,  as  in  fat  individuals,  it  may  be  as  Uttle  as  one- 
thirtieth.  Since  the  determination  of  the  total  volume  of  the  circu- 
lating blood  plays  an  important  part  in  the  consideration  of  the 
pathology  of  certain  diseases  such  as  anaemia  and  heart  disease,  the 

964 


QUANTITY  AND  COMPOSITION  OF  BLOOD  965 

ingenious  method  adopted  by  Haldane  for  this  determination  in 
the  living  animal  may  be  here  described.  The  method  depends  on  the 
fact  that  carbon  monoxide  gas  when  inhaled  combines  with  haemo- 
globin, expelling  the  oxygen  from  the  oxyhajmoglobin.  If  therefore 
we  allow  a  man  to  breathe  a  certain  volume  of  carbon  monoxide 
until  it  is  entirely  absorbed  and  then  find  that  one-fifth  of  the  haemo- 
globin in  his  blood  is  saturated  'vvath  carbon  monoxide,  we  know  that 
the  whole  blood  could  take  up  five  times  the  bulk  of  carbon  monoxide 
which  the  man  has  inspired.  We  therefore  in  this  way  determine 
the  total  '  carbonic  oxide  capacity  '  of  the  blood,  and  since  CO- 
hsemoglobin  contains  the  same  volume  of  carbon  monoxide  as  oxy- 


Fio.  .365.     Haldane's  CO  method  for  determining  total  blood  volume  in  man. 

haemoglobin  does  of  oxygen,  the  same  figure  gives  us  the  total '  oxygen 
capacity.'  The  total  oxygen  capacity  enables  us  to  determine  the 
total  amount  of  haemoglobin  in  the  body,  and  if  we  know  the  per- 
centage amount  of  haemoglobin  in  the  blood  it  is  easy  to  calculate 
the  total  volume  of  circulating  fluid. 

Before  the  carbonic  oxide  is  administered  the  pcrcontape  oxygen  capacity,  i.e. 
the  volume  of  oxygen  capable  of  being  taken  up  by  the  haimoglobm  of  1CM1  c.c, 
of  the  blood,  is  determined  as  follows  :  The  oxygen  capacity  of  a  sample  of 
fresh  ox  blood  is  accurately  determined  by  the  ferricyanide  method  {v.  p.  969). 
The  ox  blood  is  then  compared  colorimetrically  with  blood  obtained  in  the 
ordinary  way  by  means  of  a  ha;moglobinometer  needle  from  the  finger  of  the 
subject  of  the  experiment,  and  the  oxygen  capacity  of  the  latter  blood  calculated 
from  the  result  of  the  comparison.  Tlie  subject  is  now  matlo  to  breathe  through 
a  mouthpiece  a  (Fig.  305)  into  a  Uladder  b  of  about  2  litres  capacity.  The 
carbon  dioxide  produced  during  the  experiment  is  absorbed  by  the  soda  lime  vessel 
between  the  mouthpiece  and  the  bladder.     The  oxygen  as  it  is  used  up  is  replaced 


966 


PHYSIOLOGY 


from  an  oxygen  cylinder  through  the  tube  c.  d  is  a  graduated  vessel  containing 
pure  carbonic  oxide  gas.  Wliile  the  subject  is  breathing  in  and  out  of  the  bag 
a  given  volume  of  carbon  monoxide  is  admitted  into  the  bag,  being  driven  out 
from  the  tube  d  by  allowing  water  to  flow  through  the  tap  e.  The  required 
volume  of  carbon  monoxide  is  gradually  driven  in  from  the  measuring  cylinder 
at  the  rate  of  about  30  c.c.  every  two  minutes.  When  the  required  quantity 
has  been  driven  in  and  pushed  forward  by  the  oxygen  an  interval  of  two  or 
three  minutes  is  allowed  to  elapse.  After  this  a  drop  of  blood  is  taken  for 
analysis.  It  contains  a  certain  amount  of  CO-haemoglobin.  The  relative 
saturation  of  the  blood  in  carbon  monoxide  is  determined  by  the  colorimetric 
method.  A  number  of  narrow  test-tubes  of  exactly  equal  diameter  and  each 
holding  about  6  c.c.  are  taken,  and  2  c.c.  of  water  saturated  Mnth  air  meas\u-ed 
off  into  each.  Two  cubic  millimetres  of  the  blood  of  the  svibject  are  measured 
off  in  the  ordinary  waj^  by  means  of  a  hsemoglobinometer  pipette  into  each  of  the 
six  tubes,  the  solutions  being  well  mixed.  Four  cubic  millimetres  of  this  blood  are 
thoroughly  saturated  with  coal  gas  and  placed  in  another  shorter  tube,  which  is 
filled  full  and  tightly  corked.  In  this  tube  the  haemoglobin  is  completely  saturated 
with  carbon  monoxide.  After  the  subject  has  breathed  the  carbon  monoxide,  a 
sample  of  his  blood  is  taken  and  diluted  as  before.  The  solution  in  this  tube  is, 
of  course,  pinker  than  those  in  the  other  tubes.  A  standard  solution  of  carmine 
is  now  added  from  a  narrow  biu-ette  to  one  of  the  tubes  of  normal  blood  solution 
until  its  tint  is  the  same  as  that  of  the  blood  taken  after  the  inhalation.  Addition 
of  the  carmine  is  then  continued  until  the  tint  is  equal  to  that  of  the  blood 
Bolution  which  is  entirely  saturated  with  carbon  monoxide.  Supposing  that 
0-45  c.c.  of  carmine  was  required  to  produce  equality  of  tint  -with,  that  of  the 
blood  taken  during  the  experiment  and  2-5  c.c.  to  produce  equality  of  tint  with 
that  of  the  sattu-ated  blood,  then  as  2-5  c.c.  of  carmme  in  4-5  c.c.  of  liquid  were 
required  to  produce  satiu^ation  tint,  and  only  0-45c.c.  of  carmine  in  2-45  c.c.  of 
liquid  to  produce  the  tint  of  the  blood  mider  examination,  the  percentage 
saturation  of  the  latter  could  be  calculated  by  the  following  sum  : 


2^ 
4-5 

X  •= 


•45 
*  245 
33-1 


100 


Although  this  method  requires  careful  execution  in  order  to  avoid 
fallacies,  it  is  possible  to  attain  results,  as  has  been  shown  by  Douglas, 
closely  agreeing  with  Welcker's  method.  The  error  is  probably  not 
greater  than  10  per  cent.,  which  is  negligible  in  comparison  with  the 
large  changes  in  total  blood  volume  which  have  been  found  to  occur 
in  certain  cases  of  disease.  The  total  record  of  two  such  observations 
by  Haldane  and  Lorrain  Smith  may  be  here  quoted  : 


Normal  lNDi\aDUAL 


Body  weight 

in 
kilogrammes 

Volume  of  dry  CO. 

absorbed  in  c.c. 

at  0'  C. 

Percentage 
saturation  of 
[Hg  with  CO. 

Dry  oxygen 
capacity  of 
blood  in  c.c. 

72-9 

116 

18-9 

614 

89-0 

116 

22-7 

511 

Oxygen  capacity 
per  100  c.c.  of 
blood  in  c.c. 

Total  amount 

of  blood 
in  grammes 

Grammes  of  blood 
per  100  grm.  of 
body  weight. 

c.c.  of  oxygen 
per  100  grm. 
body  weight. 

18-7 

3455 

4-75 

0-84 

18  2 

2970 

3-34 

0-57 

QUANTITY  AXD  COMPOSITION  OF  BLOOD  967 

In  applying  this  method  in  cases  of  disease  it  is  important  not  to  give 
too  large  a  dose  of  carbonic  oxide  gas.  In  a  normal  individual  30  per 
cent,  of  the  haemoglobin  may  be  combined  xsnth  carbon  monoxide 
before  any  oxygen  hunger  is  felt,  and  it  is  possible  to  saturate  half  the 
haemoglobin  with  this  gas,  though  \Nnth  considerable  discomfort  to  the 
individual.  In  cases  such  as  heart  disease,  where  the  patient  is  at 
the  very  margin  of  his  resources,  even  .30  per  cent,  diminution  of  the 
oxygen  capacity  of  the  blood  may  have  serious  results,  and  the  carbon 
monoxide  inspired  must  be  therefore  kept  at  the  lowest  limit  at  which 
it  is  possible  to  carry  out  a  reliable  determination  of  the  relative 
carbonic  oxide  saturation  of  the  blood  sample. 

The  total  blood  volume  probably  varies  appreciably  with  altera- 
tions in  the  conditions  of  the  animal,  and  may  be  found  different  on 
two  succeeding  days.  It  is  certainly  influenced  by  the  height  of  the 
blood  pressure  as  well  as  by  the  oxygen  tension  in  the  air  breathed,  and 
therefore  alters  with  the  altitude.  Some  of  these  variations  we  shall 
have  to  consider  more  fully  in  a  later  section.  Any  lowering  of  blood 
pressure  causes  an  absorption  of  fluid  from  the  tissues  into  the  blood, 
so  that  the  latter  becomes  more  dilute.  The  blood  content  during 
the  last  stages  of  bleeding  may  contain  little  more  than  50  or  60  per 
cent,  of  the  haemoglobin  which  was  present  in  the  first  samples  of  blood, 
pointing  to  a  corresponding  dilution  of  the  blood  during  these  few 
minutes  by  means  of  tissue  IjTnph.  By  this  means,  i.e.  the  absorption 
of  fluid  from  tissues,  the  volume  of  circulating  blood  after  a  hniited 
haemorrhage  is  rapidly  brought  up  to  normal,  so  that  there  is  a  circula- 
tion of  a  fluid  impoverished  in  corpuscles.  The  latter  are  made  up 
in  the  course  of  a  few  weeks  as  a  result  of  increased  activity  in  the 
bone-marrow. 


RELATIVE  AMOUNT  OF  PLASMA  AND  CORPUSCLES 
The  relative  anKnint  of  corpuscles  in  a  given  sample  of  blood  is 
most  easily  determined  by  Blix's  method.  The  blood  is  mixed  with 
a  definite  amount  of  2|-  potassium  bichromate,  and  the  mixture  is  put 
into  small  graduated  capillary  tubes,  which  are  then  placed  in  a  cen- 
trifuge revolving  about  I0.0<X)  times  per  minute.  The  corpuscles 
rapidly  accumulate  in  an  almost  solid  mass  at  the  bottom  of  the  tube, 
and  their  volume  can  be  directly  read  off.  It  is  often  possible  by  work- 
ing quickly  to  receive  blood  into  such'  graduated  capillary  tubes  and 
to  centrifuge  it  rapidly  before  it  has  had  time  to  coagiilate.  The 
corpuscles  are  hurried  down  to  the  bottom  of  the  tube  within  two  or 
three  minutes  and  their  volume  can  be  in  this  way  directly  determined. 
An  indirect  method  for  the  same  purpose  was  devised  by  Hoppe- 
Seyler.  The  total  proteins  of  defibrinated  blood  are  determined  and 
compared  with  the  total  proteins  of  the  washed  corpuscles  and  of 


968  PHYSIOLOGY 

the  Beruin.  Thus  in  one  experiment  100  grm.  of  defibrinated  pigs' 
blood  contained  18-90  grm.  protein  pliis  hsemoglobin.  The  blood- 
corpuscles  of  100  grm.  of  the  same  blood  contained  15*07  grm.  pro- 
teins phis  haemoglobin  ;  therefore  the  serum  of  the  same  100  grm.  of 
blood  contained  18-90— 1507  =  3-83  grm.  proteins.  One  hundred 
grammes  of  serum  contain  6*77  grm.  protein.  From  these  figures  the 
amount  of  serum  in  the  100  grm.  of  defibrinated  blood  may  be  com- 
puted as  follows  : 

3-83 

100  =  56-6  per  cent,  serum. 

6-77  ^ 

100—56-6  =  43-4  per  cent,  blood-corpuscles. 

The  average  volume  of  corpuscles  in  human  blood  can  be  taken  as 
50  per  cent,  of  the  total  amount,  different  estimations  having  given 
figures  varying  from  48  to  54  per  cent.  In  the  horse  the  volume  of 
corpuscles  is  53  per  cent.,  in  the  dog  36  per  cent. 

THE  ENUMERATION  OF  THE  CORPUSCLES 
In  order  to  enumerate  the  red  corpuscles  the  blood  is  diluted  with 
a  known  amount  of  an  isotonic  fluid  and  the  number  is  counted  in  a 
measured  volume  of  the  mixture.  The  average  number  of  red  cor- 
puscles is  about  5,000,000  per  cubic  millimetre  in  adult  men  and  rather 
fewer,  about  4,500,000,  in  adult  women.  The  enumeration  of  cor- 
puscles is  subject  to  considerable  errors,  probably  not  less  than  10  per 
cent.  Moreover  difierent  conditions  of  the  circulation  may  cause 
variations  in  the  relative  distribution  of  plasma  and  corpuscles 
respectively  in  different  parts  of  the  circulation,  so  that  the  blood-count 
of  a  specimen  from  the  capillaries  of  the  finger  or  lobe  of  the  ear  may 
vary  considerably  from  a  similar  count  of  the  corpuscles  in  blood 
obtained  directly  from  a  minute  vein  or  artery.  More  important 
therefore  is  the  determination  of  the  haemoglobin.  For  this  purpose 
a  measured  quantity  of  the  blood,  2  to  5  c.mm.,  is  obtained  in  a 
capillary  pipette  and  mixed  \\ith  a  given  volume  of  water.  The  red 
fluid  thus  obtained  is  compared  with  a  standard.  This  latter  in  von 
Fleischl's  instrument  is  a  prism  of  coloured  glass.  In  Oliver's 
instrument  the  standard  consists  of  a  series  of  tinted  glasses,  one  of 
which  represents  the  colour  of  a  measured  quantity  of  normal  blood 
diluted  with  water  and  placed  in  a  flat  glass  cell  of  a  certain  size,  while 
the  others  represent  percentages  of  haemoglobin  below  and  above  the 
normal.  The  most  accurate  method  is  that  due  to  Hoppe-Seyler  and 
Haldane,  namely,  the  conversion  of  the  blood  sample  into  CO-haemo- 
globin'and  its  comparison  xs-ith  a  standard  specimen  of  CO-haemoglobin, 
which  is  stable  in  solution  and  can  therefore  be  kept  in  a  sealed  glass 
vessel  for  any  length  of  time. 


QUANTITY  AND  rOMPOSITION  OF  BLOOD 


969 


THE  OXYGEN  CAPACITY  OF  THE  BLOOD 
Instead  of  determining  the  hsemoglobin  we  may  measure  directly 
the  oxygen  capacity  of  the  blood,  since  the  oxygen-binding  power  of 
this  fluid  is  entirely  dependent  on  the  amount  of  haemoglobin  it 
contains.  For  this  purpose  we  may  make  use  of  the  fact  discovered 
by  Haldane,  that  the  combined  oxygen  in  oxyhaemoglobin  is  liberated 
rapidly  and  completely  on  addition  of  a  solution  of  potassium  ferri- 
cyanide  to  laked  blood,  and  may  thus  be  easily  measured  with  the  help 
of  an  apparatus  similar  to  that  used  for  determining  urea  in  urine  by  the 
hypobromite  method. 


Fig.  366. 


Haldane's  method  for  determining  the  oxygen  capacity 
of  the  blood. 


The  following  description  of  the  method  is  given  by  Haldane  : 
"  Twenty  cubic  centimetres  of  theoxalatcdor  defibrinated  blood,  thoroughly 
saturated  with  air  by  swinging  it  round  in  a  large  flask,  are  measiu-ed  out  from  a 
pipette  into  the  bottle  a,  which  has  a  capacity  of  about  120  c.c.  As  it  is  important 
to  avoid  blowing  expired  air  into  the  bottle  the  last  drops  of  blood  are  expelled 
from  Iho  pipette  by  closing  the  top  and  wanning  the  bulb  with  the  hand."  Thirty 
cubic  centimetres  are  then  added  of  a  solution  prepared  by  diluting  ordinary  strong 
ammonia  solution  (sp,  gr.  0-88)  wth  distilled  water  to  ^^,^.  The  ammonia  pre- 
vents carbonic  acid  from  coming  off,  while  the  distilled  water  lakes  the  corpuscles. 
The  blood  and  ammonia  solution  are  thoroughly  mixed  by  shaking,  and  at  the  end 
of  this  operation  the  solution  should  appear  perfectly  transparent  when  tilted  up 
against  the  sides  of  the  bottle.*     About  4  c.c.  of  a  saturated  solution  of  potassium 

*  If  the  solution  were  not  transparent  this  would  indicate  that  the  laking 
was  incomplete,  and  more  ammonia  solution  would  need  to  be  added. 


970  PHYSIOLOGY 

ferricyanide  are  then  poured  into  the  small  tube  b  (the  length  of  which  should 
slightly  exceed  the  width  of  the  bottle)  and  placed  upright  in  A.  The  rubber 
stopper,  which  is  provided,  as  shown,  with  a  bent  glass  tube  connected  with  the 
burette  by  stout  rubber  tubing  of  about  1  mm.  bore,  is  then  firmly  put  in,  and 
the  bottle  placed  in  the  vessel  of  water  c,  the  temperature  of  which  should  be  as 
nearly  as  possible  that  of  the  room  and  of  the  blood  and  water  in  the  bottle.  If 
the  stopper  is  not  heavy  enough  to  sink  the  bottle  the  latter  should  be  weighted. 
By  opening  to  the  outside  the  three-way  tap  (or  T-tube  and  clip)  on  the  burette, 
and  raising  the  levelling  tube,  which  is  held  by  a  spring  clamp,  the  water  in  the 
burette  is  brought  to  a  level  close  to  the  top.  The  tap  is  then  closed  to  the 
outside,  and  the  reading  of  the  burette  (which  is  graduated  to  -05  c.c,  and  may 
be  read  to  -01  c.c.)  taken  after  careful  levelling. 

The  water-gauge  (which  has  a  bore  of  about  1  mm.)  attached  to  the  tempera- 
ture and  pressure- control  tube  is  now  accurately  adjusted  to  a  definite  mark. 
This  is  easily  accomplished  by  sliding  the  rubber  tube  backwards  or  forwards 
on  the  piece  of  glass  tubing  d.  The  control  tube  is  an  ordinary  test-tube 
containing  some  mercury  to  sink  it,  and  connected  with  the  gauge  by  stout 
rubber  tubing  of  about  1  mm.  bore. 

As  soon  as  the  reading  of  the  burette  is  constant,  which  it  will  probably  be 
within  two  or  three  minutes,  the  bottle  is  tilted  so  as  to  upset  b,  and  is  shaken  as 
long  as  gas  is  evolved.  Dvu-ing  this  operation  b  should  be  repeatedly  emptied, 
as  otherwise  the  oxygen  dissolved  in  its  liquid  might  not  be  completely  given 
off.  When  the  evolution  of  oxygen  has  ceased  the  bottle  is  replaced  in  the 
water.  If,  as  is  probable,  the  pressure-gauge  indicates  an  alteration  in  the 
temperature  of  the  water,  cold  water  from  the  tap,  or  warmed  water,  is  added 
till  the  original  temperature  has  been  re-established,  and  the  reading  of  the 
burette  noted  as  soon  as  it  is  constant.  The  bottle  is  again  shaken,  &c.,  until 
a  constant  residt  is  obtained,  for  which  about  fifteen  minutes  from  the  beginning  of 
the  operations  are  required.  The  temperature  of  the  water  in  the  jacket  of  the 
burette,  and  the  reading  of  the  barometer,  are  now  taken,  and  the  gas  evolved 
is  reduced  to  its  dry  volume  at  0°  and  760  mm.  To  calculate  the  oxygen  evolved 
from  100  c.c.  of  blood,  allowance  must  be  made  for  the  fact  that  a  20  c.c.  pipette 
does  not  deliver  20  c.c.  of  blood,  but  only  about  19-6  c.c.  The  actual  amount 
of  shortage  for  a  given  pipette  can  easily  be  determined  by  weighing  the  pipette 
after  water,  and  again  after  blood,  has  been  delivered  from  it.  A  further  slight 
correction  is  necessary  on  account  of  the  fact  that  the  air  in  the  bottle  at  the  end 
of  the  operation  is  richer  in  oxygen  than  at  the  beginning,  so  that,  as  oxygen  is 
about  twice  as  soluble  as  nitrogen,  slightly  more  gas  will  be  in  solution.  With 
a  bottle  of  120  c.c.  capacity,  and  20  per  cent,  of  oxygen  in  the  blood,  the  air  in 
the  bottle  at  the  end  will  evidently  contain  about  27  per  cent,  of  oxygen,  so  that, 
assuming  that  the  coefficients  of  absorption' of  oxygen  and  nitrogen  in  the  54  c.c. 
of  liquid  within  the  bottle  are  nearly  the  same  as  in  water,  the  correction  will 
amount  at  15^  C-  to  -06  c.c.  in  the  reading  of  the  burette,  or  -i-  0-30  per  cent,  in 
the  result." 

THE  SPECIFIC  GRAVITY  OF  THE  BLOOD 
The  specific  gravity  of  the  blood  may  be  determined  by  directly 
weighing  a  sample,  or  more  conveniently  by  collecting  blood  in  a 
capillary  tube  and  discharging  drops  of  it  into  a  series  of  vessels  con- 
taining glycerin  and  water  mixed  in  varying  proportions.  When  it 
is  found  that  the  drop  of  blood  as  it  leaves  the  capillary  vessel  neither 
rises  nor  falls  in  the  glycerin  and  water  mixture,  we  know  that  the 
specific  gravity  of  the  blood  is  identical  with  that  of  the  mixture.     A 


QUANTITY  AND  COMPOSITION  OF  BLOOD  971 

graduated  series  of  these  mixtures  is  kept  in  bottles  and  their  specific 
gravity  is  generally  determined  before  the  experiment.  Hammer- 
schlag's  method  consists  in  placing  a  drop  of  blood  in  a  mixture  of 
chloroform  and  benzene  and  then  adding  chloroform  or  benzene,  as 
the  case  may  be,  until  the  drop  neither  rises  nor  faUs.  The  specific 
gravity  of  the  mixture  is  then  taken.  The  specific  gravity  varies 
in  man  between  1057  and  1066,  and  in  woman  from  1054  to  1061.  It 
is  increased  by  loss  of  water,  as  after  profuse  perspiration,  or  by  passive 
congestion  of  the  part  from  which  the  sample  is  taken.  It  is  also 
increased  as  a  result  of  any  operation  upon  a  serous  cavity  in  con- 
sequence of  exudation  of  plasma  in  the  inflamed  or  irritated  part.  It 
is  diminished  as  the  result  of  bleeding.  The  specific  gravity  of  serum 
is  ID28  to  10.32,  of  corpuscles  about  1090.  It  is  interesting  to  note 
that  the  specific  gravity  of  the  blood  is  highest  in  the  foetus  at  full 
term,  when  it  amounts  to  1066,  contrasting  with  that  of  the  mother 
at  the  same  time,  the  specific  gravity  of  whose  blood  is  only  1050. 
The  specific  gravity  rapidly  falls  to  the  latter  figure  after  birth. 

THE  REACTION  OF  THE   BLOOD 

The  blood  is  alkaline  to  litmus.  This  fact  can  be  demonstrated 
by  allo^ving  a  drop  to  fall  on  a  piece  of  glazed  litmus  paper  and  then 
wiping  away  the  blood  with  a  piece  of  linen  moistened  with  distiUed 
water  or  neutral  saline  solution.  In  order  to  estimate  the  alkalinity 
a  small  definite  quantity  of  the  blood  is  mixed  with  sulphate  of  soda 
solution  containing  a  definite  amount  of  tartaric  acid.  The  acid 
mixture  is  then  titrated  against  a  decinormal  solution  of  sodium 
hydrate  until  the  mixture  gives  a  blue  stain  when  a  drop  of  it  is  placed 
on  glazed  Litmus  paper.  The  alkalinity  of  normal  blood  as  deter- 
mined in  this  way  amounts  on  the  average  to  0-2  grm.  NaHO  per 
ICX)  c.c.  of  blood.  If  the  blood  be  laked  the  alkalinity  rises  to  as  much 
as  04  grm.  NaHO  per  10<J  c.c. 

All  these  questions  of  reaction  depend,  however,  on  the  indicator 
employed.  A  neutral  salt  might  react  alkaline  to  litmus  if  the  acid 
radical  of  the  salt  were  capable  of  being  displaced  by  the  coloured 
acid  radical  of  the  indicator  with  the  production  of  a  blue  alkaline 
salt  of  litmus.  Sodium  bicarbonate  may  be  acid  or  neutral  to 
litmus  and  alkaline  to  methyl  orange.  The  absolute  alkalinity  of 
any  fluid  may  be  expressed  by  the  number  of  free  OH  ions 
which  it  contains,  just  as  the  acidity  is  a  measure  of  the  free  H 
ions.  The  number  of  free  OH  ions  in  the  blood  can  be  determined  by 
an  electrical  method,  and  is  found  to  be  very  small,  very  little  more  in 
fact  than  that  contained  in  distilled  water.  The  alkalinity  of  the  blood 
as  ordinarily  determined  by  the  litmus  method  gives  us,  however,  more 
important  knowledge  than  this  determination  of  its  absolute  alkalinity, 


972  PHYSIOLOGY 

since  on  its  relative  alkalinity  to  litmus  depends  to  a  large  extent  its 
power  of  combining  with  carbon  dioxide  and  therefore  acting  as  a 
carrier  of  this  gas  from  the  tissues  to  the  lungs. 

THE  OSMOTIC  PRESSURE  OF  THE  BLOOD 
Since  the  blood  serves  as  a  circulating  medium  by  means  of  which 
the  composition  of  the  tissue  juices  forming  the  immediate  environ- 
ment of  all  the  cells  of  the  body  is  maintained  constant,  its  osmotic 
pressure  must  be  of  considerable  importance  in  regulating  the  nor- 
mal exchanges  of  the  cells  mth  their  surrounding  fluid.  The  osmotic 
pressure  of  the  blood  depends  on  its  molecular  concentration  and  can 
be  determined  by  any  of  the  methods  mentioned  earlier  (p.  140). 
Of  these  the  most  convenient  is  the  determination  of  the  freezing-point. 
The  depression  of  freezing-point,  A,  of  mammalian  blood  is  about  0-56 
and  varies  between  0-54  and  0-60.  The  depression  of  the  freezing-point 
observed  in  blood  is  equal  to  that  of  a  0-9  per  cent,  sodium  chloride 
solution,  which  is  therefore  taken  as  isotonic  with  the  blood.  Since 
the  corpuscles  are  in  osmotic  equilibrium  with  the  plasma,  their  osmotic 
pressure  must  be  equal  to  that  of  the  plasma,  and  laking  the  blood 
does  not  alter  its  freezing-point  or  its  osmotic  pressure.  The  blood 
of  the  frog  has  a  lower  osmotic  pressure,  the  normal  saline  fluid  for 
the  frog's  tissues  being  equivalent  to  0-65  per  cent,  sodium  chloride 
solution. 

THE  ELECTRICAL  CONDUCTIVITY  OF  THE  BLOOD 

In  a  solution  it  is  only  the  dissociated  ions  which  have  the  power  of 
carrying  electric  discharges.  The  conductivity  of  a  solution  of  pure 
urea  or  pure  glucose  would  not  differ  appreciably  from  that  of  dis- 
tilled water,  since  neither  of  these  substances  is  ionised  in  solution. 
The  conductivity  of  blood- serum  is  therefore  determined  almost 
entirely  by  its  content  in  salts.  Since  this  is  approximately  constant, 
the  conductivity  of  serum  varies  within  very  narrow  limits.  The  con- 
ductivity of  defibrinated  blood  varies,  however,  within  wide  limits,  since 
the  outer  limiting  layer  of  the  corpuscles  is  impermeable  to  many  of 
the  ions  of  the  salts  of  the  serum.  The  corpuscles  present  a  resistance 
to  the  passage  of  the  charged  ions  and  therefore  of  the  electric  current 
through  them,  so  that  the  larger  the  number  of  corpuscles  contained 
in  a  given  specimen  of  blood  the  lower  will  be  the  conductivity  of  the 
latter.  Stewart  has  made  use  of  this  fact  as  a  basis  for  a  method  of 
determining  the  relative  volume  of  corpuscles  and  plasma. 

The  Electrical  Conductivity  of  the  Entire  Blood  as  compared  with 

THAT   OF   ITS   vSeRITM.       (StEWART.) 

The  relative  amount  of  serum  can  be  given  by  the  formula  : 

p^^J^    (m-\{h)) 


QUANTITY  AND  COMPOSITION  OF  BLOOD 


973 


where  p  is  the  number  of  c.c.  of  serum  in  100  c.c.  of  blood  ;  X  (6),  X  («),  the 
conductivity  respectively  of  the  blood  and  serum  (both  measiu-ed  at  or  reduced 
to  5°  C.  and  expressed  in  reciprocal  Ohms  x  10^).  A  reciprocal  Ohm  is  the 
conductivity  of  a  mercury  column  1-063  metres  long  and  1  square  millimetre  in 
section. 

THE  GENERAL  COMPOSITION  OF   THE   BLOOD 

The  general  composition  of  the  blood  has  been  determined  by 
Karl  Schmidt  in  man,  and  by  Abderhalden  in  the  horse  and  bullock. 
The  results  are  given  in  the  following  Tables  : 

Blood  of  a  Man  Twenty-five  Yeabs  of  Age 

One  Thousand  Grammes  of  Blood  crmtain 

513-02  Blood-Corpuscles. 

Water         ....     349-69 
Substances  not  vaporising  at 


120° 


Haematin    . 

'  Blood-casein,'  &c. 

Inorganic  constituents 


Chlorine 
Sulphuric  acid 
Phosphoric  acid 
Potassium  . 
Sodium 

Phosphate  of  lime 
Phosphate  of  magnesium 
Oxygen 


486-98  Inter^itial  Fluid  {Plasma). 

Water  ....    439-02 

Substances  not  vaporising  at 

120°         ....      47-96 


163-33 

7-70 

151-89 

3-74 


0-898^ 

f 

0-031 

0-695 

1-586 

0-241 

0-048 

0-031 

0-206  J 

V. 

(including  0-512  iron) 
(excluding  iron) 


'Chloride  of  potassium. 
Sulphate  of  potassium 
Phosphate  of  potassium 
Phosphate  of  sodium  . 
Soda. 

Phosphate  of  lime 
Phosphate  of  magnesium 

Total 


Fibrin 

3-93 

'  Albumen,'  &c. 

39-89 

Inorganic  constituents . 

4-14 

Chloruae 

1-722'j 

^Sulphate  of  potassium 

Sulphuric  acid 

0-063 

Chloride  of  potassium . 

Phosphoric  acid  . 

0-071 

Chloride  of  sodium 

Pottkssium  . 

0-153 

Phosphate  of  sodium  . 

Sodium 

1-661 

Soda. 

Phosphate  of  lime 

0-145 

Phosphate  of  lime 

Phosphate  of  magnesium 

0-106 

Phosphate  of  magnesium 

Oxygon 

0-221 

^ 

1-887 
0-068 
1-202 
0-325 
0-175 
0-048 
0-031 

3-736 


Total 


0-137 
0-175 
2-701 
01 32 
0-746 
0145 
0-106 

4-142 


Specific  Gravity  =  1-0599. 


974 


PHYSIOLOGY 


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QUANTITY  AND  COMPOSITION  OF  BLOOD  975 

The  important  points  to  be  drawn  from  these  analyses  may  be 
summarised  as  follows.  Blood  contains  from  rather  over  one-third 
to  one-half  of  its  weight  of  corpuscles.  It  contains  from  20  per  cent, 
to  25  per  cent,  solids.  Blood- plasma  is  resolved  by  clotting  into  serum 
and  fibrin.  The  fibrin  forms  only  0-2  to  0-4  per  cent,  of  the  total 
weight  of  blood.  The  serum  contains  in  100  parts  8  to  9  parts  of 
solids,  of  which  7  to  8  parts  consist  of  proteins,  while  the  salts  make 
up  about  1  part.  The  chief  salt  present  in  the  serum  is  sodium 
chloride,  which  constitutes  60  per  cent,  of  the  ash.  Next  to  this  comes 
sodium  carbonate,  about  30  per  cent.,  and  besides  these  two  we  find 
traces  of  potassium,  sodium,  and  calcium  chlorides  and  phosphates. 
Traces  of  fats,  cholesterin,  lecithin,  dextrose,  urea,  and  other  nitro- 
genous extractives  are  constantly  found  in  the  serum.  The  fats  are 
much  increased  after  a  meal  rich  in  them  and  may  give  the  serum  a 
milky  appearance.  The  red  corpuscles  contain  from  .30  to  40  per  cent, 
total  sohds.  Of  the  solid  constituents  haemoglobin  forms  nine-tenths  ; 
the  other  tenth  corresponds  to  the  stroma  consisting  of  stroma  protein 
(nucleo-prot^in).  lecithin,  cholesterin,  and  salts.  There  is  a  striking  con- 
trast between  the  salts  of  the  corpuscles  and  those  in  the  serum,  the 
former  consisting  chiefly  of  potassium  phosphate,  the  latter  of  sodium 
chloride,  which  in  some  animals  is  entirely  wanting  in  the  corpuscles. 

THE  PROTEINS  OF  THE  PLASMA 
The  plasma  is  generally  described  as  containing  a  number  of 
different  proteins  belonging  to  the  class  of  coagulable  proteins.  No 
albumoses  or  peptones  are  present.  Since  the  plasma  in  clotting 
gives  rise  to  fibrin  and  serum  we  may  divide  its  protein  constituents 
into  those  which  are  the  precursors  of  fibrin  and  those  which  are  still 
contained  in  the  serum. 

THE  PRECURSORS  OF  FIBRIN.  Most  of  these  have  been  dealt 
with  in  discussing  the  causation  of  coagulation.  It  only  remains  for 
us  here  to  mention  some  of  the  chemical  features  of  fibrinogen  and  its 
product  fibrin.  Fibrinogen  is  best  separated  by  Hammarsten's 
method,  namely,  half- saturation  with  sodium  chloride,  or  by  the  use  of 
ammonium  sulphate.  Fibrinogen  is  precipitated  between  13  and 
28  per  cent,  saturation  with  ammonium  sulphate,  whereas  no  other 
globulins  are  precipitated  until  the  saturation  amounts  to  29  per  cent, 
of  ammonium  sulphate.  Fibrinogen  obtained  in  either  of  these  ways 
can  be  purified  by  re-solution  and  re-precipitation,  but  loses  its  solu- 
bility in  the  process,  so  that  every  time  it  is  precipitated  some  of 
the  substance  becomes  insoluble.  The  insoluble  fibrinogen  resembles 
fibrin  in  many  characters,  but  does  not  swell  in  the  presence  of  dilute 
acids  as  fibrin  does.  Fibrinogen  is  soluble  in  dilute  alkali,  from  which 
it  may  be  precipitated  by  careful  neutralisation.     Fibrinogen  in  salt 


976  PHYSIOLOGY 

solution  coagulates  at  56°  C.  A  small  amount,  however,  remains  in 
solution  and  is  not  coagulated  until  65°  C.  is  reached.  Fibrinogen  can 
be  therefore  described  as  a  globulin  occurring  in  the  plasma  and  con- 
verted on  coagulation  into  fibrin.  The  other  precursors  of  fibrin, 
namely,  those  involved  in  the  production  of  thrcttnbin  and  called 
thrombokinase  and  thrombogen,  seem  to  be  phosphorus-containing 
proteins  perhajjs  belonging  to  the  class  of  nucleo-proteins.  Their  chief 
characteristics  have  already  been  dealt  with. 

FIBRIN.  Fibrin  is  easily  obtained  by  whipping  blood  as  it  flows 
from  the  vessels  with  a  bundle  of  wires  or  twigs  and  then  washing  the 
stringy  threads  so  obtained  under  a  stream  of  water.  As  prepared  in 
this  way  it  always  contains  fragments  of  leucocytes,  blood- platelets, 
and  stromata,  which  have  become  entangled  in  its  meshes.  In  order 
to  prepare  fibrin  in  a  pure  state  it  is  necessary  to  get  it  by  the  action  of 
fibrin  ferment  on  a  pure  solution  of  fibrinogen.  Fibrin  is  a  white 
stringy  substance  insoluble  in  water  and  in  dilute  salt  solutions.  It 
slowly  dissolves  in  5  per  cent,  solutions  of  sodium  chloride,  sodium 
sulphate,  potassium  nitrate,  &c.,  but  is  converted  in  this  process  into 
c^oluble  globuhns.  It  is  probable  that  its  solution  is  effected  by  the 
agency  of  minute  traces  of  proteolytic  ferment  present  in  the  blood  and 
adherent  to  the  fibrin  as  it  is  precipitated.  This  probability  is 
strengthened  by  the  fact  that  a  certain  amount  of  albumoses  is  always 
found  in  the  fluid  along  with  the  soluble  globulins.  In  dilute  acid, 
such  as  0-2  per  cent,  hydrochloric  acid,  fibrin  swells  into  a  clear  jelly 
which  very  slowly  undergoes  solution  with  the  formation  of  acid 
albumen  and  proteoses. 

THE  PROTEINS  OF  THE  SERUM.  The  serum  proteins  are 
generally  grouped  in  two  classes,  namely,  the  serum  albumens  and  the 
serum  globulins.  All  the  proteins  are  completely  precipitated  by 
saturation  with  ammonium  sulphate.  By  half- saturation  with  this 
salt  only  the  globulins  are  precipitated  and  can  be  separated  from 
the  serum  albumens  by  filtration.  The  proportion  of  globulin  to 
albumen  as  determined  in  this  way  is  known  as  the  '  protein  quotient.' 
It  varies  in  different  animals,  but  in  the  same  individual  it  is  almost 
constant  in  the  blood,  serum,  lymph,  and  serous  transudations, 
though  the  total  amounts  of  protein  in  these  may  be  very 
different. 

SERUM  ALBUMEN.  Serum  albumen  remains  in  the  serum  after 
haff- saturation  with  ammonium  sulphate.  It  can  be  precipitated  from 
this  by  complete  saturation  with  ammonium  sulphate  or  sodio- 
magnesium  sulphate,  or  in  the  crystalHne  form  by  slight  acidification, 
as  in  Hopkin's  method  described  on  p.  80.  Serum  albumen  is 
soluble  in  distilled  water.  Its  solutions  therefore  can  be  dialysed 
indefinitely  without  any  precipitation  taking  place. 


QUANTITY  AND  COMPOSITION  OF  BLOOD  977 

THE  GLOBULINS.  The  globulins  of  serum,  known  as  para- 
globulin  or  serum  globulin,  are  obtained  by  half- saturation  with 
ammonium  sulphate.  Their  solutions  in  salt  coagulate  at  about-75°  C. 
Since  globulin  is  insoluble  in  distilled  water  it  is  precipitated  on 
dialysing  serum  against  distilled  water.  The  precipitate  obtained  in 
this  way  is  not.  however,  so  great  in  extent  as  that  obtained  on  half- 
saturation,  and  on  this  account  the  globulin  fraction  of  the  serum 
proteins  has  been  divided  into  two  fractions,  namely,  euglobulin, 
precipitable  by  dialysis,  and  pseudo-globulin.  n(jt  precipitable  by 
dialysis,  but  thrown  down  on  ha  If -saturation  with  ammonium  sulphate. 

A  thorough  study  of  serum  globulin  by  Hardy  has  shown  that 
this  body  forms  adsorption  combinations  with  acids,  alkaUes,  or 
neutral  salts.  With  acids  and  alkalies  the  giobuhn  forms  '  salts  '  which 
ionise  in  solution  so  that  in  an  electric  field  the  entire  mass  of  protein 
moves.  These  salts  cannot  be  precipitated  by  dialysis.  In  them  the 
giobuhn  acts  much  more  strongly  as  an  acid  than  as  a  base,  so  that  a 
weak  acid,  such  as  acetic  acid,  has  a  much  smaller  dissolving  power 
over  globulin  than  has  the  equivalent  amount  of  hydrochloric  acid, 
and  boracic  acid  has  a  very  shght  power  indeed.  The  weak  basic 
character  of  globulin  causes  its  salts  in  weak  acids  to  undergo  hydro- 
lysis with  separation  of  globulin,  so  that  in  order  to  reach  the  same 
grade  of  solution  with  a  weak  acid  as  with  a  strong  acid  a  great  excess  of 
the  acid  is  necessary.  Owing  to  the  much  stronger  acid  character  of 
globulin  it  is  found  that  weak  ammonia  dissolves  it  almost  as  well  as 
strong  alkalies.  With  neutral  salts  globulins  form  molecular  compounds 
which  are  soluble,  but  are  readily  decomposed  by  water  with  liberation 
of  the  insoluble  globulin.  They  are  therefore  only  stable  in  the  presence 
of  a  comparatively  large  excess  of  salt.  The  globulins  differ  from  the 
albumens  of  the  serum  in  containing  constantly  organic  phosphorus 
as  an  integral  part  of  their  molecule.  In  all  its  solutions  globulin  is 
present  in  large  molecular  aggregates,  so  that  it  is  impossible  to  filter 
a  globulin  solution  through  a  porous  clay  cell. 

THE  CONDITION  OF  THE  PROTEINS  IN  THE  BLOOD-SERUM, 
Although  it  is  easy  by  such  simple  means  as  the  addition  or  removal 
of  neutral  salts  to  separate  one  or  more  different  forms  of  protein 
from  serum,  we  have  strong  evidence  that  these  proteins  do  not  exist 
side  by  side  in  the  serum,  but  are  combined  to  form  what  we  may 
term  serum  protein,  which  acts  as  a  whole  and  differs  in  its  qualities 
from  many  of  those  of  its  constituent  globuUus  or  albumens.  When 
a  current  is  passed  through  blood-serum  no  movement  of  protein 
takes  place  (Hardy).  Alkali  globulin  therefore  cannot  be  present.  Salt 
globulin  might  be  assumed  to  be  present  since  it  does  not  ionise  in 
solution,  but  serum  is  not  precipitated  by  simple  addition  of  acid, 

62 


978  PHYSIOLOGY 

which  would  readily  precipitate  salt  globulin  in  alkaline  solution. 
Moreover  serum  can  be  readily  filtered  through  a  porous  cell,  and 
this  method  is  adopted  for  obtaining  it  free  from  contamination  by 
micro-organisms.  Globulin  in  any  of  its  solutions  will  not  pass 
through  a  porous  cell.  If  globulin  be  present  as  such  in  the  serum  it  is 
therefore  not  ionised,  but  the  agent  which  dissolves  it  must  be  some- 
thing more  than  alkali  or  salt,  since  either  alone  or  together  they  will 
not  produce  a  solution  which  will  pass  through  a  porous  cell.  Serum  has 
still  the  power  of  taking  up  globulin  and  will  dissolve  almost  its  own 
volume  of  precipitated  globulin,  though  in  oxalate  serum  there  is  not  a 
trace  of  alkali  globulin  nor  of  any  ionised  protein.  We  are  justified 
therefore  in  concluding  that  serum  protein  may  be  regarded  as  a 
complex  unit.  By  simple  means,  such  as  dialysis,  dilution,  or  addition 
of  salt,  this  unit  can  be  broken  up  with  the  separation  of  the  various 
proteins  which  we  have  designated  as  serum  albumen  and  serum 
globulin,  &c.  The  question  naturally  suggests  itself  whether  in 
plasma  we  have  not  a  similar  combination  of  all  its  varied  colloidal 
constituents  to  form  one  labile  mass  of  fluid  protoplasm. 


CHAPTER  XIII 
THE  PHYSIOLOGY  OF  THE  CIRCULATION 

SECTION  I 

GENERAL  FEATURES  OF  THE  CIRCULATION 

In  order  that  the  nutrition  of  the  tissues  may  be  properly  carried  out, 
and  that  they  may  receive  a  continual  supply  of  nourishment  from 
the  alimentary  canal,  and  of  oxygen  from  the  lungs,  and  be  able  to  free 
themselves  of  their  waste  products,  the  blood  which  flows  through 
them  must  be  continually  renewed.  For  this  purpose  every  part  of 
the  body  is  supplied  with  tubes — blood-vessels — of  various  sizes  and 
structure. 

In  the  tissues  the  blood  is  passing  continuously  through  a  thick 
meshwork  of  capillaries,  hair-like  vessels  with  walls  consisting  of  a 
single  layer  of  delicate  endothelial  cells  which  permit  of  a  free  inter- 
change of  material  by  diffusion  between  the  blood  within  and  the 
tissue  fluid  outside  the  vessel.  The  movement  of  the  blood  is  main- 
tained by  a  hollow  muscular  organ,  the  heart,  placed  in  the  chest,  the 
blood  being  brought  from  the  heart  to  the  tissues  by  thick-walled 
tubes,  the  arteries,  and  being  carried  back  from  the  tissues  to  the 
heart  by  a  system  of  thin-walled  vessels,  the  veins. 

In  all  the  vertebrates  the  vascular  system  is  closed,  i.e.  communi- 
cates at  no  point  with  the  tissue  spaces  or  coelomic  cavity.  It  is  found 
in  its  simplest  form  in  fishes  (Fig.  367,  \),  where  the  heart  consists  of  one 
auricle  and  one  ventricle.  The  blood  is  received  from  the  great  veins 
into  the  auricle.  The  walls  both  of  auricle  and  ventricle  contract 
rhythmically.  By  the  contraction  of  the  auricle  the  blood  is  forced 
into  the  ventricle,  and  this,  when  it  contracts,  sends  the  blood  on 
into  the  bulbus  arteriosus.  From  the  bulbus  the  blood  passes  through 
the  branchial  arteries  into  the  gills,  where  it  takes  up  oxygen  from  the 
surrounding  water,  and  then  flows  on  into  the  aorta,  by  which  it  is 
distributed  to  the  various  organs  of  the  body.  From  the  capillaries 
of  these  organs  the  blood  is  collected  by  the  veins  and  is  carried  once 
more  back  to  the  auricle.  The  fish  heart  is  thus  entirely  on  the 
venous  side  of  the  vascular  system. 

In  amphibia,  such  as  the  frog,  the  heart  consists  of  two  auricles  and 

979 


980 


PHYSIOLOGY 


one  ventricle.  The  right  auricle  receives  venous  blood  from  the 
body  by  means  of  the  vense  cavse  and  forces  it  by  its  contraction  into 
the  ventricle.  From  the  ventricle  the  blood  passes  into  the  aorta, 
whence  it  is  carried  partly  by  the  pulmonary  artery  to  the  lungs,  partly 
by  arteries  to  the  different  organs  of  the  body.  The  blood  which  has 
passed  through  the  lungs  and  been  arterialised  flows  through  the 
pulmonary  veins  to  the  left  auricle,  whence  it  passes  into  the  ventricle 
and  mixes  with  the  venous  blood  which  is  arriving  from  the  right 
auricle.  The  pulmonary  circulation  is  thus  merely  a  branch  of  the 
general  or  systemic  circulation.     The  bulbus   aortse    in    the  frog  is 

A  B  C 


Fig.  3G7.     Diagram  of  circulatory  system  in  A,  fiish  ;    B,  amphibian  (frog) ; 

C,  mammal. 
V,  ventricle ;     a,   ax:ricle  ;     K,   gill   capillaries ;     A,   aorta ;    c,    systemic 
capillaries;   L,  lung  capillaries;   r,  I,  right  and  left  auricles;  rV,  IV,  right 
and  left  ventricles. 

divided  into  two  parts  by  means  of  a  spiral  valve,  by  which  a  partial 
separation  of  the  blood  coming  from  the  right  and  left  auricles  is 
effected,  and  the  venous  blood  from  the  right  auricle  directed  especially 
into  the  pulmonary  artery. 

In  birds  and  mammals  the  heart  has  become  entirely  divided  into 
two  halves,  right  and  left,  which  have  no  communication  with  one 
another  except  by  way  of  the  blood-vessels  and  capillaries.  The 
right  heart  receives  the  venous  blood  from  all  parts  of  the  body  and 
sends  it  on  to  the  right  ventricle,  whence  it  is  forced  into  the  lungs 
along  the  pulmonary  artery.     In  the  lungs  it  takes  up  oxygen  and 


GENERAL  FEATURES  OF  THE  CIRCULATION         981 

becomes  arterial  and  is  returned  by  the  pulmonary  veins  to  the  left 
auricle  and  so  to  the  left  ventricle.  The  rhythmic  contractions  of  the 
left  ventricle  then  force  the  blood  into  the  aorta,  whence  by  the 
branching  arteries  it  is  carried  to  all  parts  of  the  body.  The  whole 
vascular  system  is  distensible  and  elastic,  so  that  its  capacity  will 
increase  with  the  pressure  of  the  blood  contained  in  it.  Since  the 
driving  force  is  furnished  by  the  heart  the  pressure  which  causes  the 
flow  of  blood  through  the  system  must  decline  as  we  pass  from  the 
arterial  to  the  venous  side.  The  chief  function  of  the  large  arteries  is  to 
serve  as  elastic  conduits,  whereas  the  small  arteries  or  arterioles  leading 
from  the  arteries  to  the  capillaries  have  in  addition  the  function  of 
regulating  the  amount  of  blood  flowing  through  the  capillary  area 
of  the  organs  which  they  supply.  The  veins  have  the  function  of 
conducting  blood  at  a  low  pressure  from  capillaries  to  heart  and  of 
storing  up  any  excess  of  blood  which  is  not  immediately  taken  up  by 


Id- 


Fig.  368.     Tran.^vtroi;  section  of  part  of  the  wall  of  the  posterior 

tibial  artery  {  x  7-5). 

o,  endothelial  and  sub-endothelial  layers  of  intima  ;  h,  lamina  of  elastic  tissue ; 

c,  media  consisting  of  muscle  fibres  ;   d,  adventitia.     (Schafer.) 

the  heart.  Corresponding  to  this  difference  in  function  we  find 
variations  in  the  structure  of  the  blood-vessels  according  to  their 
situation  in  the  circuit. 

The  vessels  which  carry  the  blood  from  the  heart  to  the  tissues, 
the  arteries,  are  thick -walled,  and  contain  an  abundance  of  muscular 
and  elastic  elements  in  their  walls.  The  typical  medium-sized  artery 
is  described  as  consisting  of  three  coats  (Fig.  368)  :  an  iiitima  lined 
by  a  continuous  layer  of  flattened  endothelial  cells,  which  rest  on  a 
well-marked  lamina  of  yellow  elastic  tissue  ;  a  media  composed  of 
unstriated  muscular  fibres  arranged  longitudinally  and  circularly ; 
and  an  external  coat  or  adventitia  of  fibrous  tissue,  with  a  number  of 
longitudinal  elastic  fibres.  Near  the  heart,  in  the  great  vessels  such 
as  the  aorta  and  its  larger  branches,  there  is  a  preponderance  of 
elastic  tissue  as  compared  to  the  muscular  ;  and  we  find  in  the  media 
alternate  layers  of  muscle  fibres  and  fenestrated  elastic  membranes. 
In  the  smallest  arteries,  on  the  other  hand,  the  arterioles,  the  elastic 
element  entirely  disappears,  so  that  the  wall  consists  of  muscle  fibres, 


982 


PHYSIOLOGY 


chiefly  circular,  lined  by  the  endothelium.  In  the  latter  vessels  a 
contraction  of  their  walls  may  result  in  an  entire  obliteration  of 
the  lumen,  so  shutting  off  altogether  the  supply  of  blood  to  the 
capillaries  beyond.  In  the  veins  the  same  three  coats  can  be  dis- 
tinguished as  in  the  typical  artery,  but  the  wall  of  the  vessel  is  much 
thinner  in  proportion  to  the  lumen.  In  the  vein  moreover  there  is  a 
preponderance  of  the  fibrous  tissue  elements,  the  muscular  and 
elastic  tissue  being  but  little  marked.  On  this  account  the  vein 
collapses  unless  it  is  distended  by  some  internal  pressure.  The 
histological  difference  between  veins  and  arteries  is  of  considerable 
importance  for  the  understanding  of  the  distribution  of  pressures 
in  the  vascular  system,  since  the  distensibility  and  reaction  to  pressure 

Capacity  in  c.c. 


120        130       140 


mm.  Hg 


Fig.  369.  Curves  of  distensibility  of  an  artery  (thick  line)  and  of  a  vein  (thin  line). 
The  figures  at  the  left  side  of  the  diagram  represent  the  capacity  of  a  section  f  f 
the  vessel  when  distended  under  a  certain  pressure,  expressed  by  the  figures 
on  the  base  line  in  mm.  Hg.     (Constructed  from  figures  given  by  Roy.) 


of  these  vessels  are  conditioned  by  their  structure.  In  Fig.  369  is 
represented  the  extensibility,  i.e.  the  increase  in  capacity  of  an  artery 
and  a  vein  under  gradually  increasing  internal  pressure.  It  will  be 
seen  that  an  artery  which  has  a  certain  capacity  at  zero  pressure 
gradually  distends  with  increasing  pressure.  The  increase  in  capacity 
is  small  at  first,  and  becomes  most  rapid  between  90  and  110  mm.  Hg. 
After  this  point  every  increment  of  pressure  brings  about  a  gradually 
diminishing  increment  of  capacity.  Thus  a  change  of  internal  pressure 
causes  the  greatest  change  in  capacity  when  the  pressure  in  the  artery 
corresponds,  as  we  shall  see,  to  the  average  arterial  pressure  in  the 
normal  animal.  In  the  vein,  on  the  other  hand,  the  capacity,  which  is 
nothing  at  zero  pressure,  becomes  considerable  on  raising  the  pressure 
to  1  mm.  Hg.     A  further  rise  of  pressure  to   10  mm.  Hg  causes  a 


GENERAL  FEATURES  OF  THE  CIRCULATION        983 

considerable  increase  in  volume,  but  from  this  point  the  increments 
of  volume  with  risinjj  pressure  rapidly  diminish.  Whereas  the  artery  is 
most  distensible  at  about  100  mm.  Hg,  the  vein  has  its  limits  of 
optimum  distensibility  between  0  and  10  mm.  Hg. 

As  the  arteries  branch,  although  each  branch  is  smaller  than  the 
parent  vessel,  the  total  area  of  the  two  branches  into  which  the  vessel 
divides  is  greater.  Thus  there  is  a  continual  increase  in  the  cross 
area  of  the  bed  of  the  blood-stream  as  we  pass  from  the  heart 
towards  the  periphery.  This  increase  is  especially  marked  at  the 
junction  between  the  capillaries  and  the  arterioles  at  one  side  and  the 
venules  on  the  other,  so  that  the  total  area  of  the  bed  in  the  region 
of  the  capillaries  can  be  taken  as  about  800  times  that  of  the  area  of 
the  aorta  where  the  blood  leaves  the  heart. 

On  cutting  through  an  artery,  blood  escapes  from  the  central  end, 
i.e.  that  nearest  the  heart,  with  great  force  and  in  a  series  of  jerks, 
each  of  which  corresponds  to  a  contraction  of  the  ventricles.  This 
manner  of  escape  shows  that  in  the  arteries  the  blood  is  at  a  high 
pressure,  and  that  the  flow  from  the  heart  to  the  periphery  is  a  pul- 
satory one.  The  same  lesson  may  be  learnt  by  connecting  a  long 
tube  with  the  central  end  of  a  divided  artery.  This  experiment, 
which  was  first  performed  by  the  Rev.  Stephen  Hales,  may  be  described 
in  his  own  words  : 

"  In  December  I  caused  a  mare  to  be  tied  down  alive  on  her  back  ;  she  was 
fourteen  hands  high,  and  about  fourteen  years  of  age,  had  a  Fistula  on  her 
Withers,  was  neither  very  lean,  nor  yet  lusty  :  Having  laid  open  the  left  criural 
Artery  about  three  inches  from  her  belly,  I  inserted  into  it  a  brass  Pipe,  whose 
bore  was  one  sixth  of  an  inch  in  diameter  ;  and  to  that,  bj'  means  of  another 
brass  Pipe  which  was  fitly  adapted  to  it,  I  fixed  a  glass  Tube,  of  nearly  the  same 
diameter,  which  was  nine  feet  in  length  :  Then  untying  the  Ligature  on  the 
Artery,  the  blood  rose  in  the  Tube  eight  feet  three  inches  perpendicvdar  above 
the  level  of  the  left  Ventricle  of  the  heart :  But  it  did  not  attain  to  its  full  height 
at  once  ;  it  rushed  up  about  half  way  in  an  instant,  and  afterwards  gradually 
at  each  Pulse  twelve,  eight,  six,  four,  two,  and  sometimes  one  inch  :  When  it 
was  at  its  full  height,  it  would  rise  and  fall  at  and  after  each  Pulse  two,  three, 
or  four  inches  ;  and  sometimes  it  would  fall  twelve  or  fomteen  inches,  and  have 
there  for  a  time  the  same  Vibrations  up  and  down  at  and  after  each  Pulse,  as  it 
had,  when  it  was  at  its  full  height ;  to  which  it  would  rise  again,  after  forty  or 
fifty  Pulses." 

The  method  adopted  by  Hales  of  measuring  the  lateral  pressure  of 
blood  in  the  vessels  offers  very  considerable  drawbacks.  The  manipu- 
lation of  such  long  tubes  is  awkward,  and  the  blood  which  escapes  into 
the  tubes  very  soon  clots  and  renders  further  observation  impossible. 
It  is  therefore  customary  when  we  desire  to  gain  an  idea  of  the  average 
pressure  in  any  blood-vessel,  especially  in  an  artery,  to  use  a  mercurial 
manometer  for  this  purpose.  This  instrument,  which  was  first 
applied  to  physiological  purposes  by  Ludwig,  consists  of  a  U  -tube  with 


984 


PHYSIOLOGY 


two  vertical  limbs  about  eighteen  inches  in  height,  which  is  half-filled 
with  clean  mercury.  On  the  surface  of  the  mercury  of  one  limb  is 
a  float  of  vulcanite  from  which  a  stifi  fine  rod  of  straw,  glass,  or  steel 
rises,  bearing  on  its  upper  end  the  writing- point.  This  point  may  be 
adjusted  so  as  to  write  on  the  blackened  glazed  surface  of  a  moving  sheet 
of  paper  (Fig.  370).  (The  arrangement  for  imparting  a  continuous  move- 
ment to  a  sheet  of  glazed  paper  is  known  as  a  kymograph.)  Instead 
of  smoking  the  paper  a  pen  may  be  fitted  to  the  end  of  a  rod  and 
its  excursions  recorded  in  ink  on  a  moving  band  of  white  paper. 
The  other  limb  of  the  manometer  is  connected  by  a  flexible  inex- 
tensible  tube  with  a  small  tube  or  cannula  which  is  tied  into  the 


Fig.  370.     Airangciiicnt  of  a})paratu.s  for  taking  hloodjire.s.sure  tracing. 

a,  artery  (carotid) ;   c,  cannula  ;    d,  tliree-way  cock  ;    m,  mercurial  manometer  ; 

b,  drum  covered  with  smoked  paj^er  ;  x,  tube  to  pressure  bottle. 


central  end  of  an  artery,  a  clip  being  previously  placed  on  the  artery 
so  as  to  prevent  the  escape  of  blood  during  the  insertion  of  the  cannula. 
To  the  manometer  is  connected  a  three-way  tap  by  means  of  which 
the  manometer  can  be  placed  in  communic^ation  with  the  artery  alone, 
or  with  the  artery  and  a  pressure  bottle.  By  means  of  the  latter  the 
whole  system  is  filled  with  magnesium  sulphate  solution  (25  per  cent.) 
or  a  half- saturated  solution  of  sodium  sulphate,  at  a  pressure  of 
150  mm.  Hg.  The  pressure  bottle  is  then  cut  off  so  that  the  manometer 
remains  in  connection  only  with  the  cannula,  the  mercury  in  one  limb 
being  150  millimetres  above  that  in  the  other.  The  clip  is  then  taken 
off  the  artery.  The  pressure  in  the  cannula  being  greater  than  that  in 
the  artery,  a  small  amount  of^^the  fluid  used  to  fill  the  tubes  runs  into 


GENERAL  FEATURES  OF  THE  CIRCULATION 


985 


the  circulation.  The  mercury  in  the  manometer  drops  to  a  height  of 
100  to  120  mm.  Hg  and  stays  about  that  level,  rising  and  falling  slightly 
with  each  heart-beat  (Fig.  372).  The  blood  which  enters  the  cannula 
at  each  heart-beat  does  not  clot  for  a  considerable  time  owing  to  its 
admixture  with  the  saline  fluid  used  for  filling  the  cannula  and 
connecting  tubes. 

If  a  vein  be  ligatured,  it  swells  up  on  the  distal  side  of  the  ligature. 
If  the  vein  be  cut  across,  blood  escapes  chiefly  from  the  peri- 
pheral end,  and  instead  of  spurting  out  to  a  considerable  distance 
with  each  heart- beat  it  flows  steadily,  but  with  very  little  force,  so  that 
light  pressure  by  a  bandage  is  sufficient  to  restrain  the  haemorrhage. 
If  a  mercurial  manometer  be  connected  with  the  vein  the  pressure 
in  its  interior  is  found  to  amount  to  only  a  few  mm.  Hg. 


FiQ.  371.     Scheme  of  bloud  pressure  in — -A,  the  arteries  ;  c,  capillaries  ; 

and  V,  veins. 

oo,  line  of  no  pressure  ;  lv,  left  ventricle  ;   RA,  right  auricle  ;    BP,  height 

of  blood  pressure. 


By  taking  the  pressure  at  different  parts  of  the  circulation  we 
obtain  a  distribution  which  is  represented  roughly  in  the  accompanying 
diagram  (Fig.  371 ).  The  blood  pressure,  which  is  about  100  to  120  mm. 
Hg  in  the  large  arteries  near  the  heart,  falls  only  slowly  in  these 
arteries,  so  that  in  the  radial  artery  it  is  not  very  much  below  that 
in  the  aorta.  Between  the  medium- sized  arteries  and  capillaries 
there  is  a  very  extensive  fall  of  pressure  as  the  blood  passes 
through  the  arterioles,  so  that  in  the  capillaries  the  pressure  on  an 
average  may  be  taken  as  20  to  40  mm.  Hg  ;  from  the  capillaries 
to  veins  the  blood  pressure  falls  steadily  until  in  the  big  veins  near 
the  heart  it  may  be  negative. 


SECTION  II 


THE  BLOOD   PRESSURE  AT  DIFFERENT  PARTS 
OF  THE  VASCULAR  CIRCUIT 

THE  ARTERIAL  BLOOD  PRESSURE.  The  arterial  blood  pressure 
as  recorded  by  a  mercurial  manometer  exhibits  a  series  of  pulsa- 
tions corresponding  to  each  heart-beat  (Fig.  372).  These  pulsations 
are  due  to  the  fact  that  the  artery  becomes  fuller  each  time  the 
ventricle  forces  more  blood  into  it  during 
its  systole.  Between  the  beats  of  the  heart, 
i.e.  during  diastole,  the  aortid  valves  are 
closed,  and  blood  escapes  from  the  arteries 
into  the  capillaries  and  veins,  so  that  the 
blood  pressure  falls.  The  mercurial  mano- 
meter does  not  register  these  rapid  changes 
[a  of  pressure  in  the  artery  with  any  accuracy. 
The  inertia  of  the  mercury  is  such  that  it 
I  takes  some  time  to  be  set  into  movement  by 
the  rise  of  pressure  in  the  artery,  and 
before  it  has  attained  its  full  height  the 
pressure  in  the  artery  has  already  begun  to 
fall.  With  a  very  wide -tubed  manometer 
the  oscillations  may  be  almost  imperceptible 
owing  to  the  mass  of  mercury  that  has  to  be  moved  at  each 
heart- beat.  Such  a  manometer  gives  a  true  record  of  what  is 
known  as  the  '  mean  arterial  pressure.'  In  order  to  determine  the 
true  course  of  the  pressure  in  the  heart  it  is  necessary  to  diminish 
to  the  utmost  possible  extent  the  inertia  of  the  moving  parts  of  the 
recording  instrument,  and  to  employ  some  manometer  such  as  that 
of  Hiirthle  or  of  Frank,  in  which  the  pressure  is  measured  by  recording 
the  stretching  of  an  elastic  membrane.  Such  instruments  will  be 
described  later  in  dealing  with  the  changes  of  pressure  in  the  ventricle 
during  contraction. 

In  the  living  animal  the  variation  in  the  arterial  pressure  at  each 
heart-beat  is  much  greater  than  would  be  anticipated  from  an 
inspection  of  the  tracing  given  by  the  mercurial  manometer.  The 
highest  pressure  which  occurs  wliiie  blood  is  passing  from  the  heart 
into  the  aorta  is  called  the  systolic  arterial  pressure;    the  pressure 

986 


Fig.  372.      Blood-pressure 
tracing  taken  with  mer- 
curial manometer  (from 
carotid  of  rabbit). 
A,  abscissa   or  line  of 
no  pressure. 


THE  BLOOD  PRESSURE 


987^ 


at  the  end  of  diastole,  just  before  the  heart  begins  to  force  a  fresh 
quantity  of  blood  into  the  aorta,  is  the  diastolic  pressure ;  and  the 
range  between  these  two  extremes  is  known  as  the  pulse  pressure. 
Thus  in  the  dog,  with  a  mean  pressure  of  about  120  mm.  Hg  in  tlie 
aorta,  the  systolic  pressure  may  be  as  much  as  160,  while  the 
diastolic  pressure  is  only  100  mm.  In  this  case  the  pulse  pressure 
would  be  60  mm.  Hg.  In  man  the  systolic  pressure,  as  measured 
in  the  brachial  artery,  is  under  normal  conditions  about  110  mm., 
while  the  diastolic  pressure  is  only  65  to  75  mm.,  so  that  the  pulse 
pressure  is  about  45  mm.  Hg.  As  we  pass  outwards  towards  the 
periphery  the  pulse  pressure  becomes  less  and  less  marked,  until 
finally  in  the  capillaries  and  veins  there  is  no  pulse-wave  perceptible. 

THE   DETERMINATION  OF  THE  BLOOD  PRESSURE  IN   MAN 
It  is  important  fur  clinical  purposes  to  be  able  to  determine  even  approxi- 
mately the  blood -pressure  in  the  different  parts  of  the  vascular  sjstem  in  man, 

and  various  methods  have  been 
devised  for  this  purpose.  The  de- 
termination of  the  systoUc  blood 
pressure  in  the  arteries  is  easily 
carried  out  by  the  use  of  Riva 
Rooci's  sphygmomanometer.  Tliis 
apparatus  (Fig.  373)  consists  of  a 
leather  or  canvas  band  about  10 
cm.  wide,  wliich  can  be  buckled 
closely  round  the  upper  arm.  In- 
side this  band  is  a  rubber  bag  of 
the  same  shape,  which  commu- 
nicates by  a  rubber  tube  with  a 
mercurial  manometer  and  by  a 
tliree-way  tap  with  a  pressure 
bulb  or  bicycle  pump,  or  mth  the  external  air.  The  band  is  buckled  round 
the  arm  and  the  fingers  of  the  observer  are  placed  on  the  radiM  pulse. 
The  bag  is  then  distended  -nntli  air  so  that  it  exercises  a  pressure  on  the  arm, 
the  pressure  being  indicated  on  the  mercurial  manometer.  Air  is  forced  in 
until  the  radial  pulse  disappears.  By  means  of 
the  three-way  tap  the  air  is  then  slowly  let  out 
of  the  bag  until  the  radial  pulse  is  just  per- 
ceptible. The  height  of  the  mercurial  mano- 
meter at  this  moment  is  equal  to  the  systolic 
pressure  in  the  main  arterial  trunk  from  wliicli 
the  brachial  artery  takes  origin,  'i'he  priiici])le 
of  this  metlK)d  will  be  made  clear  by  reference  to 
the  diagram  (Fig.  374).  If  we  imagine  a  as  a  seg- 
ment of  the  brachial  artery  ])assing  tlnough  the 

tissues  which  are  surn  >uncled  by  t  lie  rubber  l)ag,  we  see  that  so  long  as  tlic  pre-ssure  in 
the  interior  of  the  artery  is  greater  tlian  that  on  the  exterior  exerted  by  the  tissues, 
the  artery'  will  be  jmtent  and  the  pulse  can  ]iass  through.  If,  however,  the  pressure 
in  the  tissues  becomes  greater  than  the  maximum  pres.sure  inside  the  artery  at 
any  time  of  the  heart-beat,  the  segment  of  artery  will  collapse  (as  in  b),  thuB 
stopping  the  transmi.ssion  of  blood  and  of  the  pulse-wave.     If  we  exclude  the 


Fig.  373.     Riva  Rocci's  sphygmomanometer. 
(C.  J.  Martin's  pattern.     Hawksley.) 


B 

Vio.  1574. 


<Sll 


OSS- 


PHYSIOLOGY 


elasticity  of  the  tissues  themselves  we  may  take  the  pressure  in  the  bag  as  repre- 
senting the  pressure  in  the  tissue  fluids  surrounding  the  artery,  so  that  the  pulse - 
obliterating  pressure  in  the  bag  will  correspond  to  the  maximum  or  systolic 
pressure  in  the  artery.  By  a  shght  modification  of  the  apparatus  it  is  possible 
to  determine  also  the  diastoUc  pressure.  For  this  purpose  the  rubber  bag  is 
connected  also  with  a  manometer  of  small  inertia,  giving  a  true  representation 


Fi(!.  :}75. 


Erlanger's  apparatus  for  recording  systolic  and  diastolic 
blood  pressures. 


of  the  actual  changes  of  pressure.  It  is  evident  that  when  the  pressure  in  the  bag 
and  in  the  tissues  surrounding  the  artery  exactly  corresponds  to  the  diastolic 
pressure,  the  artery  will  be  completely  collapsed  when  the  pressure  arrives  at 
its  lowest  point  and  unll  then  dilate  almost  to  the  utmost  with  the  systolic  rise 
of  pressure.  If  we  are  taking  a  record  of  the  pressure  changes  in  the  bag  in  this 
way,  the  pulse-waves  as  recorded  by  the  manometer  will  slowly  increase  in  size 
as  the  pressure  in  the  bag  is  gradually  raised.  At  one  point  the  waves  rapidly 
increase  and  reach  a  maximum,  marking  the  pressure  at  which  the  artery  is  just 
completely  collapsed  at  the  lowest  point  of  each  pulse-wave  (the  diastolic  pres- 
sure). As  the  pressure  is  still  further  raised  the  excursions  of  the  manometer 
tend  to  diminish  in  size,  first  slowly  and  then  rapidly,  and  the  point  of  rapid 
diminution  corresponds  to  the  systolic  pressure.  Above  this  point  the  manometer 


THE  BLOOD  PRESSURE 


989 


still  shows  small  oscillations,  due  to  the  impact  of  the  unoccluded  stump  of  the 
artery  on  the  upper  border  of  the  india-rubber  bag. 

Many  different  methods  have  been  introduced  for  the  purpose  of  recording 
the  pressure  oscillations  in  the  bag.  In  Erlanger's  apparatus  the  rubber  bag 
is  put  into  connection  with  a  thick-walled 
rubber  ball  PS  contained  in  a  glass  chamber. 
The  chamber  (Fig.  375)  communicates  with  a 
sensitive  tambour  and  also  by  means  of  "a 
capillary  opening  provided  with  a  stop-cock 
with  the  external  air.  By  this  means  the 
slow  expansion  of  the  bag  E  is  not  recorded 
by  the  tambour,  which  only  moves  with  the 
sudden  oscillations  of  pressure  due  to  each 
heart-beat.  With  this  instrument  it.  is  easy 
to  read  on  the  accompanying  mercurial 
manometer  the  poirt  at  which  the  oscil- 
lations of  pressure  in  the  bag  suddenly 
become  maximal,  and  so  to  determine  ap- 
proximately the  diastohc  pressure  in  the 
artery. 

VENOUS  PRESSURE.  To  determine  tlie  venous  pressure  in  man  we  may 
use  some  modification  of  von  Recklinghausen's  method.  A  circular,  disc-shaped, 
incomplete  rubber  bag  (Fig.  376)  is  made  by  cementing  togetlier  at  the  circum- 
ference two  rubber  discs,  each  of  which  has  a  hole  in  the  centre.  This  is  placed 
over  a  peripheral  vein  and  a  glass  plate  laid  on  the  top  (Fig.  377).  A  tube 
leads  from  the  interior  of  the  amnilar  rubber  bag  to  a  water  manometer  and  to  a 
bicycle  pump  or  bellows  for  the  injection  of  air.    On  blowing  air  into  the  bag 


L.J 


Fig.  376. 


Fig.  377. 


the  pressure  in  its  interior  rapidly  increases.  If  the  skin  and  glass  plate  have 
been  previously  smeared  witli  glycerine,  the  air  does  not  escape,  but  distends 
the  bag,  pressing  it  against  the  skin  on  tlie  one  hand  and  the  glass  plate  on  the 
other.  Through  the  hole  in  the  rubber  bag  it  is  easy  to  see  the  pressure  at  which 
the  vein  collapses — that  is  to  say,  the  point  at  wliich  the  pressure  in  the  bag  is 
equal  to  the  pressure  Avithin  the  vein.  By  a  .similar  method,  using  a  smaller  bag, 
we  may  determine  the  pressure  Mhich  is  just  sufficient  to  obhterate  tlie  capillaries 
in  any  given  area  of  the  skin,  .so  causing  a  blanching  of  the  skin  lyijig  under 
the  bag. 

The  following  Table  may  serve  to  give  an  idea  of  the  average 
height  of  the  mean  blood  pressure  at  different  parts  of  the  vascular 
system  in  man,  in  the  horizontal  position.  The  pressures  are  all 
subject    to   considerable   variations    according    to    the   activity    of 


990  PHYSIOLOGY 

the  individual  and  the  physiological  activity  of  the  various  parts  and 

organs  of  the  body : 


Large  arteries  {e.g.  carotid) 

Medium  arteries  [e.g.  radial) 

Capillaries 

Small  veins  of  arm 

Portal  vein     . 

Inferior  vena  cava 

Large  veins  of  neck 


.     90  mm.  mercury  (65-110). 
.     85  mm.        ,, 
.about     15  to  40  mm.  merciu-y. 
9  mm.  mercury. 
10  mm.         ,, 
.3  mm.         ,, 
.  from     0  to  -8  mm.  mercury 


The  cause  of  these  peculiarities  in  the  circulation  in  different  parts 
of  the  vascular  system  will  be  rendered  clearer  by  a  study  of  a  flow  of 


fluid  through  a  tube  of  uniform  bore  (Fig.  378).  If  the  tube  ag  te 
connected  with  the  reservoir  R,  fluid  will  flow  from  a  to  G  under  the 
influence  of  the  pressure  difierence  between  the  fluid  in  the  reservoir 
and  that  at  D.  The  pressure  on  the  fluid  at  each  part  of  the  tube  can 
be  measured  by  attaching  at  a  series  of  points — e.g.  at  b,  c,  d,  e,  f — 
vertical  tubes  in  which  the  fluid  will  rise  to  a  height  corresponding  to 
the  lateral  pressure  existing  at  these  several  points.  When  fluid  is 
flowing  from  A  to  g  it  will  be  found  that  the  heights  of  the  fluid  in  the 
tubes  show  a  continuous  descent,  so  that  the  line  joining  the  tops  of  the 
fluid  in  the  various  tubes  is  a  straight  one.  The  movement  of  the 
fluid  from  B  to  c  can  be  regarded  as  due  to  the  difference  of  the  pressure 
between  b  and  c.,  i.e.  P2-P3.  It  will  be  noticed  in  the  diagram  that 
the  straight  line  joining  the  tops  of  the  fluid  does  not  strike  the  surface 
of  the  fluid  in  R,  but  falls  a  little  below  it.  Of  the  total  pressure  in  R,  H, 
the  large  portion  h'  is  employed  in  overcoming  the  resistance  of  the 
tube  AG,  while  a  small  portion  h  represents  the  force  necessary  to  give 
to  the  fluid  as  it  leaves  the  reservoir  at  a  a  certain  velocity.  If  the 
flow  of  fluid  be  diminished  by  partially  clamping  the  end  at  G  the  rate  of 
tall  of  the  pressures  will  be  diminished.    The  same  efEect  will  be 


THE  BLOOD  PRESSITIE  991 

produced  either  by  raising  the  level  of  g  or  by  lowering  the  level  of 
the  reservoir  and  so  the  pressure  at  a. 

The  difference  of  pressure  between  any  two  points,  i.e.  between 
D  and  E.  mav  be  regarded  as  that  pressure  which  is  necessary  to  main- 
tain a  certain  velocity  of  the  fluid  against  the  resistance  offered  by  the 
friction  of  the  fluid  in  contact  with  the  walls  of  the  tube.  This  friction, 
and  therefore  tlie  resistance  to  the  flow,  can  be  altered  by  diminishing 
the  diameter  of  the  tube,  when  a  larger  difference  of  pressure  will  be 
necessarv  in  order  to  maintain  the  same  velocity  of  flow.  This  can  be 
shown  bv  introducinfr  a  resistance  between  D  and  e  by  partially  clamp- 


IllllillllllilllllllllllllllllllllllllJ 

iiniiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiii' 

i     \ 

h       1 

ing  the  tube  at  this  point  (Fig.  379).  The  continuity  of  the  fall  of  pres- 
sures in  the  vertical  tube  is  at  once  abolished.  Between  a  and  d  there  is 
a  continuous  fall,  which  is  succeeded  by  a  steep  fall  between  D  and  e, 
and  this  again  by  a  gradual  fall  between  E  and  G.  In  any  system  of 
tubes  therefore  through  which  fluid  is  flowing  the  fall  of  pressure 
between  any  two  points  will  be  proportional  to  the  velocity  of  the  flow 
between  these  two  points.  The  velocity,  on  the  other  hand,  will  vary 
directly  as  the  difference  of  pressures,  and  inversely  as  the  resistance 
between  the  two  points,  which  may  be  expressed  by  the  formula 

In  the  vascular  system,  while  the  circulation  is  maintained,  the 
largest  difference  of  pressure  exists  between  the  arteries  on  the  one 
side  and  the  small  veins  on  the  other,  a  great  fall  occurring  between  the 
arteries  and  the  capillaries  themselves.  This  distribution  of  pressure 
points  to  the  chief  resistance  in  the  vascular  system  as  being  situated  m 
the  arterioles.  The  resistance  presented  by  these  vessels  is  due  to  the 
fact  that  they  are  maintained  in  a  state  of  tonic  contraction  by 
the  agency  of  the  central    nervous    system.     The  total  bed  of  the 


992  PHYSIOLOGY 

stream  in  the  region  of  the  arterioles,  while  greater  than  that  of 
the  arteries,  is  considerably  less  than  that  of  the  rich  meshwork 
of  capillaries,  while  the  difference  between  the  diameters  of  arte- 
rioles and  capillaries  is  not  very  great.  On  this  account  the 
velocity  of  the  blood  in  the  arterioles  is  very  much  greater  than  that 
obtaining  in  the  capillaries,  and  since  friction  and  therefore  the  resist- 
ance varies  as  the  square  of  the  velocity,  the  resistance  to  the  flow  of 
blood  through  the  arterioles  must  be  much  greater  than  that  presented 
by  the  capillaries.  The  large  part  taken  by  the  arterioles  in  deter- 
mining the  difference  of  pressure  between  the  arteries  and  veins  is 
shown  by  the  fact  that  this  difference  can  be  diminished  to  one  half 
by  any  means  which  causes  a  dilatation  of  the  arterioles,  as,  for  example, 
destruction  of  the  vasomotor  centre. 

THE  CONVERSION  OF  AN  INTERMITTENT  INTO  A 
CONSTANT  FLOW 
^  Not  only  is  the  blood  pressure  in  the  veins  much  lower  than  in  the 
arteries,  but  the  flow  of  blood  has  been  converted  on  its  passage  through 
the  peripheral  resistance  from  a  pulsatory  into  a  continuous  flow. 
This  change  is  connected  with  the  distensible  elastic  nature  of  the 
arterial  walls. 

Since  this  is  a  purely  mechanical  question  it  will  be  more  easily 
understood  by  a  simple  illustration.  The  heart  may  be  regarded  as 
a  pump,  forcing  a  certain  amount  of  blood  (in  man  about  60  c.c.)  into 
the  circulation  at  each  stroke.  If  a  pump  be  connected  with  a  rigid 
tube,  every  time  that  a  certain  amount  is  forced  into  the  beginning  of 
the  tube  an  exactly  equal  quantity  will  be  forced  out  at  the  other 
end.  Increasing  the  peripheral  resistance  by  partial  closure  of  the 
end  of  the  tube  will  not  affect  the  intermittent  character  of  the  flow, 
but  will  merely  serve  to  diminish  the  quantity  thro^vn  in,  as  well  as  the 
quantity  which  escapes  at  the  other  end  of  the  tube,  supposing  that 
the  work  done  by  the  pump  is  equal  in  both  cases.  If  instead  of  a 
rigid  tube  we  employ  an  elastic  tube  and  the  end  be  left  open  so  that 
no  resistance  is  offered  to  the  outflow  of  the  fluid,  the  effect  will  be 
the  same  as  when  we  used  the  rigid  tube  ;  the  outflow  will  correspond 
exactly  to  the  inflow  and  will  be  just  as  intermittent.  But  now,  if 
the  end  of  the  elastic  tube  be  clamped  so  as  to  increase  the  resistance 
to  the  outflow,  there  will  be  a  marked  difference  from  the  results 
obtained  when  the  rigid  tube  was  partially  obstructed.  Each  stroke 
of  the  pump  forces  a  certain  amount  of  fluid  into  the  tube.  Owing 
to  the  peripheral  resistance  this  cannot  all  escape  at  once,  and  so  part 
of  the  force  of  the  pump  is  spent  in  distending  the  walls  of  the  tube, 
and  part  of  the  fluid  that  was  forced  in  remains  in  the  tube.  The 
distended  elastic  tube  tends  to  empty  itself  and  forces  out  the  fluid 


THE  BLOOD  PRE88URE  993 

which  over-distends  it  before  the  next  stroke  of  the  pump  occurs. 
So  now  the  outflow  may  be  divided  into  two  parts,  one  part  which  is 
forced  out  by  the  immediate  effect  of  the  stroke  of  the  pump,  and 
another  part  which  is  forced  out  by  the  elastic  reaction  of  the  tube 
between  the  strokes.  If  the  strokes  be  rapidly  repeated  before  the 
tube  has  time  to  empty  itself  thoroughly,  it  will  get  more  and  more 
distended.  Greater  distension  means  stronger  elastic  reaction,  and 
therefore  stronger  outflow  of  the  fluid  between  the  beats.  This  dis- 
tension goes  on  increasing  till  the  fluid  forced  out  between  the  strokes 
by  the  elastic  reaction  of  the  wall  of  the  tube  is  exactly  equal  to  that 
entering  at  each  stroke,  and  the  flow  thus  becomes  continuous. 

The  same  thing  occurs  in  the  living  body.  A  man's  heart  at  each 
beat  or  contraction  forces  about  60  c.c.  of  blood  into  the  already  dis- 
tended aorta.  The  first  effect  of  this  is  to  distend  the  aorta  still 
further.  The  elastic  reaction  of  the  walls  drives  on  another  portion 
of  blood,  which  distends  the  next  segment  of  the  arterial  wall,  and  so 
the  wave  of  distension  is  transmitted  with  gradually  decreasing  force 
along  the  arteries.  This  wave  of  distension  is  what  we  feel  on  the 
radial  artery,  or  any  exposed  artery,  as  the  pulse.  After  each  heart- 
beat the  arteries  tend  to  return  to  their  original  size,  and  drive  the 
blood  on  through  the  arterioles  (the  peripheral  resistance)  into  the 
capillaries  and  so  into  the  veins.  By  the  time  the  blood  has  reached 
the  veins  all  trace  of  the  heart-beat  has  disappeared  and  the  pressure 
has  fallen  to  a  few  millimetres  of  mercury. 


INFLUENCE  OF  THE  CAPACITY  OF  THE  VASCULAR  SYSTEM 
ON  THE  CIRCULATION 
So  far  we  have  only  considered  the  influence  of  changes  of  pres- 
sure and  resistance  in  a  system  of  tubes  with  a  head  of  pressure 
at  one  end  and  a  free  outflow  at  the  other.  In  the  body,  however,  the 
vascular  system  is  a  closed  circuit  of  elastic  tubes  presenting  varying 
resistances  to  the  flow  of  blood,  and  of  varying  distensibility  at  different 
parts  of  their  course.  In  this  closed  system  is  inserted  a  pump,  the 
heart,  with  the  function  of  driving  the  blood  through  the  system. 
Since  all  the  blood-vessels  are  elastic  and  distensible  the  capacity  of 
the  system  is  not  fixed,  but  nmst  vary  with  the  internal  pressure  to 
which  the  vessels  are  subjected.  Moreover  the  position  of  the  dif- 
ferent parts  of  the  circulation  must  have  an  influence  on  the  capacity 
of  the  system,  since  the  dependent  vessels  will  be  distended  not  only 
by  the  average  pressure  of  the  fluid  throughout  the  system  but  also 
by  the  hydrostatic  pressure  due  to  the  w^eight  of  the  column  of  fluid 
pressing  on  them.  The  elasticity  of  the  tubes  is  also  a  varying  factor 
and  can  be  considerably  altered  by  the  contraction  of  the  muscular 

U3 


994 


PHYSIOLOGY 


coats  of  the  vessels,  or  by  pressure  on  the  vessels  exerted  by  the  sur- 
rounding muscular  and  elastic  structures. 

It  will  simplify  the  discussion  of  the  main  factors  of  the  circulation 


Fig.  380.     Artificial   schema    to   demonstrate  the  main   features    of   the 

circulation. 
The  heart  is  an  enema  syringe  with  valves  at  V  and  V.  The  artery  is  a 
thick- walled  rubber  tube.  On  the  venous  side  is  placed  a  length  of  wide 
thin-walled  tubing,  to  represent  the  large  tliin-walled  distensible  veins.  The 
arterioles  and  capillaries  (peripheral  resistance)  are  represented  by  wide  glass 
tubes  packed  with  sponges.  By  opening  the  clamp  on  the  tube  d  ('  splanchnic 
area  arterioles  ')  the  peripheral  resistance  can  be  removed,  and  a  free  passage 
of  fluid  allowed  from  arterial  to  venous  side. 


in  a  closed  system  if,  for  the  present,  we  neglect  the  variable  factors 
and  see  what  would  take  place  in  such  a  system  of  elastic  tubes  all 
situated  on  one  horizontal  plane.     Such  a  system  is  represented  in  the 

diagram  (Fig.  381),  and  a  working  model  of 
it  in  Fig.  380. 

The  heart  H  is  interpolated  at  one  part 
of  the  circuit,  while  the  free  outflow  of  the 
fluid  from  b  to  d  is  impeded  by  the  presence 
of  a  peripheral  resistance  at  c.  Such  a 
system  would  have  a  definite  capacity  at 
zero  internal  pressure,  but  a  very  much 
greater  amount  of  fluid  might  be  forced  into 
it  under  a  positive  pressure.  We  will  assume 
that  the  pressure  throughout  the  system  is 
equal  to  10  mm.  Hg,  i.e.  the  elastic  tubes  are  all  slightly  distended. 
If  the  heart  h  now  begins  to  contract  it  will  pump  fluid  from  e  into  a. 
The  pressure  in  e  will  fall  from  10  mm.  to  0  mm.,  while  that  in  A  will 
rise  to  a  corresponding  extent,  the  resistance  at  c  preventing  the  free 
escape  of  fluid  from  b  to  d  and  so  causing  the  heart  to  pile  up  the 
fluid  which  it  has  taken  from  e  into  a. 


THE  BLU(JD  PRESSURE  995 

If  the  texture  of  the  tubes  were  uniform  throughout  the  system 
it  is  evident  that  the  rise  of  pressure  in  a  would  approximate  very 
nearly  to  the  fall  of  pressure  in  E.  In  the  vascular  system  the  veins 
are,  however,  much  more  easily  distended  than  the  arteries.  In 
Fig.  369  (p.  982)  is  shown  the  distensibility  of  corresponding  sections  of 
arteries  and  veins  under  gradually  increasing  internal  pressures.  An 
artery  has  a  certain  capacity  even  at  zero  pressure.  As  the  pressure  in 
its  interior  is  increased  the  artery  is  distended,  and  its  capacity  rises  first 
slowly  and  then  more  rapidly,  the  increment  in  capacity  being  greatest 
between  90  and  110  mm.  Hg.  The  vein,  on  the  other  hand,  is  collapsed 
when  there  is  no  distending  force  in  its  interior,  so  that  at  zero  pressure 
its  capacity  is  nothing.  The  slightest  rise  of  pressure,  even  of  1  mm.  Hg. 
causes  a  considerable  increase  in  its  capacity,  and  the  capacity 
rises  rapidly  with  increasing  pressure  up  to  about  20  mm.  Hg.  Whereas 
the  artery  is  most  distensible  at  100  mm.,  the  vein  is  at  its  optimum 
distensibility  at  about  10  rtim.  Hg.  If  therefore  the  tubes  at  e  are 
made  of  thin-walled  rubber  tubing  they  will  be  considerablv  dis- 
tended under  a  pressure  of  10  mm.  Hg.,  which  has  practically  no 
influence  on  the  thicker-walled  arterial  tube  a. 

A  small  amount  of  fluid  taken  from  E  would  cause  very  little  fall 
of  pressure  on  this  side.  A  considerable  force  will  be  necessary  to  send 
this  fluid  into  the  more  resistant  arterial  tube,  so  that  on  pumping  a 
given  amount  of  fluid  from  e  to  A  the  pressure  in  e  may  fall  5  mm., 
while  the  pressure  in  a  has  to  be  raised  from  50  to  100  mm.  Hg.  in 
order  to  distend  the  arteries  to  such  an  extent  that  they  will  accom- 
modate the  fluid  taken  from  e. 

In  such  a  system,  when  the  heart  is  at  rest,  the  pressure  all  over  the 
system  will  be  uniform,  and  in  the  example  we  have  chosen  the  mean 
systemic  pressure  was  10  mm.  Hg.  When  the  heart  contracts  it  takes 
up  fluid  from  the  venous  side  and  piles  it  up  on  the  arterial  side  mitil 
the  pressure  on  the  arterial  side  is  sufl&cient  to  cause  exactly  the  same 
amount  of  fluid  to  flow  through  the  peripheral  resistance  into  the  veins 
as  is  taken  by  the  heart  from  the  veins  at  each  beat.  This  rise  of  pressure 
in  the  arteries  may  be  many  times  greater  than  the  fall  of  pressure  in 
the  veins.  If  more  fluid  is  injected  into  the  syst^em  when  the  heart  is  at 
rest  the  whole  system  will  be  more  distended  and  the  mean  systemic 
pressure  will  rise.  When  the  heart  contracts  it  will  raise  the  pressure  on 
the  arterial  side  and  lower  that  on  the  venous  side  as  before,  but  it  is 
evident  that  according  to  the  force  of  the  heart-beat  the  arterial 
pressure  may  be  less  than,  equal  to,  or  greater  than  the  pressure 
attained  before  the  introduction  of  fluid.  Since,  however,  the  mean 
systemic  pressure  is  raised,  the  increased  amount  of  fluid  must  be  accom- 
modated somewhere,  so  that  if  the  arterial  pressure  is  as  great  as 
before,  the  venous  pressure  must  be  greater.     In  the  same  way  the 


996  PHYSIOLOGY 

withdrawal  of  a  certain  amount  of  fluid  may  lower  the  mean  systemic 
pressure,  say  from  10  to  5  mm.  Hg.  It  is  still  possible  for  the  pump 
to  maintain  an  arterial  pressure  equal  to  that  produced  when  the 
mean  systemic  pressure  was  10  mm.  Hg,  but  to  produce  this  effect 
the  relative  distribution  of  blood  must  be  altered  and  the  veins  must 
be  more  empty  than  they  were  previously.  The  maintenance  of  a 
constant  arterial  pressure  with  varying  amount  of  fluid  in  the 
system  can  therefore  be  accomplished  either  by  alterations  in  the 
work  of  the  heart  or  by  alterations  in  the  peripheral  resistance,  and 
therefore  in  the  ease  with  which  the  blood  is  allowed  to  escape  from 
the  arterial  to  the  venous  side. 

Alterations  of  the  capacity  of  the  system  will  have  the  inverse 
efiect  to  alterations  of  its  contents.  Thus  diminution  in  the  volume 
of  veins,  such  as  might  be  caused  in  the  living  body  by  the  contrac- 
tion of  their  walls  and  which  may  be  imitated  in  our  model  by  pressure 
on  the  veins  from  without,  will  drive  the  fluid  into  other  parts  of  the 
system  and  therefore  raise  the  mean  systemic  pressure.  If  the  heart 
is  contracting  the  result  may  be  a  rise  of  pressure  all  round  the  system, 
both  in  arteries  and  veins,  or  the  rise  may  be  confined  to  the  arteries 
bv  increased  action  of  the  heart,  or  it  may  be  confined  to  the  veins  by 
diminished  action  of  the  heart  and  increased  constriction  of  the 
arterioles  forming  the  peripheral  resistance. 

Similar  change  in  capacity  may  be  brought  about  if  we  bring  in  the 
effects  of  hydrostatic  pressure.  If  in  the  model  illustrated  (Fig.  380) 
we  allow  the  thin-walled  vein  to  hang  over  the  edge  of  the  table  the 
pressure  of  the  column  of  fluid  within  it  causes  it  to  dilate  and  there- 
fore to  accommodate  more  fluid,  and  this  increased  capacity  might 
be  so  great  that  the  pressure  in  the  section  of  the  vein  near  the  heart 
might  sink  to  nothing  and  the  heart  receive  no  blood  when  it  started  to 
contract.  The  whole  arterial  system  might  in  this  way  be  allowed  to 
drain  under  the  influence  of  gravity  into  the  distensible  dependent 
segment  of  the  venous  tube. 

All  the  conditions  in  our  artificial  schema  have  their  exact 
analogue  in  the  living  body.  The  determination  of  the  mean  systemic 
pressure  in  the  living  body  is  difficult  to  carry  out  with  accuracy.  If, 
for  instance,  we  stop  the  heart,  which  we  can  do  by  stimulation  of  the 
vagus  nerve,  the  arteries  will  gradually  empty  themselves  through  the 
peripheral  resistance  into  the  veins,  and  this  process  will  tend  to  go  on 
until  the  pressures  are  identical  throughout  the  system.  Before  this 
equilibrium  is  arrived  at,  however,  reaction  takes  place  on  the  part  of 
the  animal,  tending  to  restore  the  failing  circulation.  Thus  the 
vessels  contract  strongly,  so  diminishing  the  capacity.  Movements 
take  place  causing  pressure  on  the  veins  of  the  abdomen  and  the  suc- 
tion of  the  blood  into  the  big  veins  of  the  thorax.     Moreover  the  vessels 


THE  BLOOD  PRESSURE  997 

in  an  animal  are  not  all  on  one  plane,  and  if  the  animal  is  in  a  vertical 
position  the  hydrostatic  pressure  of  the  column  of  blood  between 
the  heart  and  the  dependent  parts  of  the  body  may  distend  the  veins 
to  such  an  extent  that  the  whole  of  the  blood  is  taken  up  in  these  veins 
and  none  returned  to  the  heart.  The  fact  that  after  stoppage  of  the 
heart  the  pressure  is  positive  at  all  parts  of  the  vascular  system  in  the 
animal  with  open  thorax  shows  that  there  is  actually  a  mean  systemic 
pressure,  i.e.  under  normal  circumstances,  when  the  animal  is  in 
a  horizontal  position,  all  parts  of  the  system  are  slightly  distended. 
Direct  measurement  shows  that  this  mean  systemic  pressure  is  about 
10  mm.  Hg.  The  smallness  of  this  figure  shows  moreover  that  under 
the  influence  of  gravity  alone  the  pressure  will  be  easily  reduced 
to  nothing  at  all  in  the  upper  parts  of  the  body.  In  a  man  in  the 
vertical  position,  in  the  absence  of  the  nervous  reactive  mechanism 
which  we  shall  consider  later  on,  the  whole  of  the  blood  would  accumu- 
late in  the  abdomen  and  lower  parts  of  the  body,  and  the  circulation 
would  come  to  a  standstill.  On  the  other  hand,  the  pressure  may  be 
altered  in  any  part  of  the  vascular  system  in  any  of  the  following 
ways  : 

(1)  Alteration  of  capacity  of  the  total  system  either  by  contrac- 
tion of  walls  of  the  vessels  or  by  pressure  on  them  from  without. 

(2)  Alteration  of  the  total  volume  of  the  circulating  fluid. 

Either  of  these  two  factors  would  affect  in  the  first  place  the  mean 
systemic  pressure.  The  distribution  of  pressure,  i.e.  the  relative 
pressure  in  the  arteries  and  veins,  will  be  determined  by 

(3)  Alteration  in  the  heart  beat, 

(4)  Alteration  in  the  peripheral  resistance  and  therefore  in  the  ease 
with  which  the  blood  can  escape  from  arterial  to  venous  side. 

In  any  change  either  in  arterial  or  venous  pressure  at  least  two  of 
these  factors  are  involved.  Every  constriction  of  arterioles  causes 
not  only  an  increase  in  the  peripheral  resistance  but  also  a  diminished 
capacity  of  the  whole  system,  so  that  the  arterial  pressure  is  raised  at 
the  same  time  as  the  mean  systemic  pressure.  Nearly  always  such 
a  change  will  involve  as  its  immediate  consequence  some  correspond- 
ing alteration  in  the  heart-beat,  so  that  at  least  three  factors  will 
co-operate  in  the  production  of  the  rise  or  fall  of  blood  pressure.  We 
shall  have  occasion  to  deal  with  many  examples  of  these  complex 
conditions  when  we  are  discussing  the  reactions  of  the  vascular  system 
as  a  whole. 

THE  DEPENDENCE  OF  ARTERIAL  PRESSURE  ON  OUTPUT 

OF  HEART 
The  importance  oi  the  heart-beat  in  determining  arterial  pressure 
is  connected  with  its  output  in  a  given  time.     The  arterial  pressure 


998  PHYSIOLOGY 

is  due  to  the  fact  tliat  the  heart  is  taking  up  fluid  from  the  venous 
side  and  pumping  it  into  the  arterial  side.  The  pressure  on  the  latter 
side  must  rise  so  long  as  the  rate  at  which  the  fluid  is  put  into  the 
arterial  system  by  the  heart  is  greater  than  that  by  which  it  escapes 
through  the  peripheral  resistance.  Arterial  pressure  therefore  is  a 
resultant  of  the  two  effects  : 

{a)  The  amount  of  blood  entering  the  arterial  system  from  the 
heart ; 

(b)  The  amount  of  blood  Jeaving  the  arterial  system  through  the 
peripheral  resistance. 

It  is  evident  that  the  pressure  will  be  altered  by  altering  either  of 
the  two  factors — peripheral  resistance  or  output  of  the  heart.  The 
cardiac  output  will  depend  on  the  amount  of  blood  contained  in  the 
heart  at  the  beginning  of  each  contraction,  on  the  strength  with  which 
the  heart  beats,  and  on  the  number  of  contractions  which  the  heart 
gives  in  any  given  period  of  time.  The  filling  of  the  heart  at  the 
beginning  of  each  beat  is  in  its  turn  dependent  on  the  amount  of 
blood  which  is  available  to  fill  the  cavities  and  therefore  on  the  pressure 
in  the  great  veins.  Increased  frequency  of  heart-beat  need  not  there- 
fore necessarily  increase  the  total  output  of  the  heart  into  the  arterial 
system.  If  the  heart  is  beating  with  optimum  rate  and  force  it  will 
keep  the  venous  system,  at  any  rate  that  part  nearest  the  heart, 
practically  empty,  and  it  is  not  possible  for  it  to  obtain  more  blood 
to  put  into  the  arterial  side,  however  frequently  it  may  beat.  There 
will  be  an  optimum  frequency  of  the  heart-beat  which  will  depend 
on  the  state  of  filling  of  the  great  veins.  The  fuller  these  are  the 
more  rapidly  the  heart  may  beat  without  diminution  of  total  output. 
On  the  other  hand,  in  a  normal  animal  with  the  heart  beating  at  its 
optimum  rate  and  with  effective  contraction  of  its  muscular  walls, 
while  slowing  the  heart-rate  will  diminish  the  total  output  and  therefore 
the  arterial  pressure,  increase  in  the  frequency  of  the  beat  cannot  raise 
the  arterial  pressure  to  any  appreciable  extent,  though  the  heart 
may  tend  to  wear  itself  out  by  beating  at  a  greater  rate  than  the 
optimum. 


SECTION  III 

THE  VELOCITY  OF  THE  BLOOD   AT  DIFFERENT 
PARTS  OF  THE  VASCULAR  SYSTEM 

When  fluid  is  flowing  through  a  tube  of  uniform  diameter,  the 
amount  passing  between  any  two  points  is  practically  in  proportion  to 
the  difference  of  pressure  between  these  two  points,  and  varies 
inversely  as  the  resistance  to  be  overcome.  If  the  tube  is  of  unequal 
bore,  as  represented  in  Fig.  382,  since  the  amount  of  fluid  passing 
a  during  a  given  interval  of  time  must  be  equal  to  the  amount  passing 
6_where  the  bed  of  the  stream  is  wider— the  velocity  of  the  flow 
must  be  smaller  at  6  than 


at  a.    The  same  dependency 

of  velocity  on  the  total  bed , 

must  apply  in    any  closed  "         I - 

system  of  tubes.    Thus  in  a  ^ 

closed  circuit  (Fig.  381)  with 

a  steady  flow  from  the  arterial  to  the  venous  side,  the  amount  of 

fluid  leaving  the  heart  and  passing  a  during    a    minute   must   be 

exactly  equal  to  the  total  amount  of  fluid  passing  from  arteries  to 

veins  through  the  peripheral  resistance  b. 

The  total  area  at  c  is  probably  one  thousand  times  that  of  the 
aorta  at  a,  and  we  should  expect  therefore  a  proportionate  slowing 
of  the  blood-stream.  As  a  matter  of  fact,  while  the  velocity  of  the 
blood  in  the  aorta  of  a  large  animal  may  be  taken  as  about  half  a  metre 
per  second,  the  velocity  of  the  blood  in  the  capillaries  is  about  half 
a  millimetre  per  second.  Moreover,  since  the  total  cross-section  of 
the  big  veins  near  the  heart  under  a  normal  distending  pressure  is 
about  twice  that  of  the  first  part  of  the  aorta,  the  velocity  of  the 
blood  in  the  great  veins  is  only  about  half  of  that  found  in  the  aorta. 
In  such  a  closed  circuit  increased  output  of  the  heart  will  increase 
the  average  velocity  round  the  system,  and  the  same  effect  may  be 
produced  by  diminution  of  the  peripheral  resistance. 

In  the  living  body  a  great  dilatation  of  the  arterioles,  causing  a 
fall  of  the  peripheral  resistance,  generally  increases  the  total  capacity 
of  the  system.  The  arterial  rela.xation  therefore  not  only  gives  rise 
to  an  easier  outflow  from  arteries  to  veins  but  also  causes  a  diminished 
dilatation  of    the  veins  and  therefore  decreased  filling  of  the  heart 

999 


1000  PHYSIOLOGY 

during  diastole.  Tlie  heart  output  is  therefore  also  lessened,  so  that 
a  final  result  of  a  dilatation  of  the  arterioles  may  be  a  diminished  instead 
of  an  increased  velocity  throughout  the  system. 

The  foregoing  discussion  of  the  factors  which  determine  the  average 
velocity  across  a  given  cross-section  of  the  whole  vascular  system 
must  not  be  applied  directly  to  the  changes  in  the  velocity  following 
on  local  alterations  in  the  resistance  presented  by  some  particular 
vascular  area.  In  this  case  the  local  changes  are  insufficient  to  affect 
the  general  arterial  blood  pressure,  and  the  effect  of  diminution  of  peri- 
pheral resistance  is  to  furnish  a  short  cut  for  a  small  portion  of  the 
total  output  of  the  heart  from  the  arterial  to  the  venous  side.  Thus 
dilatation  of  the  vessels  of  the  submaxillary  gland,  while  not  altering 
the  general  blood  pressure  as  registered  in  the  carotid  artery,  causes 
the  blood -flow  through  the  gland  to  be  increased  six  to  eight  times, 
and  the  peripheral  resistance  may  be  so  far  diminished  that  the  blood 
passes  through  the  capillaries  into  the  veins  without  losing  the  pulsa- 
tile force  imparted  to  it  by  each  heart-beat.  The  pressures  therefore 
in  arterioles,  capillaries,  and  veins  are  all  increased  by  this  local  vaso- 
dilatation. On  the  other  hand,  constriction  of  the  arterioles  of  any 
given  part  will  diminish  the  velocity  of  the  blood  through  this  part  and 
also  the  pressure  in  its  capillaries. 

The  larger  the  area  affected  by  the  change  in  the  peripheral 
resistance,  the  more  difficult  it  is  to  predict  a  'priori  what  will 
be  the  result  on  the  velocity  of  the  blood  and  on  the  circulation  as 
a  whole,  or  in  the  parts  specially  affected.  Thus  section  of  one 
splanchnic  nerve  in  the  dog  causes  an  increased  flow  of  urine  from  the 
kidney  on  the  same  side,  the  paralysis  of  the  vessels  in  this  organ 
causing  an  increased  flow  of  blood  through  it  and  an  increased  pressure 
in  its  capillaries.  Section  of  the  corresponding  nerve  of  the  rabbit 
may  cause  a  diminution  rather  than  an  increase  in  the  amount  of 
urine  secreted,  owing  to  the  fact  that  the  total  area  supplied  by  the 
splanchnic  nerve  is  much  greater  relatively  in  the  rabbit  than  in 
the  dog.  Thus  section  of  this  nerve  may  cause  such  a  widespread 
dilatation  that  the  blood  pressure  falls  ;  and  although  the  vessels  in 
the  kidney  are  relaxed,  the  arterial  pressure  is  not  sufficient  to  drive 
through  these  relaxed  vessels  as  much  blood  as  was  previously  driven 
through  the  normally  contracted  arterioles. 

METHODS  OF  MEASURING  THE  VELOCITY  OF  THE  BLOOD 

The  velocity  in  an  artery  is  measured  by  placing  some  apparatus  in  the 
path  of  the  blood  without  intercepting  its  flow  ;  such  an  apparatus  may  be 
used  to  give  the  quick  variations  in  the  velocity  which  occur  in  the  course  of 
each  heart-beat,  or  the  average  flow  of  blood  through  the  cross-section  of  the 
artery  in  a  given  space  of  time.  For  the  latter  purpose  Ludwig's  Stromuhr,  or 
current  clock,  has  been  most  used.     This  instrument  consists  of  two  bulbs  of 


VELOCITY  OF  BLOOD  IN  VASCULAR  SYSTEM      1001 

equal  size,  a  and  b,  communicating  with  one  another  above  ;   their  lower  ends 
are  clamped  in  the  disc  c,  which  is  pierced  by  two  openings  serving  to  connect  the 
lower  orifices  of  the  bulbs  with  the  tubes  t,  t,  cemented 
into  the  lower  disc  ab. 

An  artery  such  as  the  carotid,  being  clamped  at  its 
central  end  and  divided,  a  is  inserted  into  its  central 
end,  and  b  into  its  peripheral  cut  end.  The  tube  a  is 
filled  with  oil  and  b  with  salt  solution  or  dcfibrinated 
blood.  On  clamping  the  artery,  blood  flows  into  a  and 
drives  the  contained  oil  over  into  b,  the  contents  of  b  being 
meanwliile  forced  into  the  peripheral  end  of  the  artery. 
Wlien  blood  has  completely  filled  the  bulb  a,  the  two 
bulbs  are  reversed,  and  the  blood  now  entering  the  artery 
displaces  the  oil  in  b,  and  forces  the  blood  wliich  had 
entered  a  on  into  the  peripheral  end  of  the  artery. 
Knowing  the  capacity  of  the  bulbs  and  the  number  of 
times  it  has  been  necessary  to  turn  tliera  in  the  course, 

Fk;.  383      Dia'Tum   of  ^^J'  ^^  ^^^  minute,  we  know  also  tlie  amount  of  blood 

Liulwig's  '  Stromulir.'    which  has  passed  across  the  section  of  tlic  artery  under 
experiment. 
In  order  to  determine  from  this  volume  the  velocity  of  the  blood  across  the 

section,  i.e.  tlirough  the  artery,  the  total  ^ ^ 

volume  passing  in  the  minute  must  be 

divided   by  the  cross-section.    This  will 

give  the  velocity    per   minute.      Many 

modifications   of    this   apparatus    have 

been  devised.     A  simple  form  of  current 

measurer   is   shown   in  Fig.    384.     The 

whole  apparatus  is  constructed  of  glass. 

The  tube  a  is  connected  with  tlie  central  from  ^rjery 

end   of  a  cut  artery,   and  the   tube   p    " 

with  the  peripheral  end.    The  blood  flows 

into  B  and  fills  it.     As  soon  as  it  is  full 

and  its  level  rises  over  the  level  of  the 

bend  of  tlie  siplion  tube  s,  the  blood  is 

rapidly  siphoned  off  into   c,   whence  it 

flows  along  p  into  the  peripheral  part 

of  the  artery.    The  side  tube  R  is  con- 
nected  with  a  mercury  or    membrane 

manometer.       Every    time    that    B    is 

emptied  into  c  a  depression  is  produced 

on  the  manometer  tracing,  which  thus 

records   not  only  the  average   pressure 

but  also  the  average  velocity  of  the  blood 

in  tlie  artery.     Each  instrument  has  to 

b(^    calibrated    in   order   to    know   how 

much  blood    passes   from  B   to    c  each 

time  that  siphonage  occurs. 

None  of  these  methods  give  any  in- 
formation *)f  any  rapid  changes  occurring 

in  the  velocity  of  the  blood,  e.g.  during 

a  single  pulse-wave.    For  this  purpose  we 

must  have  recourse  to  some  instrument      Pi,;.  :{S4.     A  simple  hlood-eiirront  mmsunT. 

such  as  Cliauveau's  luemadromograph  or  (Ishikawa  and  Stakmni:.) 


1002 


PHYSIOLOGY 


Cybulski's  photohaematachometer.  The  hcemadromograph  (Fig.  385)  consists 
of  a  pendulum  which  is  hung  in  a  tube,  tlirough  which  the  blood  is  allowed  to 
flow,  placed  in  the  course  of  the  artery.  The  deviation  of  this  pendulum  from 
the  vertical  -nail  be  in  proportion  to  the  velocity  of  the  current,  and  if  its  upper 
end  be  connected,  as  in  the  diagram,  with  a  tambour,  the  variations  in  velocity 
can  be  recorded  on  a  blackened  surface  by  means  of  a  lever.  The  photohcemata- 
clwmeter  is  based  on  an  interesting  appUcation  of  Pitot's  tubes.  If  a  current  of 
blood  be  directed  along  the  tube  ah  possessing  two  vertical  side  tubes  c  and  d 
(Fig.  386),  the  pressure  at  c  ^^dU  be  greater  than  that  at  d,  since  at  c  the  momentum 


A 


n 


pi 


Fig.  38.5.  Diagram  showmg  the 
construction  of  Chauveau's 
haemadromograph. 


Fig.  386.  Diagram  to  show  principle  of 
construction  of  Cybulsld's  photo-haemata- 
chometer. 


of  the  moving  mass  of  blood  is  added  to  the  lateral  pressure  of  the  fluid.  A  tube 
of  tliis  shape  is  connected  with  an  artery,  such  as  the  carotid,  and  the  tubes 
h  and  h'  are  attached  at  the  points  c  and  d.  These  two  tubes  are  united  at  their 
upper  extremities.  In  tliis  case  so  long  as  the  blood  flows  from  a  to  6  the  fluid 
in  h  -will  rise  higher  than  in  h\  and  the  difference  in  height  of  the  fluid  in  the 
two  tubes  will  be  proportional  to  the  velocity  of  the  blood.  A  graphic  record  of 
this  difference  of  pressure  is  obtained  by  allowing  a  narrow  beam  of  light  to  throw 
an  image  of  the  menisci  of  the  two  columns  of  fluid  through  a  slit  on  to  a  moving 
photograpliic  plate.  Such  a  record  is  given  in  Fig.  387.  The  width  of  the  black 
space  at  any  point  is  proportional  to  the  velocity  of  the  blood  at  the  moment 
at  which  tliis  part  of  the  record  was  being  taken.  Of  course  this  instrument  has 
to  be  caUbrated  if  we  wish  to  determine  the  velocity  of  the  blood  in  absolute 
measure.  In  Fig.  387  the  velocity  at  the  points  1  and  1',  corresponding  to  the 
cardiac  systole,  was  248  mm.  per  second.     At  2  and  2',  corresponding  to  the 


VELOCITY  OF  BLOOD  IN  VASCULAR  SYSTEM       1003 

dicrotic  elevation,  the  velocity  was  also  248  mm.    At  3  and  3',  towards  the  end 
of  diastole,  the  velocity  sank  to  127  mm. 

The  velocity  of  the  blood  in  the  capillaries  can  be  measured  by  direct  observa- 


FiG.  387.     Record  of  blood-velocity  in  the  carotid  artery 
of  the  rabbit.     (Cybolski.) 

tion  of  the  capillaries  under  the  microscope,  and  noting  the  time  it  takes  for  a 
blood-corpuscle  to  move  from  one  edge  of  the  field  to  the  other. 


THE  VELOCITY  IN  DIFFERENT  PARTS  OF  THE  VASCULAR 

SYSTEM 
During  systole  the  velocity  of  the  blood  in  any  part  of  the  arterial 
system  must  be  greater  than  during  diastole  ;    thus  in  the  carotid 
of  the  horse  the  follo^-incr  fiofiires  were  found  : 


During  systole 
During  diastole 


Velocity  per  second 
520  mm. 
.     150  mm. 


The  following  figures  have  been  obtained  from  experiments  on 
dogs  (Tigerstedt)  : 


Body 
weight 

Artery 

Volume 
per  second 

Linear 

velocity  per 

second 

Diameter 
of  artery 

B.P. 

Remarlcs 

kg. 

14-G 
141 

Criu-al. 

Crural. 
Carotid. 

c.c. 
0-63 

1-69 
1-95 

mm. 
128 

275 
241 

mm. 
2-5 

2-8 
3-3 

mm.Hg. 

77 

88 
93 

Nerves  un- 

injiu-ed 
Nerves  cut 
Nerves  un- 
injured 

SECTION  IV 

THE  MECHANISM  OF  THE  HEART  PUMP 

In  the  mammal  the  two  sides  of  the  heart  are  only  in  communica- 
tion by  means  of  the  blood-vessels  of  the  systemic  and  pulmonary 
area.  Each  side  consists  of  an  auricle  into  which  the  veins  open, 
and  a  ventricle  which  receives  the  blood  from  the  auricle  and  dis- 
charges it  into  the  arterial  trunk — either  aorta  or  pulmonary  artery. 
Since  the  auricles  have  to  act  merely  as  a  receptacle  for  part  of  the 
blood  which  enters  during  the  relaxation  or  diastole  of  the  heart,  their 
cavities  are  smaller  than  those  of  the  ventricles,  and  their  walls  are 
thin,  corresponding  to  the  small  amount  of  work  thrown  on  them 
in  propelling  blood  into  the  relaxed  ventricle.  The  ventricles  have 
the  office  of  carrying  on  the  main  work  of  the  circulation  and  of  forcing 
blood  through  the  peripheral  resistance.  Their  walls  are  much 
thicker  than  those  of  the  auricles.  The  right  ventricle  has  a  wall 
which  is  only  about  one-fourth  the  thickness  of  the  left  ventricle,  in 
conformity  with  the  much  heavier  work  to  be  done  by  the  latter. 
On  cutting  a  section  through  the  two  ventricles  in  a  contracted  con- 
dition the  thin  wall  of  the  right  ventricle  is  seen  to  lie  in  the 
form  of  a  crescent  round  the  circular  left  ventricle.  The  capacity 
of  both  ventricles  is  approximately  equal,  and  amounts  in  man  to 
about  140  c.c.  for  each  ventricle  when  the  heart  is  completely 
relaxed. 

The  auricles  are  separated  from  the  ventricles  by  a  fibrotend.inous 
ring.  From  this  ring  take  origin  most  of  the  muscular  fibres  of  the 
heart  walls.  The  muscular  fibres  of  the  auricles  run  in  both  circular 
and  longitudinal  directions,  the  circular  fibres  being  continued  round 
both  amides,  and  special  rings  of  circular  fibres  surrounding  the 
openings  of  the  great  veins.  From  the  fibrotendinous  ring  between  the 
auricle  and  the  left  ventricle  and  from  the  sides  of  the  aorta  the 
muscular  fibres  forming  the  superficial  layer  of  the  ventricular  wall 
pass  obliquely  downwards  to  the  left  towards  the  apex  of  the  ventricle. 
Here  they  loop  round  into  the  interior  of  the  ventricle  and  pass  up 
near  its  inner  surface  to  end  either  in  the  papillary  muscles  or  in  the 
auriculo-ventricular  ring  of  fibrous  tissue.  Between  these  two  layers 
we  find  a'  third  median  layer  of  muscular  fibres  which  is  in  the  form 
of  a  muscular  cone.     The  fibres  of  this  layer  form  complete  loops  round 

1004 


THE  MECHANISM  OF  THE  HEART  .PUMP  KKJo 

the  left  ventricle.     The  middle  layer  is  connected  by  many  strands  of 
muscular  fibres  with  both  inner  and  outer  layers. 

Mall  divides  the  muscular  fibres  of  the  mammalian  heart  iiil<j  f(mr  groups, 
two  superficial  and  two  deep,  as  follows  : 

(1)  The  superficial  bulbo-spiral  fibres.  These  arise  from  the  conns  arteriosiis, 
the  left  side  of  the  aorta   and  the  left  side  of  the   am-ieulo-ventricular  ring, 


Fig.  388.     View  of  the  heart  from  behind,  to  show  the  course  of  the  chief 
strands  f)f  inu.scle  fibres.     (Mall.) 
The  black  lines  represent  the  bulbo-spiral  fibres,  the  grey  lines  the  sino- 
spiral  fibres. 

and  take  an  oblique  course  to  the  apex,  whi-re  they  make  a  spiral  turn  (tlu-  vortex) 
and  reach  the  interior  of  the  left  ventricle,  ending  for  the  most  part  hi  the  intra- 
ventricular septum  and  the  papillary  muscles. 

(2)  The  superficial  sino-spiral  fibres  rise  on  the  dorsal  side  of  the  heart  from 
the  riglit  auriculo-ventricular  ring  and  run  obliquely  on  the  anterior  surface  of 
the  right  ventricle  to  the  apex,  where  they  also  turji  inwards,  forming  the  anterior 
horn  of  the  '  vortex,'  and  end  chiefly  in  the  papillary  muscles  of  the  right 
ventricle. 

(3)  The  deep  bulbo-spiral  fibres  form  a  complete  cylinder  aroiuid  the  left- 
ventricle,  and  ;ire  attached  chietly  to  the  dorsal  side  of  the  aorta. 

(4)  The  deep  aino-spiral  fibres  aro  attached  to  the  dorsjil  aspect  of  the  left 
aiuiculo-ventricular  ring,  whence  they  enter  the  right  ventricle  and  turn  upwards 


1006  PHYSIOLOGY 

towards  the  base.    The  uppermost  of  these  fibres  form  circular  rings  round  the 
conus  arteriosus  at  the  base  of  the  pulmonary  artery. 

The  fact  that  the  muscular  fibres  are  continuous  over  both  auricles 
and  over  both  ventricles  respectively  ensures  the  practically  simul- 
taneous contraction  of  each  of  these  parts  of  the  heart.  Although 
on  coarse  dissection  there  seems  to  be  absolute  division  between 
the  muscular  tissue  of  auricles-  and  ventricles,  it  has  been  shown 
by  Kent,  His,  and  others  that  there  is  continuity  of  muscular  tissue 
between  the  two  parts  of  the  heart  by  a  special  band  of  muscular 
fibres,  'the  bundle  of  His,'  which  rises  in  the  wall  of  the  right 
auricle  and  passes  beneath  the  foramen  ovale  and  across  the  auriculo- 
ventricular  junction  into  the  inter-ventricular  septum.  The  exact 
course  of  these  fibres  and  their  significance  will  be  considered  later. 
The  normal  direction  of  the  blood-flow  through  the  heart  is  deter- 
mined mainly  by  the  valves  which  guard  the  auriculo-ventricular 
orifices  and  the  openings  of  the  aorta  and  pulmonary  artery.  The  auriculo- 
ventricular  valves  are  tubular  membranes  attached  round  the  entire 
circumference  of  the  auriculo-ventricular  ring.  They  are  composed  of 
fibrous  and  elastic  tissue,  covered  on  each  side  with  endocardium,  and 
project  downwards  into  the  cavities  of  the  ventricles.  On  each 
side  the  membrane  is  divided  by  deep  incisions,  into  large  flaps,  three 
in  number  on  the  right  side  (the  tricuspid  valves)  and  two  in  number 
on  the  left  side  (the  mitral  valves).  The  sail-like  margins  of  these 
valves  are  connected  by  thin  tendinous  cords  to  the  papillary  muscles, 
which  are  nipple-shaped  projections  of  the  muscular  walls  of  the 
ventricles.  By  this  means  the  edges  of  the  valves  are  kept  close 
together  and  prevented  from  eversion  under  the  strong  pressure 
exerted  by  the  contracting  ventricle.  By  the  downward  pull  of  the 
papillary  muscles  on  the  valves  during  the  contraction  of  the  ventricles, 
closure  is  rendered  more  complete,  the  inner  surface  of  the  valves 
being  apposed  over  a  considerable  area.  The  action  of  the  valves 
is  aided  by  the  contraction  of  the  fibres  surrounding  the  base  of  the 
heart,  so  that  the  auriculo-ventricular  orifice  is  much  smaller  during 
systole  than  during  diastole. 

From  a  purely  mechanical  standpoint  the  valves  guarding  the 
arterial  orifices  are  much  more  perfect  than  those  just  described,  which 
depend  for  their  efficiency  on  the  proper  contraction  of  the  ventricular 
wall  and  of  the  musculi  fajnllares.  Each  orifice  is  provided  with  three 
valves,  each  of  which  is  semilunar  in  shape  and  attached  by  its  convex 
borders  to  the  arterial  wall,  and  presents  in  the  middle  of  its  free 
border  a  small  fibro-cartilaginous  nodule,  the  corpus  Arantii,  from 
which  fine  elastic  fibres  pass  to  all  parts  of  the  valve.  The  extreme 
margin  of  the  valve,  the  lunula,  on  each  side  of  the  corpus  Arantii 
is  very  thin,  being   formed   of   little   more   than  the  endocardium. 


THE  MECHANISM  OF  THE  HEART  PUMP 


1007 


Whenever  the  pressure  in  the  arteries  is  greater  than  that  in  the 
ventricles,  these  valves  are  closed,  and  the  thin  margins  come  in  con- 
tact with  similar  portions  of  the  adjacent  valves,  so  preventing  the 
reflux  of  a  single  drop  of  blood.  The  borders  of  the  valves  under 
these  circumstances  come  together  in  the  form  of  a  star  composed  of 


Fuji.  38U.  Left  auricle  and  vcntiiik'.  with  ouUr  side  tut  away  to  show  chief 
pouits  in  anatomy  of  heart.  (Testut.) 
1,  aorta  ;  2,  pulmonary  artery  ;  3,  ant.  coronary  vessels  ;  5,  5',  pulmonary 
veins  ;  6,  left  auricle  ;  7,  auricular  appendage  ;  10,  cavity  of  left  ventricle  ; 
11,  12,  mitral  valves  ;  13,  14,  papillary  muscles  ;  16,  arrow  pointing  to  aortic 
orifice. 

three  lines  at  angles  of  120°,  the  three  corpora  Arantii  being  pressed 
together  at  the  centre  of  the  star. 

No  valves  are  found  at  the  orifices  of  the  great  veins  into  the  auricles,  i 
a  reflux  of  blood  in  this  situation  during  contraction  of  the  heart 
being  prevented  by  the  contraction  of  the  muscular  rings  round  the 
veins,  which  always  accompanies  the  auricular  contraction. 

The  heart  and  the  roots  of  the  great  vessels  lie  almost  free  in  a 
special  cavity,  the  wall  of  which  is  formed  by  a  tough  fibrous  mem- 
brane, the  pericardium.     This  is  attached  below  to  the  central  tendon 


1008  PHYSIOLOGY 

of  the  diaphragm,  and  above  to  the  arterial  trunks.  It  is  lined  by  a 
layer  of  endothelium  continuous  with  a  similar  layer  covering  the 
surface  of  the  heart.  The  two  surfaces  are  kept  continually  moist 
by  the  pericardial  fluid,  so  that  the  heart  can  move  freely  within  the 
pericardium  without  friction.  One  of  the  chief  functions  of  the  peri- 
cardium appears  to  be  to  check  an  excessive  dilatation  of  the  heart 
during  conditions  attended  by  a  great  rise  of  venous  pressure. 

THE  SEQUENCE  OF  EVENTS  IN  THE  CARDIAC  CYCLE 

On  opening  the  chest  of  an  anaesthetised  animal,  while  artificial 
respiration  is  maintained,  the  heart  is  seen  contracting  rhythmically 
within  the  pericardium.  On  incising  this  sac  its  restraining  power 
on  the  dilatation  of  the  heart  is  shown  by  the  fact  that  during  diastole 
the  wall  of  the  heart  bulges  through  the  opening,  and  the  increased 
diastolic  filling,  consequent  on  the  removal  of  this  restraining 
influence,  is  at  once  apparent,  if  in  any  way  the  frequency  of  the  con- 
tractions of  the  heart  be  diminished  so  as  to  prolong  the  diastolic 
period. 

Each  beat  of  the  heart  begins  by  a  simultaneous  contraction 
of  both  auricles  associated  with  a  retraction  of  the  auricular 
appendages,  which  become  pale  and  bloodless.  After  a  pause  of 
not  more  than  a  tenth  of  a  second  the  contraction  of  the  auricles 
is  followed  by  that  of  the  ventricles,  and  blood  is  thrown  out 
into  the  large  arteries.  The  contraction  of  the  auricles  lasts  about 
a  tenth  of  a  second,  that  of  the  ventricles  about  three- tenths  of  a 
second.  The  period  of  relaxation  or  diastole  lasts  about  four-tenths 
of  a  second.  During  this  cycle  of  changes  the  following  events  are 
taking  place  within  the  heart  : 

In  the  diastolic  period  the  aortic  valves  are  closed  and  the  arterial 
system  is  opened  only  towards  the  capillaries.  In  consequence  of 
the  high  pressure  established  within  the  arteries  by  the  previous 
heart-beats  the  blood  flows  steadily  through  the  arterioles,  capil- 
laries, and  veins  into  the  right  heart,  and  similarly  the  pressure 
in  the  pulmonary  artery  causes  a  partial  emptying  of  this  vessel  with 
its  branches  through  the  pulmonary  capillaries  into  the  left  heart. 
The  flow  into  the  heart  is  assisted  by  the  elastic  retraction  of  the  lungs, 
which  causes  a  negative  pressure  in  the  structures  between  them  and 
the  chest  wall,  so  that  the  blood  is  sucked  from  the  other  parts  of  the 
body  towards  the  thorax.  During  diastole  there  is  a  continuous  flow 
of  blood  from  veins  into  auricles  and  from  auricles  into  ventricles,  and 
as  the  walls  of  both  these  cavities  are  relaxed  there  is  no  impediment 
to  the  inflow  of  the  blood  until  the  dilating  heart  begins  to  stretch 
the  pericardium. 

Under  normal  circumstances  the  diastole  comes  to  an  end  before 


THE  MECHANISM  OF  THE  HEART  PUMP  l(jU9 

the  restraining  influence  of  the  pericardium  can  be  efEective.  The  con- 
traction of  the  auricles  drives  their  contents  into  the  ventricles  and  so 
still  further  increases  their  distension,  no  resistance  being  offered  by  the 
widely  dilated  auriculo-ventricular  orifices  or  by  the  flaccid  wall  of  the 
ventricles.  As  the  blood  rushes  from  auricle  into  ventricle  through  the 
funnel-shaped  opening  of  the  membranous  tube  formed  by  the  valves, 
eddies  are  set  up  in  the  ventricle  tending  to  close  the  valves,  so  that  they 
are  held,  as  the  resultant  of  the  two  opposing  currents,  in  a  condition 
midway  between  closure  and  opening.  The  onset  of  the  ventricular 
contraction  is  extremely  rapid.  There  is  a  quick  rise  of  pressure  in 
the  ventricle,  which  presses  together  the  flaps  of  the  mitral  or  tricuspid 
valves,  while  the  bases  of  these  valves  are  approximated  by  the  con- 
traction of  the  circular  fibres  at  the  base  of  the  ventricles.  As  the 
heart  shortens  in  systole  the  papillary  muscles  also  shorten,  so  that 
the  valves  are  drawn  further  down  into  the  ventricles  and  prevented 
from  eversion  into  the  auricles,  while  the  blood  is  pressed,  so  to  speak, 
between  the  cone  of  the  ventricular  wall  and  the  cone  formed  by  the 
tubular  valves. 

The  outflow  of  blood  from  the  ventricles  does  not,  however,  com- 
mence immediately.  Whereas  at  the  beginning  of  systole  the  pressure 
in  the  ventricle  cavity  is  quite  small  (only  2  or  3  mm.  Hg),  there  is  a 
pressure  in  the  aorta  of  50  to  80  mm.  Hg.  Before  the  semilunar 
valves  separating  the  lumen  of  the  aorta  from  the  ventricular  cavity 
can  be  opened,  the  pressure  in  the  left  ventricle  must  rise  to  a  point 
which  is  greater  than  that  in  the  aorta,  and  similarly  on  the  right  side 
of  the  heart.  As  soon  as  this  happens  the  valves  open  and  the  out- 
flow of  blood  commences,  and  continues  so  long  as  the  pressure  in  the 
ventricles  is  higher  than  that  in  the  great  arteries.  Directly,  however, 
the  ventricular  pressure  falls  below  the  arterial  pressure  the  valves  must 
close  and  the  output  of  blood  come  to  an  end. 

In  order  to  obtain  an  accurate  idea  of  the  exact  duration  of  each 
of  these  events  in  the  cardiac  cycle  it  is  necessary  to  study  the  changes 
occurring  in  the  pressure  within  the  auricles  and  ventricles  during  the 
various  phases  of  the  heart-beat. 

THE  ENDOCARDIAC  PRESSURE 
A  manometer  which  shall  register  accurately  the  changes  in  the 
pressure  within  the  heart  must  be  capable  of  responding  to  very 
rapid  changes.  Thus  in  the  left  ventricle  at  the  beginning  of 
the'  systole  there  may  be  a  rise  of  130  mm.  Hg  in  -06  sec,  i.e. 
2170  mm.  Hg  per  second.  A  mercurial  manometer  with  its  great 
inertia  would  be  quite  unequal  to  registering  such  rapid  changes  of 
pressure  and  would  moreover  tend  to  outer  into  oscillations  which  would 
quite  deform  the  curve.     We  require  an  instrument  with  very  small 

64 


1010 


PHYSIOLOGY 


weight  of  moving  parts,  so  as  to  possess  small  inertia  and  be  capable  of 
registering  a  rapid  rise  of  pressure  without  entering  into  oscillations  of 
its  own.  Several  methods  have  been  adopted  for  this  purpose.  In  one 
(Chauveau  and  Marey)  a  cardiac  '  sound  '  (Fig.  390)  is  passed  down  the 


Fig.  390.  Diagram  of  Marey's  cardiac  '  sound,'  consisting  of  a  long  tube 
ab,  terminating  at  one  end  in  the  ampulla  m.,  which  is  covered  with 
an  elastic  membrane.  The  side-piece  c  serves  to  indicate  the  position 
of  the  ampulla  after  it  has  been  iatroduced  into  the  vessels. 

jugular  vein  into  the  right  auricle  or  ventricle,  or  down  the  carotid 
artery  into  the  left  ventricle.  The  cardiac  sound  is  a  stiff  tube  having 
an  elastic  bulb  or  ampulla  at  the  end  which  is  to  be  inserted  into  the 
heart.     The  bulb  is  supported  by  a  steel  frame,  so  that  it  is  not  com- 


FiG.  391.     Mareys  tambour. 
a,  axis  of  lever  ;    b,  metal  tray  covered  with  rubber  membrane,  and  com- 
municating by  tube  /  with  free  end  of  cardiac  sound 

pletely  compressible  by  external  pressure.  The  free  end  of  the  tube  is 
connected  with  a  writing  tambour  (Fig.  391),  a  small  round  metal  tray 
covered  with  a  delicate  elastic  membrane.  To  the  top  of  the  membrane 
a  lever  is  attached  by  which  any  change  of  pressure  on  the  ampulla  may 
be  recorded  on  a  moving  smoked  surface.  The  large  size  of  these 
sounds  makes  it  difficult  to  use  them  on  any  animal  smaller  than  the 


Fig.  392.     Diagram  to  show  construction  of  Hiirthle's  membrane  manometer. 

ass  or  horse.  In  smaller  animals,  such  as  the  dog,  the  question  has 
been  investigated  by  the  use  of  a  manometer  such  as  that  of  Hiirthle. 
In  this  instrument  (Fig.  392)  the  changes  of  pressure  are  recorded  by  the 
oscillations  of  a  thick  rubber  membrane  which  covers  a  very  small  tam- 
bour. The  tambour  is  filled  with  magnesium  sulphate  solution,  which  is 
also  used  to  fill  the  tube  connecting  with  the  heart.    This  tube  can  be 


THE  MECHANISM  OF  THE  HEART  PUMP  1011 

inserted  in  the  same  way  as  Marey's  cardiac  sound.  The  object  of 
making  the  tambour  small  and  the  rubber  membrane  thick  is  to  limit 
the  excursions  as  far  as  possible  and  thereby  diminish  the  total  amount 
of  fluid  moved  with  any  given  rise  of  pressure. 

A  much  more  perfect  form  of  manometer  has  been  devised  by 
Otto  Frank  on  the  basis  of  a  very  complete  investigation  of  the 
theoretical  requirements  of  such  an  instrument.  It  is  evident  that 
the  total  mass  moved  for  the  purpose  of  making  the  record  must 
be  as  small  as  possible,  in  order  to  diminish  the  momentum  of  the 
moving  parts  and  therefore  the  tendency  of  the  instrument  to 
enter  into  vibrations  of  its  own,  which  will  add  to  and  deform  the 
changes  of  pressure  which  it  is  sought  to  record.  On  the  other  hand,  if 
the  vibrations  of  the  instrument  be  damped  by  introducing  artificial 


Fig.  393. 

friction,  the  instrument  will  be  impaired  in  its  power  of  responding 
to  quick  changes  of  pressure.  The  vibration  frequency  of  the  instru- 
ment itself  should  therefore  be  so  rapid  that  there  is  no  fear  of 
confounding  any  such  vibrations  with  the  alterations  of  pressure  in 
the  vascular  system.  The  construction  of  Frank's  instrument  is  shown 
in  Fig.  .393.  It  consists  of  a  short  vertical  tube  which  is  prolonged 
at  its  lower  end  into  a  cone  for  connection  wnth  the  arterial  cannula. 
The  tube  b  is  closed  by  a  tap  c,  by  which  any  possible  air  bubbles  can 
be  let  out.  It  is  important  to  avoid  even  the  smallest  air  bubble  in  such 
an  apparatus,  as  well  as  any  rubber  connections,  as  these  mav  undergo 
compression  or  distension  with  changes  of  pressure  and  therefore  slow 
the  vibration  frequency  of  the  instrument  and  distort  the  curves.  The 
apparatus  is  filled  with  liquid  from  a  reservoir  by  the  tube/.  On  the 
narrowed  end  of  e  the  manometer  capsule  is  cemented.  This  is  covered 
with  a  rubber  membrane,  care  being  taken  to  exclude  air  bubbles 
when  the  membrane  is  tied  on.  A  small  stand  is  fixed  on  c  which 
carries  a  metal  fork  g.      The  two  limbs  of  the  fork  ciirry,  one  a  wedge- 


1012 


PHYSIOLOGY 


shaped  depression,  the  other  a  conical  depression  for  the  points  of  a 
small  mirror  holder,  s.  The  third  leg  of  the  mirror  holder  rests 
on  the  middle  of  the  rubber  membrane.  The  mirror  itself  is  1  cm.  in 
diameter.  Any  excursion  of  the  membrane  is  thus  transmitted  to  the 
mirror,  and  the  movements  of  the  latter  are  recorded  by  reflecting  a 
beam  of  light  from  it  through  a  slit 
on  to  a  photographic  paper  fixed  on 
a  kymograph,  which  is  situated  in 
a  dark  room  or  dark  box.  The 
cannula  is  shown  in  Fig.  394.  It  is 
composed  entirely  of  metal,  and  is 
fixed   on   to    the   cone-shaped   ex-  Fig.  394. 

tremity  of  the  manometer,  where  it 

is  held  in  place  by  the  screws  s.  The  vibration  frequency  of  the  moving 
mass  in  this  instrument  is  180  per  second,  and  it  ^\nll  indicate  not  only 
the  rapid 'changes  of  pressure  occurring  in  the  heart  and  blood-vessels 
at  each  beat,  but  also  the  fine  vibrations  which  are  associated  with 
the  heart  sounds.  The  mass  moved  for  a  given  change  of  pressure  is 
smaller  than  in  any  other  instrument  except  the  capillary  mano- 
meter, which  was  devised  by  Bayliss  and  the  author  for  similar 
purposes. 

By  the  introduction  of  a  valve  in  the  tube  leading  from  the  mano- 
meter to  the  heart  it  may  be  used  as  a 
to  manometer  maximum  and  minimum  manometer 
(Fig.  395).  If  the  valve  permits  fluid  to 
go  only  towards  the  heart  the  mano- 
meter will  indicate  the  minimum  pres- 
sure attained  during  the  cardiac  cycle. 
If  it  be  turned  the  other  way  it  will 
indicate  the  maximum  pressure. 

On  registering  the  endocardiac 
pressure  by  means  of  a  manometer 
capable  o'^  recording  the  quick  changes 
in  pressure  that  occur  in  the  ventricle 
with  each  heart-beat,  a  curve  is 
obtained  similar  to  that  shown  in 
Fig.  396.  Before  we  can  interpret 
this  curve  properly  we  must  super- 
pose on  it  another  curve  taken  simul- 
taneously and  representing  the  altera- 
tions of  pressure  occurring  at  the 
beginning  of  the  aorta.  Only  by  the  comparison  of  the  two  curves  is  it 
possible  to  determine  the  exact  points  at  which  the  aortic  valves  open 
and  close.   The  beginning  of  systole  is  marked  often  by  a  small  rise  in 


max. valve 


to  heart 

Fig.  395.     V.  Frank's  valve. 

This  is  placed  in  the  course  of 
the  tube  between  heart  and  mano- 
meter, so  that  the  latter  maj^  be 
used  as  a  maximum,  minimum, 
or  ordinary  manometer,  according 
to  the  tap  which  is  left  open. 


THE  MECHANISM  OF  THE  HEART  PUMP 


1013 


the  intraventricular  pressure,  due  to  the  contraction  of  the  auricles, 
which  may  last  about  "05  sec.  This  elevation,  which  is  not  always 
present,  is  immediately  followed  by  the  ventricular  contraction,  which 
lasts  from  0  to  2.  From  0  to  1  the  ventricle  is  getting  up  pressure, 
so  that  at  1  the  intraventricular  pressure  is  equal  to  the  aortic  pressure. 
This  process  takes  from  -02  to  -04  sec.  Directly  the  intraven- 
tricular pressure  rises  above  this  point  the  aortic  valves  open  and 
blood  is  driven  into  the  aorta.  The  outflow  of  blood  lasts  from  1  to  2, 
about  0-2  sec.  At  2  the  ventricle  suddenly  relaxes,  the  period  of 
relaxation  occupying  about  "05  sec.  The  flat  part  of  the  curve  is 
often  spoken  of  as  the  systolic  plateau,  and  on  an  average  occupies 
about  -18  sec.  According  to  the  condition  of  the  heart  and  peri- 
pheral resistance,  this  plateau  may  present  a  gi-adual  ascent  or  descent 
V.     Fig.    416).    Almost    immediately     after   relaxation    commences 


KB 

0  1  2  3  0  1  2  3 

FiCi.  39G.     Curve  ol  intraventricular  pressure  V,  compared  with  pressure  in 
aorta  a.     Each  vibration  of  time-marker  =  iJ^sec.     (Hurthle.) 


the  intraventricular  pressure  falls  below  the  aortic,  so  that  the  aortic 
valves  close  somewhere  near  the  upper  part  of  the  descent  (at  3). 

The  ventricular  tracing  can  thus  be  divided  into  the  following 
parts  : 

(1)  A  small  elevation  due  to  the  contraction  of  the  auricles, 
•05  sec. 

(2)  A  very  steep  ascent,  about  the  middle  of  which  the  aortic  valves 
open.  The  point  at  which  these  valves  open,  which  is  about  -02  to 
•04  sec.  after  the  beginning  of  the  rise,  is  not  as  a  rule  marked  on  the 
pressure  tracing. 

(3)  A  prolonged  stage  lasting  about  two-tenths  of  a  second,  during 
which  the  pressure  remains  almost  level,  or  rises  or  falls  slightly,  and 
known  as  the  plateau. 

(4)  A  rapid  fall  due  to  the  relaxation  of  the  ventricular  muscle. 
The  beginning  of  this  fall  is  attended  by  closure  of  the  aortic  valves, 
signalled  in  some  cases  by  a  distinct  notch  in  the  curve. 

(5)  A  very  gradual  ascent,  during  which  the  relaxed  ventricles  are 


1014 


PHYSIOLOGY 


being  gradually  filled  with  blood  flowing  in  from  the  great  veins  and 
arteries. 

The  period  of  outflow  of  blood,  which  lasts  over  the  whole  of  the 
plateau  and  during  the  latter  part  of  the  ascending  portion  of  the 
curve,  represents  the  period  during  which  the  aortic  valves  are  open 
and  the  pressure  in  the  ventricle  is  slightly  higher  than  that  in  the 
artery. 

The  maximum  pressure  in  the  left  ventricle  of  the  dog  may  amount 
to  200  mm.  Hg,  but  is  more  usually  about  130  to  140  mm.  Hg.     On 


Sec. 


i 


yij      1/  S 

Fig.  397.     Curve  of  pressure  in  left  ventricle  of  cat.     (Straub.) 
AS,  auricular  systole  ;   vs,  ventricular  systole. 


the  right  side  the  maximum  pressure  is  probably  much  less — 25 
to  35  mm.  Hg.  The  general  course  of  events  is,  however,  approximately 
identical  on  the  two  sides  of  the  heart. 

Straub  has  lately  investigated  the  course  of  the  pressure  changes  in  the 
auricles  and  ventricles  of  the  cat.  In  order  to  avoid  friction  he  used  the  method 
devised  by  Rolleston  of  plunging  a  cannula  through  the  heart  wall  directly  into 
the  cavity  under  investigation.  Directly  connected  with  this  cannula  was  a 
manometer  consisting  of  a  membrane,  the  movements  of  which  were  recorded 
photographically,  as  in  Frank's  manometer.  A  curve  obtained  in  this  way 
is  shown  in  Fig.  397.  It  is  interesting  that  no  trace  is  to  be  seen  in  these  cm-ves 
of  the  systolic  plateau  or  of  any  secondary  waves,  though  they  are  not  unlike 
the  systolic  part  of  the  aortic  prcssm-e  curve  as  recorded  by  Frank  with  his 
improved  methods.  The  first  heart  sound  is  also  shown  in  the  originals  of  these 
tracings  as  fine  vibrations  just  before  the  systolic  rise.  No  trace  is  seen  of  the 
second  heart  sound,  which  would  fall  on  the  rapidly  descending  part  of  the 
curve. 


THE  MECHANISM  OF  THE  HEART  PUMP 


1015 


CHANGES  OF  PRESSURE  IN  THE  AURICLES 
Owing  to  the  absence  of  valves  between  the  right  auricle  and  the 
venae  cavse,  changes  of  pressure  within  this  cavity  are  transmitted 
along  the  veins.  The  venous  pulsation  is  especially  marked  in  circum- 
stances which  give  rise  to  high  venous  pressure,  so  that  the  veins  are 
not  entirely  emptied  at  any  part  of  the  cardiac  cycle.  The  most  super- 
ficial observation  shows  that  the  jugular  vein  pulsates  twice  for  each 
heart-beat.  The  relation  of  the  alterations  of  pressure  in  the  auricle 
to  those  in  the  ventricle  is  well  shown  in  the  accompanying  diagram 


Fig.  398.  Simultaneous  tracings  of  pressuics  in  aorta  (dotted  line), 
left  ventricle,  and  left  auricle.  The  time  of  occurrence  of  the  heart 
sounds,  and  the  opening  and  closing  of  the  valves  are  also  shown. 

(FRfeoiKICQ.) 


by  Fredericq  (Fig.  398).     The  auricle  curve  presents  the  following 
features  : 

(1)  The  first  positive  wave  (pre-systolic  wave)  corresponding  to 
the  auricular  systole. 

(2)  The  second  positive  wave  66'  or  be  (first  systolic  wave) 
occupying  the  beginning  of  the  ventricular  systole.  This  is  caused  by 
the  sharp  closure  of  the  tricuspid  valve. 

(3)  A  steep  first  negative  wave  b'd,  caused  by  the  opening  of 
the  semilunar  valves  and  the  projection  of  the  blood  from  the  ven- 
tricles into  the  large  arteries.  This  negative  pressure  can  be  regarded 
as  due  partly  to  the  ballistic  recoil  of  the  heart  as  it  shoots  out  a  mass 
of  blood,  partly  to  the  lengthening  of  the  arteries  and  the  corresponding 
movement  of  the  auriculo-ventricular  ring  towards  the  diaphragm. 


1016 


PHYSIOLOGY 


(4)  A  third  positive  wave  (second  systolic  wave)  wliich  may  present 
secondary  undulations.  This  rise  of  pressure  is  due  to  the  gradual 
filling  of  the  auricles  while  the  auriculo -ventricular  valves  are  still 
shut. 

(5)  A  negative  wave  fg  which  corresponds  to  the  '  post-systolic 
vacuum  '  of  Chauveau  and  Marey.  At  /  the  ventricle  is  entirely 
relaxed  and  the  auriculo-ventricular  valves  open,  so  allowing  the 
blood  to  flow  freely  from  the  auricle  into  the  ventricle.* 

For  comparison  with  this  curve  a  tracing  of  the  auricular  pressure 
taken  by  the  more  perfect  method  of  Straub  is  given  (Fig.  399).  It  will 
be  seen  that  in  their  general  features  the  curves  resemble  one  another  ; 
the  more  delicate  manometer  of  Straub  shows,  however,  greater  and 


Fig.  399.     Curve  of  pressures  in  left  auricle  of  cat.     (Straub.) 
I,  II,  III  Ton  =  1st,  2nd,  and  3rd  heart  sounds. 

more  sudden  variations  than  appear  in  Fredericq's  tracing.  Straub 
draws  attention  to  the  fact  that  the  pressure  rises  in  the  left  auricle  to 
a  greater  extent  than  in  the  right  auricle.  In  the  latter  case  the  big 
veins  act  as  a  supplementary  reservoir  to  the  auricle,  so  that  in  no 
period  of  the  cardiac  cycle  need  the  pressure  rise  to  any  extent  in  the 
latter  chamber. 

NEGATIVE  PRESSURE 

It  will  be  noticed  in  the  curve  of  endocardiac  preBsure  (Fig.  396)  that  the 
line  drawn  by  the  lever  descends  slightly  below  the  base  line  at  the  end  of 
systole.  This  is  the  period  at  which  a  negative  pressure  may  occur.  Several 
explanations  have  been  suggested  for  the  production  of  this  negative  pres- 
sure. When  the  flow  of  fluid  through  a  tube  is  suddenly  interrupted, 
the  column  of  fluid,  which  has  a  certain  degree  of  inertia,  tends  to  go  on,  so 
that   a   negative   pressure  is  produced  in  its  rear.    If,  however,  the  negative 

*  It  is  evident  that  Fr6d6ricq's  ciu-ve  of  the  endocardiac  pressme  cannot  be 
quite  correct  at  this  point  ;  since  the  blood  is  flowing  from  auricle  into  ventricle 
the  pre.s.sure  in  the  ventricle  must  be  lower  than  that  in  the  auricle. 


THE  MECHANISM  OF  THE  HEART  PUMP  1017 

pressure  in  the  ventricle  were  due  to  the  sudden  cessation  of  liow  through  the  first 
part  of  the  aorta,  we  ought  to  obtain  with  the  minimvim  manometer  a  negative 
pressure  at  the  root  of  the  aorta  equal  to  that  found  in  the  ventricle.  But  this 
is  not  the  case,  so  that  the  cause  of  the  negative  pressure  must  be  sought  in 
the  ventricle  itself.  It  is  probably  due  to  tlie  fact  that  during  ventricular  contrac- 
tion the  base  of  the  heart,  includuig  the  orifices  of  the  pulmonary  artery  and 
aorta,  is  constricted.  Directly  the  ventricle  relaxes,  the  pressure  of  blood  m  these 
two  triuiks  causes  a  dilatation  of  their  bases  and  therefore  of  the  base  of  the 
heart.  This  dilatation  of  the  base  of  the  heart  increases  its  capacity,  and  so 
creates  a  negative  pressvire  in  the  ventricular  cavities.  This  mode  of  production 
of  the  negative  pressure  may  be  illustrated  experimentally  by  connecting  a 
manometer  with  the  interior  of  either  of  the  ventricles  of  an  excised  heart  that 
has  ceased  beatuig,  and  then  forcing  fluid  into  the  aortic  and  pulmonary  arteries. 
With  each  distension  of  the  arteries  so  produced  the  mercury  in  the  manometer 
siiiks,  showing  the  production  of  a  negative  pressure  in  the  ventricles. 

CHANGES  IN  FORM  OF  THE  HEART 
As  the  heart  walls  are  perfectly  flaccid,  during  diastole,  the  shape 
of  this  organ  as  a  whole  will  depend  upon  the  position  in  which  the 
heart  is  lying  and  the  direction  of  its  support.  Thus  if  the  chest  and 
the  pericardium  be  opened  and  the  animal  be  in  the  supine  position, 
the  heart  during  diastole  will  be  flattened  from  before  backwards  as 
a  result  of  the  simple  weight  of  its  contents.  In  this  position  therefore 
systole  will  be  accompanied  by  a  shortening  in  the  lateral  and  ver- 
tical directions  and  a  lengthening  in  the  sagittal  direction.  During 
systole,  when  the  heart  becomes  tense  and  all  its  fibres  are  firmly 
contracted,  the  heart,  whatever  its  pre\aous  condition,  takes  the  form 
of  a  truncated  cone.  Under  normal  circumstances  the  heart  in  the 
unopened  chest  lies  in  the  pericardium,  which  is  attached  above  to  the 
great  vessels  and  below  to  the  central  tendon  of  the  diaphragm.  It 
is  supported  laterally  by  the  lungs,  which,  however,  owing  to  their 
elasticity,  have  very  little  influence  on  the  diastohc  shape  of  the 
heart. 

When  the  heart  is  freed  from  the  pericardium,  the  obhquity  of  its 
fibres  causes  the  apex  to  move  forwards  and  to  the  right  during  systole  ; 
this  movement  is  normally  prevented  by  the  attachment  of  the  pericar- 
dium to  the  central  tendon  of  the  diaphragm,  so  that  the  most  movable 
part  of  the  heart  comes  to  be  the  base.  If  three  needles  be  passed 
through  the  chest  wall  so  that  their  points  lie,  one  in  the  base,  one  about 
the  centre  of  the  ventricles,  and  one  in  the  apex  of  the  ventricles,  each 
ventricular  systole  is  found  to  be  accompanied  by  a  movement  of  the 
needle  in  the  base  of  the  heart  downwards,  a  slighter  movement  in  the 
same  direction  of  the  needle  in  the  middle  of  the  ventricles,  and  prac- 
tically no  movement  at  all  of  the  needle  which  is  thrust  into  the  apex. 
During  systole  the  base  of  the  heart  moves  downwards  towards 
the  apex.  This  movement  is  determined  partly  by  the  shortening 
of  the  fibres  of  which  the  ventricular  wall  is  composed,  partly  by  the 


1018  PHYSIOLOGY 

lengthening  of  the  great  arteries  as  blood  is  forced  into  them  under 
pressure  from  the  ventricles. 

The  changes  in  the  shape  of  the  cavities  of  the  heart  during  contrac- 
tion have  been  studied  in  the  stage  of  extreme  contraction  produced 
by  heat  rigour.  In  such  hearts  it  is  found  that  the  cavities  are  never 
entirely  obhterated,  though  the  right  ventricle  is  reduced  to  a  narrow 
slit  widening  out  slightly  in  the  neighbourhood  of  the  auriculo-ventri- 
cular  orifices,  while  in  the  left  ventricle  a  distinct  cavity  is  left  between 
the  mitral  valves  and  the  free  ends  of  the  papillary  mu.scles.  During 
normal  activity  it  is  probable  that  the  emptying  of  the  cavities  never 
proceeds  to  so  great  an  extent. 

THE   APEX  BEAT 

The  movement  of  the  heart  at  each  contraction  is  communicated 
to  the  chest  wall,  over  a  limited  area  of  which  it  may  be  felt  and 
seen,  except  in  fat  individuals.  The  region  where  the  pulsation  of  the 
chest  wall  is  most  marked  lies  in  the  fifth  intercostal  space,  a  little 
to  the  median  side  of  the  left  nipple.  The  pulsation  is  spoken  of  as  the 
'  apex  beat,'  and  was  formerly  thought  to  be  due  to  the  twisting  forward 
of  the  apex  at  each  systole.  The  apex  of  the  heart  is  really  situated 
lower  down,  and,  as  we  have  already  seen,  so  long  as  the  pericardium 
is  intact  is  relatively  motionless.  During  diastole  the  ventricles  form 
a  flabby  flattened  cone  lying  against  the  chest  wall  and  slightly  deformed 
by  the  latter.  In  systole  the  ventricles  contract  forcibly  on  the  con- 
tained fluid  and  become  hard  and  rigid,  assuming  the  form  of  a  rounded 
cone.  This  sudden  recovery  of  shape  and  hardening  of  the  ventricular 
walls  pushes  out  the  part  of  the  chest  wall  in  immediate  proximity  to 
the  ventricles  and  so  gives  rise  to  the  '  apex  beat.' 

The  cardiac  impulse  may  be  registered  by  means  of  a  cardiograph. 
In  nearly  all  forms  of  this  instrument  a  button  resting  on  the  chest 
wall  transmits  the  movement  of  the  latter  to  a  tambour,  which  again 
is  connected  by  a  tube  to  a  registering  tambour.  One  such  instrument 
is  shown  in  Fig.  400. 

The  curves  so  obtained,  which  are  known  as  cardiograms,  may 
vary  considerably  in  the  same  subject  according  to  the  pressure 
employed  and  the  exact  spot  at  which  the  tambour  is  applied.  Their 
interpretation  often  presents  difiiculties  owing  to  the  fact  that 
their  form  is  conditioned  by  two  factors,  viz.  (1)  the  actual  size 
(antero-posterior  diameter)  of  the  ventricles,  (2)  the  resistance  to 
distortion  {i.e.  the  tension)  of  the  ventricular  wall ;  this  factor  will 
increase  in  importance  with  increasing  pressure  of  the  cardiograph 
button  on  the  chest  wall.  Fig.  401  represents  a  cardiographic  tracing 
or  cardiogram  which  may  be  spoken  of  as  typical.  In  order  to  interpret 
this  curve  we  must  record  at  the  same  time  either  the  intraventricular 


THE  MECHANISM  OF  THE  HEART  PUMP 


1019 


pressure  in  animals  or  the  heart  sounds  in  man.  This  cardiogram 
presents  considerable  similarities  to  the  endocardiac  pressure  curve  ; 
in  both  there  is  an  ascending  limb,  a  plateau,  and  a  descending 
limb,  and  in   many  cases  a  small  elevation  occurs  at  the   begin- 


FiG.  400.  A  cardiograpli.  This  is  strapped  ruund  the  ehest,  the  central 
button  is  applied  to  the  '  apex  beat,'  and  its  pre.ssure  on  the  chest  wall 
regulated  by  means  of  the  three  screws  at  the  sides.  The  tube  at  the 
upper  part  of  the  instrument  serves  to  connect  the  drum  of  the  cardio- 
graph with  a  registering  tambour  such  as  that  shown  in  Fig.  391. 

ning  of  a  curve  during  the  contraction  of  the  auricle.  The  exact 
point  at  which  the  auricular  passes  into  the  ventricular  contraction 
varies  from  case  to  case  and  may  be  altered  by  altering  the  degree  of 
pressure  put  on  the  recording  button.  In  the  first  figure  given  the 
auricular  systole  finishes  before  the  main  rise  of  the  lever  occars.  In 
many  cases,  however,  the  elevation  due  to  the  auricular  systole  may 
take  up  the  greater  part  of  the  ascending  limb  of  the  curve,  as  in 
Fig.  402. 

In  the  experiment  from  which  this  figure  was  taken  the  heart 


Fia.  401.     Cardiogram.     (Hubthle.) 

sounds  were  recorded  at  the  same  time  as  the  apex  beat.  It  will  be 
seen  that  the  first  heart,  sound,  corresponding  to  the  ventricular  systole, 
begins,  not  at  the  commencement  of  the  rise  of  the  cardiogram,  but 
at  the  notch  near  the  top  of  the  ascent.  The  first  part  of  the  ascent 
is  therefore  caused  by  the  increase  in  the  volume  of  the  ventricle,  due 
to  the  sudden  contraction  of  the  auricles,  the  ventricular  systole  being 
marked  by  the  notch  near  the  top  of  the  curve.  Owing  to  the  co-opera- 


1020 


PHYSIOLOGY 


tion  of  the  volume  and  pressure  factors  in  the  production  of  the  cardio- 
gram, the  curve  generally  begins  to  decline  with  the  diminution  in 
volume  which  follows  the  sudden  opening  of  the  aortic  valves.  Here 
again,  however,  the  effect  will  vary  with  the  pressure  of  the  button.  If 
an  actual  deformation  of  the  ventricular  muscle  can  be  effected,  as  in 


1  2 

Fig.  402.     Cardiogram  (b)  with  simultaneous  record  of  heart-sounds  (a). 

(HURTHLE.) 

1,  position  of  first  heart-sound  ;   2,  position  of  second  heart-sound, 

thin  patients,  the  plateau  of  the  curve  may  last  during  the  whole  of  the 
cardiac  cycle.  Other  forms  of  curves  may  be  obtained  which  show 
considerable  deviation  from  the  endocardiac  pressure  tracing  ;  these 
are  spoken  of  as  atypical,  and  are  generally  conditioned  by  a  faulty 
position  of  the  cardiograph,  the  button  being  applied  to  the  chest  wall 
in  the  immediate  vicinity  of  the  apex  beat  instead  of  to  the  apex  beat 
itself. 
V.  THE  HEART  SOUNDS 

If  we  apply  our  ear  to  the  front  of  a  person's  chest  (it  is  more 
convenient  to  use  the  stethoscope  for  the  purpose)  we  hear  two  dis- 
tinct sounds  accompanying  each  beat  of  the  heart,  followed  by  a 
pause  corresponding  to  the  diastole.  The  sounds  are  compared  to  the 
syllables  lubb,  dup,  the  first  sound  being  low-pitched  and  prolonged, 
the  second  sound  high  and  sharp.  Thus  the  heart  sounds  may  be 
represented  :    lubb,  dup  (pause),  lubb,  dup  (pause). 

The  causation  of  the  second  sound  is  very  simple,  and  may  be 
considered  first.  It  is  heard  just  over  the  second  right  costal  cartilage, 
i.e.  the  place  where  the  aorta  lies  nearest  the  surface.^  It  comes  at  the 
end  of  the  systole,  as  determined  by  the  hardening  of  the  apex  of  the 
heart,  felt  as  the  apex  beat,  and  can  be  shown  to  be  synchronous 
with  the  closure  of  the  aortic  valves.  It  is,  in  fact,  caused  by  the  sudden 
shutting  and  stretching  of  these  valves  that  occur  directly  the  heart 
ceases  to  contract  and  to  force  the  blood  into  the  aorta.  If  the  valves 
be  hooked  back  in  an  animal  by  means  of  a  wire  passed  down  a  carotid 
artery,  the  second  sound  disappears  and  is  replaced  by  a  murmur 
caused  by  the  blood  rushing  back  into  the  ventricle  at  the  end  of  the 


THE  MECHANISM  OF  THE  HEART  PUMP    1021 

systole.  The  same  disappearance  of  the  normal  second  sound  is 
observed  in  cases  where  the  valves  are  prevented  from  closing  by 
diseased  conditions. 

The  pulmonary  and  aortic  valves  generally  close  simultaneously. 
In  some  cases,  however,  the  aortic  may  close  slightly  before  the 
pulmonary,  giving  rise  to  a  '  reduplicated  second  soimd.'  The 
pulmonary  element  of  this  sound  is  best  heard  over  the  second  left 
cartilage,  or  in  the  second  left  intercostal  space. 

The  first  sound  has  probably  a  twofold  origin,  viz.  from  the  sudden 
closure  of  the  auriculo-ventricular  valves  and  from  the  contraction  of 
the  thick  muscular  wall  of  the  ventricle. 

If  the  veins  going  to  the  heart  be  clamped  so  that  the  heart  can 
no  longer  be  distended  with  blood  nor  the  valves  put  on  the  stretch, 
the  second  sound  is  altered  in  character,  but  not  abolished.  The  first 
sound  may  indeed  be  heard  on  Listening  with  a  stethoscope  to  the  beat 
of  an  excised  heart.  It  is  said  that  two  notes  may  be  detected  in  the 
first  sound — a  high  note  of  short  duration  due  to  closure  of  the  valves, 
and  a  low-pitched  note  due  to  the  muscular  contraction.  The  muscular 
element  of  the  first  sound  has  the  same  pitch  as  the  sound  produced 
by  contracting  voluntary  muscle,  and  therefore  as  the  resonance-tone 
of  the  ear.  This  consideration  prevents  our  arguing  from  the  tone  that 
a  cardiac  contraction  is  a  tetanus.  As  we  shall  show  later  on,  each 
ventricular  contraction  is  analogous  to  a  simple  muscle-twitch  and  not 
to  a  tetanus. 

THE  THIRD  HEART  SOUND,  Anumberof  observers  have  described  a  third 
heart  sound  as  occuiring  in  certain  individuals  during  the  diastole,  a  short  time 
after  the  second  sound.  It  is  softer  and  of  a  lower  pitch  than  the  second  sound, 
and  is  heard  most  distinctly  over  the  apex  beat.  It  is  probably  due  to  the  vibra- 
tions set  up  in  the  fluid  itself  or  in  the  auriculo-ventricular  valves  by  the  sudden 
inrush  of  blood  from  auricles  to  ventricles  at  the  beginning  of  diastole.  The  sound 
is  shown  objectively  by  the  vibrations  on  the  endocardiac  pressvu-e  curve  given 
in  Fig.  .399  (Straub).    It  has  also  been  registered  electrically  by  Einthoven, 

CARDIAC  MURMURS 

When  a  fluid  escapes  through  a  narrow  orifice  into  a  wider  space 
vibrations  are  set  up  in  the  fluid  and  may  be  transmitted  by  any 
elastic  medium  to  the  ear,  giving  rise  to  the  sensation  of  sound.  Such 
a  sound  is  produced  when  water  is  allowed  to  run  from  a  tap  into  a 
vessel  of  water,  or  when  air  is  blown  out  between  the  partially  closed 
lips.  The  formation  of  such  vibrations  forms,  indeed,  the  basis  for  the 
construction  of  many  musical  instruments.  The  same  sort  of  vibration 
may  be  set  up  in  the  large  vessels  or  in  the  heart,  whenever  the  blood 
passes  rapidly  through  a  narrow  orifice  into  a  wider  space. 

In  the  normal  individual  sounds  produced  in  this  way  are  so  slight 
that  they  may  be  neglected  ;    under  abnormal  conditions,  as  after 


1022  PHYSIOLOGY 

diseases  affecting  the  valvular  orifices  of  the  heart,  this  vibration  may 
occur  during  every  heart  cycle  and  be  heard  with  ease  on  applying 
the  ear  to  the  chest.  These  murmurs,  or  bruits  as  they  are  called, 
are  of  paramount  importance  in  enabling  the  medical  man  to  form 
a  judgment  as  to  the  condition  of  the  different  valves  of  the  heart. 
Thus  injury  to  an  aortic  valve,  so  as  to  allow  of  leakage  during  diastole, 
involves  the  squirting  of  a  small  amount  of  fluid  under  high  pressure 
from  the  aorta  into  the  relaxed  ventricle.  On  listening  to  the  chest  of  a 
man  with  such  a  lesion  this  regurgitation  during  diastole  is  heard  as  a 
rushing  sound  occurring  in  the  place  of  or  continuing  the  second 
sound  up  to  the  beginning  of  the  next  first  sound  which  denotes  the 
beginning  of  systole. 

In  many  cases  the  disease  which  occasioned  the  inadequacy  of  the 
valve  is  followed  by  processes  of  repair  and  cicatrisation  in  which  the 
valves  become  puckered  and  contracted  and  perhaps  adherent,  so 
that  the  orifices  can  never  become  thoroughly  patent  or  thoroughly 
closed.  Under  such  circumstances  vibrations  wiU  be  set  up  in  the 
current  of  blood  as  it  escapes  through  the  narrow  orifice  into  the 
aorta  during  systole,  and  on  listening  to  the  chest  over  the  second 
right  costal  cartilage  a  '  to  and  fro  '  bruit  is  heard  composed  of  a 
systolic  immediately  followed  by  a  diastolic  murmur.  In  the  same 
way  incompetency  of  the  mitral  valve  or  of  the  mitral  orifices,  in 
consequence  of  weakness  of  the  cardiac  muscle,  gives  rise  to  a  murmur 
which  lasts  during  the  whole  of  the  ventricular  contraction  and  is 
therefore  systolic  in  character.  Such  a  murmur  is  heard  best  over  the 
apex  beat,  and  is  also  transmitted  backwards  so  that  it  can  be  heard 
on  listening  at  the  back  of  the  patient.  A  narrowing  of  the  mitral 
orifice  in  consequence  of  contraction  of  the  valves  will  set  up  a  resist- 
ance to  the  flow  of  blood  from  left  auricle  to  left  ventricle.  The  auricle 
becomes  hypertrophied,  its  contraction  prolonged,  and  the  escape  of 
blood  through  the  contracted  orifices  gives  rise  to  a  murmur  which  is 
heard  on  hstening  over  the  apex  beat  as  a  presystolic  bruit.  This 
bruit  is  easily  distinguished  from  a  systohc  murmur  by  noticing  that 
it  runs  up  to  and  ends  with  the  apex  beat,  whereas  a  systolic  murmur 
does  not  begin  until  the  elevation  of  the  apex  commences. 

Several  play.siologists  have  succeeded  in  recording  heart  sounds  graphically. 
Hiirthle's  method  consists  in  an  apphcation  of  the  microphone.  A  special  form 
of  stetho.scope  is  so  arranged  that  by  its  means  the  vibrations  corresponding  to 
the  heart  sounds  are  transmitted  to  a  contact  between  silver  and  carbon.  Through 
this  contact  a  strong  current  is  passing.  Tliis  also  passes  through  an  electro- 
magnet, which  attracts  an  iron  disc  attached  to  the  membrane  of  a  Marey's 
tambour.  Any  vibration  transmitted  to  the  carbon-silver  contact  alters  its 
resistance,  and  so  the  strength  of  the  current  passing  through  the  electro-magnet. 
In  this  way  the  heart  sounds  can  affect  the  pull  exerted  by  the  electro -magnet 
on  the  membrane  of  the  tambour,  and  the  change  in  the  volume  of  the  contained 
air  is  recorded  by  means  of  an  ordinary  registering  tambour. 


THE  MECHANISM  OF  THE  HEART  PUMP 


1023 


Similar  results  have  been  obtained  by  Einthoven.  who  has  allowed  the 
variations  in  the  current  passing  through  the  microphone  t^j  be  recorded  directly 
by  means  of  a  very  delicate  capillary  or  string  electrometer. 

TIME-RELATIONS 
The  time-relations  of  the  various  events  of  the  cardiac  cycle  are 
indicated  in  the  accompanying  diagram  (Fig.  403).  In  man  the  heart 
beats  on  the  average  about  seventy- two  times  in  the  minute,  so  that 
each  cardiac  cycle — i.e.  systole  j>lus  diastole —  can  be  regarded  as  occu- 
pying 0*8  sec.  During  five-tenths  of  a  second  the  ventricles  are  relaxed  ; 
during  the  first  four-tenths  of  this  period,  which  corresponds  to  the 
diastole  of  the  heart  as  a  whole,  blood  is  flowing  in  a  steady  stream 


Diastole. 


Blood     lowint 
in: ,0  auricles  and 


from 


Mftok 

of 
Aur- 
icles 


S-\  stole 


of 


Ventric'es 


Diastole. 


01        02       03       Oi       00       0  0        07       0^       O'J       10  sees. 

||||||{||{||l||||l||||{||||||!!|i|||{l|^   i  Ineart  Sounds 


.  dup  Luljb dup 

Fig.  403.     Diagram  of  events  constituting  a  cardiac  cycle. 


from  the  veins  through  the  auricles  into  the  ventricles,  so  that  the 
heart  is  gradually  increasing  in  size.  The  systole  of  the  auricle  then 
occurs  and  lasts  about  O'l  sec.  This  is  followed  by  the  ventri- 
cular systole,  the  immediate  effect  of  which  is  to  close  the  auriculo- 
ventricular  valves  on  both  sides  of  the  heart.  The  point  of  closure 
of  the  valves  cannot  be  fixed  with  certainty,  but,  as  has  already 
been  shown,  must  occur  within  an  instant  of  the  time  of  the  commence- 
ment of  the  ventricular  systole.  The  whole  ventricular  contraction 
lasts  03  sec.  ;  during  the  first  period  of  this  the  ventricle  is  getting 
up  pressure,  the  pressure  rapidly  rising  until  it  equals  the  aortic 
pressure.  This  period,  during  which  the  ventricle  is  simply  contracting 
on  its  contents  without  any  flow  of  blood  occurring,  lasts  between  "02 
and  '04  sec,  and  is,  of  course,  longer  the  higher  the  pressure  in 
the  aorta.  Directly  the  intraventricular  pressure  rises  above  this 
point  the  aortic  valves  open  and  blood  is  driven  into  the  aorta.  The 
outflow  of  blood  continues  throughout  the  whole  of  the  ventricular 
systole,  and  may  be  taken  as  lasting  about  0*2  sec.     The  ventricle 


1024  PHYSIOLOGY 

then  saddenly  relaxes,  the  period  of  relaxation  occupying  about 
0"5  sec.  ;  the  plateau  of  the  endocardiac  pressure  curve  on  the  average 
lasts  about  0"18  sec,  and  according  to  the  condition  of  the  heart 
and  the  peripheral  resistance  may  present  a  gradual  ascent  or  descent. 
Directly  relaxation  commences  the  ventricular  pressure  falls  below 
the  aortic  pressure  or  the  pulmonary  pressure  and  the  semilunar 
valves  close,  giving  rise  to  the  second  somid.  Systole  is  now  at  an  end 
and  the  diastolic  period  of  filhng  recommences.  The  first  sound  is 
synchronous  with  commencement  of  the  ventricular  contraction, 
and  the  same  event  is  signalled  by  the  occarrence  of  the  apex  beat. 

Although  the  pulse  frequency  may  undergo  considerable  variations 
according  to  the  condition  of  the  individual,  being  higher  during 
activity  or  under  conditions  of  mental  excitement,  the  greater  part 
of  the  difference  in  duration  of  the  cardiac  cycle  thereby  induced  falls 
upon  the  diastolic  period.  Thus  to  take  wide  limits  the  pulse- rate  may 
vary  between  32  and  124  beats  in  the  minute,  while  under  the  same 
circumstances  the  period  occupied  by  the  systole  only  varies  between 
0'382  and  0*190  sec. — and  these,  of  course,  are  extreme  limits. 
Variation  therefore  in  the  time  occupied  by  each  cardiac  cycle  is 
determined  mainly  by  variation  in  the  time  occupied  by  the  diastole. 

FILLING  OF  THE  HEART  IN  DIASTOLE 
Since  the  heart  is  perfectly  flaccid  during  diastole  it  is  unable  to 
exert  any  suction  force  on  the  blood  in  the  veins.  Its  filling  during 
diastole  depends  on  the  existence  of  a  positive  pressure  within  the 
veins,  or  at  any  rate  of  a  pressure  greater  than  that  in  the  auricles  ; 
the  greater  the  pressure  within  the  large  veins  the  more  rapidly  will 
the  blood  enter  the  heart  during  diastole  and  the  larger  the  amount 
of  blood  in  this  viscus  when  it  begins  its  contraction.  In  this  procees 
an  important  part  is  played  by  the  mechanical  conditions  existing  in 
the  thoracic  cavity.  Owing  to  the  elasticity  of  the  lungs  and  the  fact 
that  they  are  constantly  tending  to  contract,  the  pressure  in  the 
thorax  is  less  than  that  of  the  external  atmosphere  by  the  amount 
which  is  required  to  distend  the  lungs  to  fill  the  cavity. 

At  the  end  of  expiration  this  difference  amounts  to  about  5  mm.  Hg, 
rising  to  9  mm.  Hg  at  the  end  of  inspiration  and  to  30  mm.  Hg  at 
the  end  of  a  forced  inspiration.  On  the  other  hand,  the  veins  outside  the 
thorax  are  exposed  to  a  pressure  which  is  a  little  above  that  of  the 
atmosphere.  When  the  thorax  is  at  rest  the  veins  and  auricles  are 
therefore  expanded  and  the  flow  of  blood  into  them  rendered  more 
easy.  The  respiratory  movements,  by  causing  an  alternating  suction 
on  the  walls  of  the  great  veins,  act  like  an  accessory  pump  and  cause 
an  aspiration  of  blood  into  the  veins  of  the  thorax  with  each  inspiration. 
It  is  evident  that  if  the  pressure  within  the  thorax  be^ufiiciently 


THE  MECHANISM  OF  THE  HEART  PUMP  1025 

raised  so  as  to  cause  a  positive  pressure  on  the  big  veins  and  auricles, 
the  return  flow  of  blood  to  the  heart  must  come  to  an  end.  Tlius 
during  extreme  muscular  efiorts  the  glottis  is  fixed  and  a  positive 
pressure  is  produced  in  the  thorax.  The  deficient  circulalioji  and  the 
deficient  aeration  of  the  blood  thereby  induced  are  shown  by  the 
engorgement  of  the  superficial  veins  and  the  blueness  of  the  surface. 
Weber  showed  that  by  a  forcible  expiration,  with  the  glottis  closed, 
the  pulse  might  disappear  at  the  wrist  and  the  circulation  be  brought 
for  a  time  to  a  standstill,  so  that  even  loss  of  consciousness  might 
supervene. 

Since  the  heart  during  its  systole  diminishes  its  own  volume  by 
the  expulsion  of  blood  from  the  thorax,  it  becomes  smaller,  and  the 
space  thus  provided  in  the  chest  cavity  is  taken  up  by  an  expansion 
of  the  veins,  auricles,  and  lungs.  To  this  systolic  diminution  of  intra- 
thoracic pressure  is  due  the  '  cardio-pneumatic  '  movements.  These 
are  recorded  by  attaching  one  nostril  to  a  deUcate  tambour  by  means 
of  a  tube,  while  the  other  nostril  and  the  mouth  are  kept  closed.  If  a 
carotid  pulse  tracing  be  taken  at  the  same  time  it  will  be  found  that 
there  is  a  fall  of  the  lever  attached  to  the  nasal  cavity  synchronous 
with  the  rise  of  the  pressure  in  the  arteries,  due  to  the  expulsion  of 
blood  from  the  heart. 

The  normal  filHng  of  the  heart  during  diastole  can  be  prevented 
by  anything  which  hinders  its  expansion,  such  as  the  presence  of 
fluid  in  the  pericardial  cavity.  The  same  effect  may  be  produced 
experimentally.  If  oil  be  allowed  to  flow  into  the  pericardium  under 
pressure,  when  the  pressure  of  the  oil  rises  to  about  60  mm.  the 
pressure  of  the  vena  cava  rises  to  a  height  just  above  that  obtaim'ng 
in  the  pericardial  cavity.  On  increasing  the  pressure,  a  point  is  finally 
reached  at  which  no  more  blood  can  be  driven  from  the  veins  to  the 
lieart,  so  that  the  arterial  blood-pressure  falls  to  zero  and  death  ensues. 

In  order  to  maintain  the  arterial  pressure  it  is  necessary  that  the 
amount  of  blood  driven  into  the  arterial  system  by  the  contraction 
of  the  left  ventricle  should  be  exactly  equal  to  that  leaving  the  arteries 
to  pass  into  the  capillaries  during  the  period  which  elapses  between 
each  systole. 

Over- tilling  of  the  heart  is  prevented  to  a  certain  extent  by  the 
resistance  of  its  wails.  The  danger  of  over-filling  is  therefore  most 
marked  in  the  right  ventricle.  An  important  part  is  played  moreover 
by  the  pericardium  in  this  regard.  Even  when  beating  normally,  the 
heart  during  diastole  tends  to  protrude  through  a  slit  made  in  the 
pericardium,  and  Barnard  has  shown  that  the  riglit  auriculo-ventri- 
cular  valve  ceases  to  be  entirely  efficient  when  the  pericardium  has 
been  freely  opened,  the  closure  of  this  valve  being  ilependeiit  on 
the  support  afiorded  to  the  heart  by  the  pericardium. 

66 


1026 


PHYSIOLOGY 


SYSTOLIC  OUTPUT  OF  THE  HEART 
Since  tlie  height  of  the  arterial  pressure  depends  on  tlie  relation 
between  the  amount  of  blood  leaving  the  arterial  system  by  the 
capillaries  and  that  entering  from  the  heart,  the  determination  of  the 
heart  output  becomes  of  considerable  importance.  Several  methods 
have  been  used  for  this  purpose. 

Stolnikow  and  Pawlow  practically  cut  out  the  systemic  circulation 
altogether  and  caused  the  blood  from  the  left  ventricle  to  traverse 


Pig.  40'i.     Diai^ram  of  ytoliiikow's  instiiiuient. 


an  instrument  (current  measurer,  Stromaiche)  which    recorded  auto- 
matically the  amount  of  blood  that  went  through  it  in  a  given  time. 

In  Fig.  iOJ:  I  and  II  are  two  cylinders  containing  accurately 
fitting  floats,  bearing  writing  levers  on  their  upper  ends.  Each  of  these 
communicates  below  with  two  tubes,  a  and  v,  one  of  which  is  con- 
nected to  the  right  carotid  artery,  while  the  other  is  inserted  into  the 
superior  vena  cava.  All  other  branches  of  the  aorta,  as  well  as  the 
inferior  vena  cava,  are  ligatured.  At  the  beginning  of  the  experiment 
cylinder  II  is  filled  with  defibrinated  blood.  This  blood  passes  down 
the  tube  2v  into  the  right  auricle,  and  so  through  the  right  ventricle 
and  lungs,  where  it  is  aerated,  into  the  left  auricle  and  ventricle.  As 
the  heart  continues  beating,  the  left  ventricle  expels  its  contents  into 
cylinder  I,  so  that  the  piston  in  I  is  rising  while  that  in  II  is  falhng. 
As  soon  as  cylinder  II  becomes  cmpl}-  the  tubes  Iv  and  2a  are  released 
and  the  tubes  la  and  2v  are  clamped.    The  left  ventricle  now  expels 


THE  MECHANISM  OF  THE  HEART  PUMP     1027 

its  blood  through,  2a  into  cylinder  II  while  cylinder  I  is  emptying 
isself  through  iv  into  the  right  auricle.  We  thus  get  two  series  of  zig- 
zag lines  traced  by  the  piston  rods,  and  the  frequency  of  the  zigzags  is 
an  expression  of  the  output  of  the  left  ventricle  in  a  given  time. 

This  method  suffers  from  the  defect  that  the  arterial  pressure,  in 
consequence  of  the  absence  of  external  resistance,  is  extremely  low, 
so  that  the  heart  is  throughout  under  highly  abnormal  conditions.  It 
enjoys,  however,  the  corresponding  advantage  that  r  (the  resistance), 
though  low,  is  constant  throughout  the  experiment,  and  the  work 
done  by  the  heart  is  therefore  directly  proportional  to  the  output. 

In  a  method  devised  by  the  author  it  is  possible  to  determine  the 
outjjut  of  the  left  ventricle  under  more  normal  conditions,  and  to 
vary  at  will  the  arterial  resistance,  the  venous  pressure,  the  filling  of 
the  heart,  or  the  temperature  of  the  blood-supply  to  the  heart.  The 
arrangement  of  the  apparatus  is  shown  in  Fig.  405.  Artificial  respi- 
ration being  maintained,  the  chest  is  opened  under  an  anaesthetic. 
The  arteries  coming  from  the  arch  of  the  aorta — in  the  cat,  the  inno- 
minate and  the  left  subclavian — are  then  hgatured,  thus  cutting  off 
the  whole  blood-supply  to  the  brain,  so  that  the  anaesthetic  can  be 
discontinued.  Cannulse  are  placed  in  the  innominate  artery  and  the 
superior  vena  cava.  The  cannulee  are  filled  beforehand  with  a  solution 
of  hirudin  in  normal  salt  solution  so  as  to  prevent  clotting  of  the 
blood  during  the  experiment.  The  descending  aorta  is  closed  by  a  liga- 
ture. The  only  path  for  the  blood  left  is  by  the  ascending  aorta  and 
the  cannula  Ca  in  the  innominate  artery.  The  arterial  cannula 
communicates  by  a  T-tube  with  a  mercurial  manometer  M^  to  record 
the  mean  arterial  pressure,  and  passes  to  another  T-tube,  v,  one  limb 
of  which  projects  into  a  test-tube  B.  The  air  in  this  test-tube  will  be 
compressed  with  a  rise  of  pressure  and  will  serve  as  a  driving  force 
for  the  blood  through  the  resistance.  It  thus  takes  the  part  of  the 
resilient  arterial  wall.  The  other  limb  of  the  T-tubo  passes  to  tlie 
resistance  R.  This  consists  of  a  tliin-wallcd  rubber  tube  {e.g.  a  rubber 
finger-stall)  which  passes  through  a  wide  glass  tube  provided  wit-h 
two  lateral  tul)ulures  w,  w.  One  of  these  is  connected  witli  a  mercurial 
uumometer  M'  and  the  other  with  an  air  reservoir  A,  into  which  air  can 
be  pumped  by  the  elastic  bellows  S.  When  air  is  injected  into  the  outer 
tube  the  tube  R  collapses,  and  will  remain  collapsed  until  the  pressure 
of  the  blood  within  it  is  equal  or  superior  to  the  pressure  in  the  air  sur- 
rounding it.  It  is  thus  possible  to  vary  at  will  the  resistance  to  the 
outflow  of  the  blood  from  the  arterial  side.  From  the  peripheral  end  of 
R  the  blood  passes  at  a  low  pressure  and  is  collected  in  a  vessel  N,  which 
is  provided  with  a  siphon,  and  can  be  made  of  such  dimensions  that  the 
blood  is  si[)honed  oil"  as  soon  as  10,  20,  or  30  c.e.  have  collected  in  the 
vessel.     .V  lateral  branch  o»i  the   siphon    tube  leads  by  a  rubber  tube 


1028 


PHYSIOLOGY 


to  a  tambour  D.  Every  time  that  siphonage  occurs  there  is  a  change 
of  pressure  within  the  tambour,  which  can  be  registered  by  the  lever 
on  a  blackened  surface.  The  siphon  discharges  the  blood  into  a  reser- 
voir F,  which  is  kept  immersed  in  a  vessel  of  water  maintained  at 
any  desired  temperature   by  some  source   of  heat.    From  the  spiral 


Fia.  405.     Aiiau;^(.iiicnt  of  appaiatii.s  lor  workiiij:;  on  the  isolated 
manimaliau  heart.     (Knowlton  and  Stakling.) 

below  F,  an  india-rubber  tube  leads  to  a  cannula  CV ,  which  is  placed 
in  the  superior  vena  cava,  all  the  branches  of  which  have  been  tied. 
This  cannula  is  provided  with  a  thermometer  to  sliow  the  temperature 
of  the  blood  supplied  to  the  heart.  A  tube  placed  in  tlie  inferior  vena 
cava  and  connected  with  a  Avater  manometer  shows  the  pressure  in 
the  right  auricle.  On  the  recording  surface  we  thus  have  a  record  of 
the  aHerial  prcssui'c,  of  the  output  of  the  wliole  system,  as  reccjrdcd 
by  the  tambour,  and  of  the  pressure  within  tlie  right  auricle,  if  desired 


THE  MECHANISM  OF  THE  HEART  PIMP 


1029 


the  simple  current  measurer  described  on  p.  I0(j|  ran  be  inserted  in  the 
arterial  circuit  at  X,  so  as  to  fjivo  immediately  the  output  of  the  left 
ventricle. 

Other  methods  are  based  upon  tlie  application  of  the  plethysmo- 
graphic  method  to  the  heart  in  situ.  We  may  either,  as  in  Tigerstedt's 
method,  employ  the  pericardium  itself  filled  with  oil  or  air  as  the 
oncometer,  and  register  the  changes  in  the  volume  of  the  heart  by 
connecting  the  cavity  of  the  pericardium  with  some  form  of  piston 


Fig.  406.     Diagram  of  Roy's  cardiometer. 
On  the  right  of  the  figure  are  the  two  quarter-spheres  which  are  elamped 
on  to  the  pericardium  at  the  root  of  tlie  heart. 


recorder,  or  we  may  make  use  of  Roy's  cardiometer.  This  is  a  brass 
sphere  in  three  segments.  The  two  quarter-spheres  (Fig.  406)  are 
applied  round  the  base  of  the  heart  and  clamped  together,  the  cut 
pericardium  being  attached  to  their  constricted  neck.  The  rMrd 
segment,  a  hemisphere,  is  then  applied  over  the  apex  of  the  ventricles 
and  clamped  to  the  parts  already  in  situ.  Attached  to  the  centre  of 
this  hemisphere  is  a  modified  piston-recorder  containing  a  piston 
working  in  oil,  with  which  the  whole  of  the  apparatus  is  filled.  At  a 
is  a  spring  which  can  be  adjusted  so  as  to  exercise  a  constant  pull 
upon  the  piston  and  reproduce  to'some  extent  the  nefjative  pressure 
under  which  the  heart  normally  works.   The  piston-rod  carries  a  lever 


1030  PHYSIOI>OGY 

which  writes  on  a  blackened  surface.  The  excursions  of  this  lever  are 
proportional  to  the  diminution  in  volume  of  the  heart  at  each  systole 
and  therefore  serve  as  a  measure  of  the  output  of  the  ventricles.  Instead 
of  this  brass  sphere  a  glass  cardiometer  may  be  used  (Henderson) 
consisting  of  a  glass  sphere  with  a  wide  opening,  with  a  rubber  dia- 
phragm which  is  slipped  on  the  heart  until  the  edge  of  the  diaphragm 
rests  in  the  auriculo- ventricular  groove  (Fig.  407). 

An  attempt  lias  been  made  to  determine  the  output  of  the  ventricles  from 
the  time  taken  up  in  the  total  circulation.  A  solution  of  methylene  blue  injected 
into  the  central  end  of  the  jugular  vein  can  be  detected  in  the  blood  flowing 
from  the  peripheral  end  of  the  same  jugidar  after  twenty-seven  heart-beats. 
This  has  been  interpreted  erroneously  as  equivalent  to  saying  that  the  whole 


/ 

Fig.  407.     Henderson's  glass  cardiometer. 


blood  made  the  whole  circuit  of  the  vascular  system  and  therefore  passed  through 
the  heart  twice  in  twenty-seven  heart-beats.  Thus  we  should  have  only  to  divide 
the  quantity  of  blood  in  man  (.3000  grm.  in  a  man  of  60  Idlos)  by  27  in  order 
to  arrive  at  the  output  of  each  ventricle  at  each  cardiac  systole,  i.e.  about  111  grm. 
It  is  evident,  however,  that  the  figure  obtained  by  the  methylene -blue  method 
merely  represents  the  shortest  possible  time  in  which  any  given  particle  of  blood, 
taking  all  the  short  cuts  which  may  be  open,  can  travel  round  the  whole  circula- 
tion, so  that  the  true  output  of  the  left  ventricle  in  man  must  be  cf)nsiderably 
less  than  111  grm.  and  is  probably  not  more  than  one-half  of  this  amount. 

Zuntz  has  emploj'ed  an  indirect  metlK)d  of  determining  the  output  of  eaich 
ventricle  based  on  a  comparison  of  the  differences  in  gases  contained  between 
arterial  and  venous  blood  and  the  actual  amount  of  oxygen  taken  from  the  air 
in  the  lungs.  Thus  in  one  case  he  found  that  in  a  horse  weighing  300  kikis  2733  c.c. 
of  <^'gen  were  taken  up  in  the  lungs  per  minut«,  while  the  arterial  blood  contained 
lO'SS  per  cent,  more  oxygen  than  the  venous  blood.  Since  therefore  every 
100  c.c.  of  blood  that  passed  through  the  lungs  had  taken  up  10*33  c.c.  of  oxygen, 
and  2733  c.c.  had  been  taken  up  in  the  course  of  a  minute,  it  is  evident  that 


100    X   2733 
10-33 


=  26,457  c.c. 


of  blood  must  have  passed  through  the  lungs  in  the  time.    This  therefore  was 
the  output  of  blood  by  the  right  ventricle  in  n  minute  and  Avas  eqin'vakiit  to 
00122  of  tlie  body-weight  per  second. 


THE  MECHANISM  OF  THE  HEART  PUMP     1()3I 

In  a  similar  oxperimcnt  on  a  dog  the  output  per  second  of  the  right  ventricle 
was  found  to  be  -00157  of  the  body-weight.  In  order  to  get  the  output  at  each 
beat  it  will  be  neccssarj'  to  divide  the  output  per  minute  by  the  number  of 
heart-beats  in  the  same  time. 

From  the  results  of  these  various  determinations  on  animals  it 
has  been  calcuhted  that  the  output  of  the  right  ventricle  in  man  at 
each  beat  is  equivalent  to  between  50  and  100  c.c.  and  may  be  taken 
on  an  average  at  60  c.c.  The  output  of  the  left  ventricle  must  be 
exactly  equal  to  that  of  the  right  ventricle,  otherwise  there  would 
be  a  damming  up  of  the  blood  at  some  part  or  other  of  the  circulation. 
The  output  depends  chiefly  on  the  diastolic  filling  of  the  heart.  It  is 
therefore  increased  by  any  factor  which  increases  the  latter,  such  as 
rise  of  venous  pressure  or  lengthened  diastole,  such  as  occurs  during 
enforced  slowing  of  the  heart-beat. 

THE  WORK  OF  THE  HEART 

The  energy  of  the  ventricular  contraction  is  expended  in  two  ways  : 
firstly,  in  forcing  a  certain  amount  of  blood  into  the  alreadv  dis- 
tended aorta  against  the  resistance  presented  by  the  arterial  blood- 
pressure,  which  itself  is  directly  conditioned  by  the  re'sistance  in 
arterioles  and  capillaries  ;  and  secondly,  in  imparting  a  certain  velocity 
to  the  mass  of  blood  so  thrown  out.  Thus  the  energy  of  the  muscular 
contraction  is  converted  partly  into  potential  energy  in  the  form  of 
increased  distension  of  the  arterial  wall,  and  partly  into  the  kinetic 
energy  represented  by  the  momentum  of  the  moving  column  of  blood. 
The  work  done  at  each  beat  may  be  calculated  from  the  formula  : 

W  =  QR  +  — - 

where  W  stands  for  work,  ^v  for  the  weight,  and  Q  for  the  quantity 

(volume    in    c.c.)  of  blood  expelled  at  each  contraction  :    R    is  the 

average  arterial  resistance  or  pressure  during  the  outflow  of  blood  from 

the  heart,  and  V  is  the  velocity  of  the  blood  at  the  root  of  the  aorta. 

In  this  equation  QR  is  the  work  done  in  overcoming  the  resistance,* 

wY'^  . 
and  — —  is  the  energy  expended  in  imparting  a  certain  velocity  to  the 
2f/  ' 

blood. 

If  we  take  OO  c.c.  as  the  average  output  of  each  ventricle,  1(H)  mm. 

*  Tliis  expression,  QR,  is  only  apijroxiinatcl^-  correct.  Supposing  the  pressure 
in  the  aorta  at  the  l)eginning  of  systole  is  50  nun.  Kg.  and  at  the  end  of  .'^ystole 
150  mm.,  the  work  could  not  be  deduced  accurately  from  the  average  pressure, 
but  would  need  a  simple  application  of  the  integral  calculus  for  its  determina- 
tion. The  expression  employed  above  deviates  from  the  real  value  only  by 
about  10  per  cent.,  and  is  therefore  sufficiently  accmate  for  our  purpose. 


1032  PHYSIOLOGY 

Hg.  as  the  average  pressure  at  the  beginning  of  the  aorta,  and  500  mm. 
per  second  as  the  velocity  imparted  to  the  blood  thrown  into  the  aorta, 
we  can  calculate  the  work  done  by  the  human  heart  at  each  beat. 

QR  =  GO  X  0-100  m.  X  13-G  =  81-6  grammetres, 

or  roughly  80  grammetres.     On  the  other  hand,  the  expression 

wY^        60  X  (0-5)2 

= > — -  =  0'7  grammetres. 

2g         2  X  9-8  ^ 

It  is  evident  that  this  latter  factor  is  negligible,  and  that  for  all  practical 
purposes  we  may  regard  the  work  of  the  heart  as  proportional  to 
the  output  multiplied  by  the  average  arterial  blood  pressure.  Taking 
the  average  pressure  in  the  pulmonary  artery  at  20  mm.  Hg.,  the  work 
of  the  right  ventricle  at  each  beat  would  amount  to  about  16  gram- 
metres,  a  total  for  the  two  ventricles  of  about  100  grammetres  per 
beat,  which  is  equivalent  to  about  10,000  kilogrammetres  in  twenty- 
four  hours  for  a  man  at  rest. 

This  work  is  done  by  a  contraction  of  the  muscle  fibres  surrounding 
the  cavities  of  the  ventricles.  It  is  important  to  remember  that  the 
strain  or  tension  which  is  thrown  on  these  fibres  and  which  resists  their 
contraction  will  not  be  simply  determined  by  the  blood  pressure 
which  has  to  be  overcome,  but  also  by  the  size  of  the  ventricle 
cavities.  Since  the  pressure  in  a  fluid  acts  in  all  directions,  the  ten- 
sion caused  by  any  given  pressure  on  the  walls  of  a  hollow  vessel  will 
increase  with  the  diameter  of  the  vessel.  Thus  if  we  take  a  sphere 
with  a  radius  of  10  cm.  filled  with  fluid  at  a  pressure  of  10  cm.  Hg. 
there  will  be  a  pressure  on  each  square  centimetre  of  the  iimer  surface 
of  the  sphere  of  136  grm.  The  total  distending  force,  i.e.  the  pressure 
on  the  whole  of  the  inner  wall  of  the  sphere,  will  be  equal  to  this 
pressure  multiplied  by  the  area,  i.e.  to  136  X  4xr-  =  136  X  47r  X  100. 
If  by  a  contraction  of  the  walls  the  radius  be  reduced  to  5  cm.,  the  total 
pressure  on  the  internal  surface  will  be  reduced  to  136  X  47r  x  25, 
i.e.  will  be  one-quarter  of  the  previous  amount.  Moreover  in  the 
case  of  the  heart,  with  increasing  distension  the  wall  becomes 
thinner  and  the  number  of  muscle  fibres  in  a  given  area  fewer,  so 
that  the  larger  the  heart  the  more  strongly  will  each  fibre  have  to 
contract  in  order  to  produce  a  given  tension  in  the  contained  fluid. 
At  the  beginning  of  systole  the  distended  heart  must  therefore  contract 
more  strongly  than  at  the  end  of  systole,  in  order  to  raise  the  blood 
it  contains  to  a  pressure  sufiicient  to  overcome  that  in  the  aorta.  It 
is  evident  that  an  unrestricted  diastolic  filling  of  the  heart  is  not  of 
unqualified  advantage  to  this  organ. 

If  during  diastole  the  heart  be  too  forcibly  distended,  as  may 
easily  occur  after  opening  the  pericardium,  or  in  cases  of  enfeeble- 


THE  MErHANTSM  OF  THE  HEART  PUMP    1033 

ment  of  the  heart's  action  by  chloroform  poisoning  or  otherwise,  the 
muscle  fibres  of  the  heart  may  be  quite  unable  to  contract  against  the 
distending  force  represented  by  a  pressure  in  the  heart  equal  to  that 
in  the  aorta.  Under  such  conditions  we  may  have  sudden  heart 
failure,  which  can  only  be  relieved  by  diminishing  the  diastolic  disten- 
sion, as,  e.g..  by  letting  blood  from  the  veins  opening  into  the  heart. 


SECTION  V 

THE  FLOW  OF  BLOOD  THROUGH  THE  ARTERIES 

THE  PULSE.  0^^-ing  to  the  elasticity  and  distensibility  of  the  arterial 
wall,  the  rhythmic  rise  of  pressure  corresponding  to  each  heart- 
beat causes  an  expansion,  which  can  be  felt  by  the  finger  placed  on 
any  exposed  artery,  such  as  the  radial,  and  is  spoken  of  as  the  pulse. 
Just  as  the  blood  pressure  diminishes  from  heart  to  periphery,  so  the 
amplitude  of  the  pulse  decreases  as  we  go  farther  away  from  the  heart. 

If  the  arterial  system  were  perfectly  rigid  the  increased  pressure  due 
to  the  forcing  of  the  blood  into  the  arterial  system  at  each  ventricular 
systole  would  occur  practically  simultaneously  at  every  point.  The 
arteries  are,  however,  elastic  and  distensible,  so  that  the  first  effect  of 
the  flow  of  blood  into  the  aorta  is  to  distend  the  section  of  the  aorta 
nearest  to  the  heart.  The  elastic  reaction  of  this  forces  a  portion  of 
the  blood  into  the  nearest  section,  so  that  the  increased  pressure  is 
transmitted  from  segment  to  segment  of  the  arteries  in  the  form  of  a 
wave  at  the  velocity  of  about  seven  metres  per  second. 

It  is  important  not  to  confuse  the  velocity  of  the  pulse- wave  with 
that  of  the  blood-flow ;  the  latter  is  never  greater  than  0-5  metre  per 
second,  and  is  very  much  less  than  this  in  the  smaller  arteries.  Perhaps 
the  difference  between  the  two  quantities  may  be  made  clearer  by 
illustration  :  If  the  hindmost  of  a  row^  of  billiard-balls  be  struck 
sharply  with  a  cue  the  foremost  ball  flies  off  and  the  others  stop  still ; 
in  this  case  the  energy  imparted  to  the  first  ball  by  the  stroke  has  been 
transmitted  from  ball  to  ball,  just  as  the  effect  of  the  ventricular  con- 
traction is  transmitted  from  section  to  section  of  the  arterial  blood- 
stream. If  the  balls  are  struck  so  that  the  cue  continues  pressing  on 
the  hindmost  after  the  stroke  is  delivered,  the  front  ball  flies  off,  while  the 
others  move  slowly  along  in  the  direction  of  the  stroke.  In  the  arteries 
this  continuous  ])ressure  is  furnished  by  the  elastic  reaction  of  the 
arterial  wall,  and  we  see  how  the  impact  of  the  blood  may  travel 
quickly  as  a  wave  of  increased  pressure  while  the  blood  itself  is  moving 
slowly  along,  impelled  by  the  reaction  of  the  arterial  wall. 

If  we  imagine  a  rigid  tube  ab  (Fig.  408)  provided  with  a  piston  at 
the  end  a,  and  filled  with  an  incompressible  fluid,  an  inward  movement 
of  the  piston  at  a  will  cause  a  simultaneous  outflow  of  fluid  at  tlie  end  b. 
If  the  end  b  is  closed  the  piston  at  a  cannot  be  moved  at  all.  Pressure 

1034 


FLOW  OF  BLOOD  THROTTm  THE  ARTERIES       1035 

applied  to  the  piston  will  raise  the  pressure  simultaneously  at  all  points 
in  the  tube  ab.  The  increased  pressure  ajipliod  at  A  is  therefore 
transmitted  with  practically  no  loss  of  time  to  all  parts  of  the  tube  ab. 
This  immediate  spread  of  the  wave  of  pressure  only  applies  to  an 
incompressible  fluid  within  a  rigid  tube.  If  the  fluid  were  compressible, 
if  it  consisted,  e.g.,  of  air,  a  sudden  movement  inwards  of  the  piston  at  a 
would  not  be  felt  immediately  at  b.  The  propagation  of  the  wave  of 
pressure  from  a  to  b  would  take  a  finite  period  of  time,  its  velocity 


A 


6 


Fig.  408. 


being  identical  with  that  of  the  velocity  of  propagation  of  a  wave  of 
sound  in  air,  i.e.  1100  feet  per  second.  The  same  retarding  effect  will  be 
produced  if  we  have  an  incompressible  fluid  within  a  tube  whose  wall  is 
distensible  and  elastic.  If  we  imagine  (Fig.  409)  an  elastic  tube  bc  filled 
and  distended  with  water  and  connected  at  b  to  a  rigid  tube,  which  is 
provided  with  a  piston,  the  first  effect  of  a  rapid  movement  of  fluid 
driven  in  by  the  piston  will  be  a  rise  of  pressure  at  the  point  immediately 
in  front  of  the  piston,  viz.  at  a.  The  wall  being  distensible,  and  pres.sure 


Fig.  409. 

being  propagated  along  the  fluid  in  every  direction,  the  rise  of  pressure 
at  A  will  be  spent  partly  on  the  particles  of  fluid  in  front  of  it.  viz. 
at  6,  but  also  on  the  walls  of  the  tube,  so  that  this  is  stretched  and 
the  cross-section  of  the  tube  enlarged.  The  distended  segment  at  a 
will  then  exert,  a  pressure  on  the  contained  fluid,  driving  this  backwards 
and  forwards.  The  fluid  on  its  side  towards  the  piston  will  tend  to 
come  to  a  stop,  while  that  towards  the  distal  end  of  the  tube  will  be 
accelerated.  The  distended  wall  therefore  returns  to  its  original 
diameter,  and  the  next  segment  at  h  is  stretched  in  its  turn,  so  that 
a  wave  of  increased  pressure  is  propagated  along  the  tube  in  the  direc- 
tion of  the  arrow. 

The  velocity  with  which  this  wave  is  propagated  depends  on  the 
density  of  the  fluid,  i.e.  its  inertia,  and  on  the  resistance  of  the  walls 


1036  PHYSIOLOGY 

of  the  tube  to  distension,  since  this  will  determine  the  rapidity  of  its 
recovery.      The  velocity  of    propagation  of  the  wave  of  increased 


Fio. 


5oYVVWW\/\yvVAJ\n/\_A  n 


410.  Pulso-oiirvps  described  bj-  a  series  of  sphygmoi^rapluc  lovers 
placed  at  intervals  of  20  cm.  from  each  other  along  an  elastic  tube,  into 
which  fluid  is  forced  bj-  the  sudden  stroke  of  a  pump.  The  pulse-wave 
is  travelling  from  left  to  right,  as  indicated  by  the  arrows  over  the 
primary  (c)  and  secondary  {b,  c)  pulse-waves.  The  dotted  vertical  lines 
drawTi  from  the  summit  of  the  several  primary  waves  to  the  tuning- 
fork  curve  below,  each  complete  vibration  of  which  occupies  -V  sec, 
allow  the  time  to  be  measured  which  is  taken  up  by  the  wave  in  passing 
along  20  cm.  of  the  tubing.  The  waves  (a')  are  waves  reflected,  froui 
the  closed  distal  end  of  the  tubing  ;  this  is  indicated  by  the  direction  of 
the  arrows.  It  will  be  observed  that  in  the  more  distant  lever  (vi)  tlie 
reflected  wave,  having  but  a  slight  distance  to  travel,  becomes  fused  with 
the  primary  wave.     (From  Foster,  after  Marey.) 


pressure,  or  the  wave  of  expansion  of  the  artery,  is  expressed  by  the 
follo^vin^  formula  : 


.V 


gea 


FLOW  OF  BLOOD  THROUGH  THE  ARTERIES       1037 

where  v  is  the  velocity  per  second, 

(J,  the  acceleration  due  to  gravity, 
e,  the  elastic  coefficient  of  the  wall, 
a,  the  thickness  of  the  wall, 
d,  the  diameter  of  the  tube, 
D,  the  density  of  the  fluid, 
k,  a  constant. 

If  the  end  c  of  the  tube  is  closed,  the  wave  of  a  positive  pressure 
on  arriving  at  b  will  be  reflected  back  as  a  positive  reflected  wave.  If 
a  tracing  be  taken  of  the  oscillations  or  variations  of  pressure  in  the 
tube,  two  waves  at  least  are  seen,  one  of  which  is  the  primary  wave  due 
to  the  movement  of  fluid  caused  by  the  piston  ;    the  other  is  the 


y 


Fig.  411. 


secondary  wave  reflected  back  from  the  periphery.  The  fact  that 
the  secondary  wave  is  a  reflected  one  is  shown  by  the  fact  that  the 
nearer  to  the  peripheral  resistance  the  pulse  is  recorded,  the  nearer  is 
the  secondary  to  the  primary  wave,  as  is  seen  in  Fig.  410. 

If  the  tube  bc  be  widely  opened  a  reflected  wave  is  also  observed, 
but  this  time  of  reversed  sign,  i.e.  the  wave  is  one  of  negative  pressure. 
The  production  of  this  wave  is  dependent  on  the  momentimi  of  the 
moving  column  of  fluid.  If  in  the  tube  ab,  with  a  stop-cock  at  c  and  a 
manometer  m  (Fig.  411),  the  current  of  fluid  be  suddenly  checked  by 
turning  the  cock  c,  the  column  in  front  of  the  cock,  having  a  certain 
momentum,  will  tend  to  go  on  moving  and  therefore  produce  a  suction 
or  negative  pressure  behind  it.  When  a  wave  of  positive  pressure  arrives 
at  the  open  end  of  a  tube  there  is  a  sudden  increase  in  the  velocity  of 
output,  and  the  momentum  of  the  mass  of  fluid  which  is  thrown  out 
causes  a  similar  suction  or  negative  pressure,  which  travels  back  the 
whole  length  of' the  tube.  If  the  end  of  the  tube  is  only  partially  closed, 
every  primary  positive  wave  will  be  transformed  into  a  reflected  one 
whicli  is  partly  positive  and  partly  negative.  Since  both  these  reflected 
waves  travel  through  the  tube  with  the  same  velocity  and  will  mutually 
interfere,  the  result  may  be  either  a  positive  or  a  negative  wave  or 
nothing  at  all,  according  to  the  degree  of  constriction. 


1038  PHYSIOLOGY 

In  a  branching  system  of  tubes,  such  as  the  arterial  system,  reflec- 
tion of  waves  must  take  place  at  every  dividing  place.  All  the  condi- 
tions for  the  origin  of  reflected  waves  and  interference  of  such  waves 
are  present  in  the  arterial  system.  It  is  impossible  a  friori,  however, 
to  say  whether  any  reflected  wave  will  form  a  marked  feature  on  the 
pulse- tracing.  It  is  possible  that  the  multitudinous  reflections  which 
must  occur  in  every  part  of  the  arterial  system  may  interfere  with  any 
one  to  such  an  extent  that  they  mutually  annul  each  other.  The 
origin  of  any  secondary  wave  in  the  pulse- tracing  must  therefore  be 
determined  by  experiment. 

To  study  the  pulse  more  fully  it  is  necessary  to  obtain  a  gi-aphic 
record  of  the  expansion  of  the  arteries,  or,  what  comes  to  the  same 
thing,  of  the  exact  changes  in  pressure  which  produce  this  expansion. 
The  curve  obtained  with  the  mercurial  manometer  shows  elevations 


Fig.  412. 

corresponding  to  the  pulse  ;  but  the  instrument  is  far  too  sluggish 
to  record  the  finer  variations  of  pressure.  For  this  purpose  a 
manometer  such  as  Hiirthle's,  which  has  very  little  inertia,  must  be 
used.  The  expansion  of  the  artery  is  registered  by  means  of  a  lever, 
which  may  be  made  to  rest  more  or  less  heavily  upon  the  artery,  and 
the  movements  of  which  are  recorded  on  a  blackened  surface.  Such 
an  instrument  is  called  a  sfhygmogra'ph.  Of  the  many  forms  of 
sphygmographs,  Marey's  or  Dudgeon's  is  perhaps  the  most  con- 
venient for  clinical  purposes.    ■ 

Tlie  ])riiiciple  of  Marey's  splij'gniugrapli  is  sliouii  in  Fig.  412.  Tho  button  h 
is  atljustfd  HO  as  to  press  on  the  radial  artciy.  Its  movcmonts  are  transmitted 
to  a  lever  m.  The  screw  on  tliis  works  on  a  small  cogged  wheel  at  o,  which  is 
also  the  axis  of  the  writing  lever  I.  The  movements  of  the  button  h  thus  trans- 
mitted to  a  point  near  tlie  axis  of  I  are  reproduced  by  this  lever  liighly  magnified, 
and  as  such  are  recorded  on  a  blackened  surface.  The  pressure  on  the  artery  can 
be  adjusted  by  means  of  a  screw. 

Dudgeon's  sphygmograph  (Fig.  413)  is  ratlier  easier  to  use  than  Marey's, 
and  is  tlierefore  largely  employed  for  clinical  purjjoses.  It  i§  provided  witli  a 
dial  by  Mliicli  the  pressure  on  the  artery  can  be  graduated,  and  has  a  small 
clockwork  arrangement  for  moving  along  the  slip  of  smoked  paper  on  which  the 
records  are  taken.  The  arrangement  of  the  levers  in  this  form  of  sphygmograph 
is  shown  in  Fig.  414,  where  f  is  the  (adjustable)  sjjring  bearing  by  its  button  P 
on  the  artery.  The  up-and-down  movements  of  r  are  transmitted  to  s,  being 
much  magnified  and  converted  into  side-to-side  movements.  The  point  of  s 
rests  on  the  blackened  surface  represented  in  section  at  a,  and  scratches  on  this, 


FLOW  OF  BLOOD  THROUGH  THE  ARTERIES       1039 

when  moving,  a  magnified  record  of  the  expansion  of  the  artery  under  the 
knob  r. 

Either  form  of  sphygruogiaph  is  generally  applied  to  the  radial 
artery,  since  this  is  near  the  surface  and  is  supported  by  bone,  and  the 
arm  is  well  adapted  for  the  application  of  the  sphygmograph.     The 


Fig.  413. 


Dudgeon's  sphygmograph,  showing  its  mode  of  application  to 
the  radial  artery. 


pulse- curve  obtained  by  means  of  a  sphygmograph  varies  according 
to  the  artery  employed  and  the  force  wth  which  the  lever  presses  on 
the  artery,  but  all  the  curves  present  the  same  general  features. 

The  velocity  of  the  pulse  can  be  measured  by  taking  simultaneous 
tracings  from  two  arteries  separated  by  some 
distance  from  one  another,  such  as  the  femoral 
artery  and  the  dorsalis  pedis,  or  from  the  carotid 
and  radial  arteries.  In  a  healthy  individual  the 
velocity  varies  between  7  and  10  metres  per 
second.  The  more  rigid  the  arteries  the  greater 
will  be  the  velocity,  so  that  the  velocity  of 
propagation  gradually  increases  with  advancing 
age,  and  is  higher  in  the  arteries  of  the  lower 
extremities  tlum  in  the  more  distensible  arteries 
of  the  arm. 

The  length  of  the  pulse-wave  can  be  found 
by  umltiplying  the  velocity  of  transmission  by 
the  time  occupied  by  the  wave  in  passing  any 
given  point.  The  duration  of  the  wave  at  any  point  corresponds  to 
the  time  of  a  cardiac  cycle,  viz.  0-8  sec,  so  that  if  the  velocity  of 
transmission  be  taken  as  7  metres  per  second,  the  length  of  the  wave 
is  about  5-G  metres.     The  pulse-wave  thus  reaches  the  periphery  long 


Fiti.  414.  DiagraiiJ  i>f 
anaugiiiu'nt  of  rv- 
lording  lever  hi 
Dudgeon's  sphygmo- 
graph. 


1040  PHYSIOLOGY 

before  it  has  been  completed  in  the  aorta.  Fig.  415  represents  a  pulse- 
curve  taken  from  the  radial  artery.  The  elevation  due  to  the  expan- 
sion of  the  artery  is  rapid  and  uninterrupted.  We  have  already 
explained  that  this  is  due  to  the  sudden  pumping  of  blood  into  the  first 
part  of  the  aorta,  whence  the  impulse  is  transmitted  as  a  wave  along 
the  arteries.  The  curve  descends  gradually  till  the  next  beat  occurs, 
since  the  elastic  reaction  of  the  arteries,  which  tends  to  keep  up  the 
pressure,  acts  more  constantly  and  steadily  than  the  heart-beat.  On 
this  descending  part  of  the  curve  occur  two  or  three  secondary  eleva- 
tions :  h  is  the  primary  or  '  percussion  '  wave,.c  the  pre-dicrotic  or 
'  tidal '  wave,  and  e  the  dicrotic  wave.  Elevations  may  occur  on  the 
curve  after  e  which  are  called  post-dicrotic  waves.  It  is  better  to 
class  the  elevations  before  the  dicrotic  notch  d  as  systolic  elevations, 
and  those  afterwards,  including  the  dicrotic  elevation  itself,  as  diastolic. 


Fig.  415.     Pulse-curve  from  radial  artery. 

For  the  exact  understanding  of  these  elevations  it  is  necessary  to  take 
simultaneous  tracings  of  the  pressures  in  the  left  ventricle  and  in  the 
aorta  (Figs.  416,  417).  In  this  w^ay  we  may  dissociate  the  waves  caused 
by  the  ventricular  systole  from  those  having  their  origin  in  the  aorta. 
In  Fig.  416  are  represented  typical  tracings  of  cardiogram,  intraventri- 
cular pressure,  and  aortic  pressure,  taken  simultaneously.  The  dotted 
lines  are  drawn  through  synchronous  parts  of  the  curve.  Considering 
first  the  dotted  part  of  curve  II  and  curve  IV,*  we  see  that  the  contrac- 
tion of  the  ventricle  begins  at  a  ;  the  rise  of  intraventricular  pressure 
from  A  to  B  is  without  effect  on  the  aortic  pulse  ;  at  b  the  intra- 
ventricular is  exactly  equal  to  the  aortic  pressure,  and  then  rapidly 
rises  above  it.  Since  the  aortic  valves  offer  no  resistance  to  the  flow  of 
blood  from  ventricles  to  aorta,  they  must  open  so  soon  as  the  intra- 
ventricular exceeds  the  aortic  pressure,  and  this  is  shown  to  be  the  case 
by  the  rise  of  pressure  in  the  aorta.  From  b  to  c  the  ventricle  is  still 
contracting  and  forcing  the  blood  into  the  already  distended  aorta, 
so  causing  a  rise  of  pressure.  At  c  the  ventricle  relaxes,  the  intra- 
ventricular pressure  falls  quickly,  and  at  d  has  fallen  below  the  aortic 
pressure.  The  aortic  valves  must  now  close,  since  the  pressure  is 
greater  on  their  aortic  side.     The  fall  of  pressure  on  the  ventricle  now 

*  Cui'vo  IV  in  Fig.  410  must  bo  Lujii2)Hrcd  with  tJie  pulse  tracing  from  (lio 
radial  artery  in  Fig.  415.  It  will  be  Been  that,  a])art  from  the  fact  that  Fig.  410 
IV  is  rflorc  lengthened  out  than  Fig.  415  o\Aiiig  to  the  great  rapidity  of  the 
recording  apparatus,  the  curvoB  ai'e  practically  similar. 


FLOW  OF  BLOOD  THROUGH  THE  ARTERIES       1041 

goes  on  uninterruptedly,  but  in  the  aorta  there  is  a  sharp  elevation 
imniediately  after  d.  This  elevation  is  the  dicrotic  wave.  We  thus  see 
that  it  comes  imniediately  after  closure  of  the  aortic  valves. 


AB 


C  0 


r  D 


u.:j 
Diastole 


A  B 


Fig.    41(i.  Diagram  (after  Hurthle)  showing  simultaneous  cardiographic 

endocardiac,  and  aortic  curves. 

I,  cardiogram  ;  ii,  endocardiac  pressure  ;  III,  aortic  pressure  :  iv,  aortic 

pressure,  corresponding  to  dotted  endocardiac  curve  in  ii. 


There  are  several  factors  at  work  tending  to  produce  a  secondaiy 
wave  at  this  point.  With  the  sudden  cessation  of  the  inflow  of  blood 
from  the  ventricles  at  the  end  of  the  ventricular  contraction  a  negative 
wave  must  be  produced  at  the  beginning  of  the  aorta,  which,  trans- 
mitted along  the  arterial  system,  will  tend  to  produce  a  reflux  of  blood 
to\\:ards  the  heart.  The  movement  so  caused  is  reinforced  by  the  elastic 
Reaction  of  the  arterial  wall  so  that  the  retuniing  blood  is  driven  up 

66 


1042 


PHYSIOLOGY 


against  the  aortic  valves,  closing  them  tightly  and  putting  them  on  the 
stretch.  Even  in  a  rigid  tube  the  sudden  cessation  of  flow  causes  a  nega- 
tive wave,  followed  by  a  positive  wave  in  the  opposite  direction  in  the 
aorta  ;  this  positive  wave  is  increased  by  the  elastic  reaction  of  the 
stretched  aortic  valves.  The  blood  is  driven  up  against  them  by 
the  wave  of  positive  pressure  and  then  rebounds,  like  a  billiard  ball 
from  the  elastic  cushion,  and  gives  rise  to  the  dicrotic  elevation. 
That  the  dicrotic  elevation  is  for  the  most  part  a  positive  wave 
running  in  a  centrifugal  direction  is  shoA\ai  by 
the  fact  that  the  distance  between  it  and  the 
primary  wave  does  not  alter  appreciably  from 
whatever  part  of  the  arterial  system  the  tracing 
be  taken.  If  it  were  a  reflected  wave  the  dis- 
tance between  it  and  the  primary  elevation  of 
the  pulse -curve  ought  to  be  less  the  nearer  the 
periphery  the  pulse  tracing  is  taken. 

The  pre-dicrotic  waves  are  to  be  ascribed  to 
elastic  oscillations  set  up  in  the  beginning  of  the 
arterial  system  by  the  sudden  rise  of  pressure. 
Just  as  an  india-rubber  ball  allowed  to  drop 
on  to  the  gTOund  wall  bounce  several  times 
before  it  comes  to  rest,  so  any  sufiiciently 
sudden  rise  of  pressure  in  an  elastic  fluid  system 
must  give  rise  to  a  series  of  oscillations  whether 
the  fluid  is  moving  or  not.  There  is  no  doubt 
that  the  pre-dicrotic  elevations  as  usually  repre- 
sented are  much  distorted  by  the  peculiarities 
of  the  instrument  used.     In  the  tracing  of   the 


Vehtricle 


Ventricle 


Fig.  417.  intraventricu- 
lar and  aortic  pressure 
curves  of  a  clog  taken  by 

means  of  the  capillary   aortic  pressure    by  Frank    there  is   only   one 

and  S™AKUNG  )  ^^'^^^   primary  elevation  on  the  ascending  part  of  the 

curve     where    the    ascent    suddenly    becomes 

less  steep.     In  the  same  way  the  post-dicrotic  elevations  may  be 

regarded  as  a  dying  away  of  the  dicrotic  wave  more  or  less  distorted 

by  instrumental  vibrations. 

The  general  form  of  the  pulse-curve  varies  with  changes  in  the 
heart,  in  the  arteries,  and  in  the  peripheral  resistance.  Thus  some 
curves  may  present  secondary  elevations  on  the  ascending  part,  as  in 
Fig.  416,  III,  and  are  called  anacrotic,  while  in  others  all  secondary 
elevations  occur  on  the  descending  part.  This  latter  type  is  called 
catacrotic,  and  is  the  tracing  usually  obtained  from  a  normal  radial 
artery.  By  comparing  these  two  types  of  curves  with  the  correspond- 
ing intraventricular  pressures,  we  find  that  in  both  cases  blood  is 
flowing  into  the  aorta  during  the  whole  time  from  the  beginning  of  the 
primary  elevation  to  the  notch  just  before  the  dicrotic  elevation. 


FLOW  OF  BLOOD  THROUGH  THE  ARTERIES       1043 

This  is  shown  by  the  fact  that  the  intraventricular  pressure  is  all  this 
time  slightly  higher  than  the  aortic  pressure.  So  long  as  this  is  the 
case  blood  must  flow  from  ventricle  into  aorta.  (This  fact  proves  that 
there  is  normally  no  part  of  the  cardiac  cycle  during  Avhich  the  ventricle 
remains  contracted  and  empty,  the  ventricle  in  all  cases  relaxing  before 
it  has  completely  emptied  itself  of  blood.) 

Now  it  is  easy  to  see  the  conditions  which  determine  whether  the 
systolic  plateau  shall  be  ascending  or  descending,  and  therefore  when 
the  pulse  shall  be  anacrotic  or  catacrotic.  If,  after  the  first  sudden 
rise  of  pressure  in  the  aorta,  the  blood  can  escape  more  rapidly  through 
the  peripheral  resistance  than  it  is  thrown  into  the  beginning  of  the 
aorta,  the  systolic  plateau  ^^^ll  sink,  and  a  catacrotic  pulse  tracing  is 
obtained.  If,  on  the  other  hand,  the  peripheral  resistance  is  high,  or 
an  extra  large  amount  of  blood  be  thrown  into  the  aorta  at  each  stroke 
of  the  heart  [e.g.  by  prolongation  of  the  diastole),  the  aortic  pressure 
will  rise  so  long  as  blood  is  flowing  in,  and  we  get  an  ascending  systolic 
plateau  and  an  anacrotic  pulse.  Thus  we  obtain  an  anacrotic  pulse  in 
old  people  with  Bright's  disease,  in  whom  the  peripheral  resistance  is 
very  high,  and  also  in  animals  when  the  heart  is  slowed  by  vagus 
action. 

The  production  of  the  dicrotic  elevation  is  favoured  by  any  influence 
which  increases  the  elastic  resiliency  of  the  arteries  or  causes  the 
primary  elevation  of  the  pulse  to  be  rapid  and  sharp.  Thus  it  is  much 
more  pronounced  in  young  people  than  in  old  people,  whose  arteries 
have  become  rigid.  Where  the  peripheral  resistance  is  low  through 
relaxation  of  the  arterioles,  and  the  heart  is  beating  forcibly,  as  in 
many  cases  of  fever  and  also  to  some  extent  after  a  good  meal  with 
alcohol,  the  dicrotic  elevation  becomes  very  marked.  Lender  such 
circumstances  it  may  be  easily  felt  with  the  finger  at  the  wrist,  and  in 
many  cases  the  mistake  has  been  committed  of  taking  the  dicrotic 
wave  for  a  normal  beat,  and  so  doubling  the  rate  of  the  pulse. 

OTTO  FRANK'S  WORK  ON  THE  PULSE.  In  the  account  given  above  of  the 
peculiarities  of  the  pulse-curve  in  different  parts  of  the  system  I  have  adopted 
in  the  main  the  views  of  Marey  and  Hiirthle.  whicli  have  been  generally  accepted 
for  a  considerable  time  and  have  influenced  most  of  the  clinical  work  on  this 
subject.  According  to  these  authors  all  the  secondarj'  waves  on  the  pulse-curve 
are  central  in  origin,  and  can  therefore  be  traced  with  slight  moditication  on  the 
curves  obtained  from  the  aorta,  the  large  and  the  small  arteries.  Although 
Marey  investigated  the  propagation  of  reflected  waves  and  showed  their  presence 
in  the  artificial  schema  of  the  circulation  (v/rfe  p.  1036),  he  considered  that  they 
could  not  contribute  to  the  production  of  the  waves  on  the  pidse-ciu"ve,  owing 
to  the  enormous  number  of  points  at  which  reflection  might  occiu".  so  that  the 
different  reflected  waves  woiUd  tend  to  mutually  annul  each  other's  cffcct^s. 
Moreover  the  distance  of  the  dicrotic  notch  from  the  primary  elevation  was 
found  to  be  nearly  the  same  at  different  parts  of  the  system,  pointing  to  a  propa- 
gation of  this  wave  from  the  centre  to  the  circumference  of  the  arterial  system. 


1044 


PHYSIOLOGY 


Frank  has  pointed  out,  in  the  first  place,  that  all  the  instruments  hitherto  used , 
including  the  manometers  of  Hiirthle,  are  not  nearly  delicate  enough  to  register 
the  very  rapid  changes  of  pressiire  which  occur  in  the  heart  at  the  beginning  of 
the  arterial  system.  The  best  instruments  hitherto  used,  as  applied  to  the  body — 
i.e.  with  their  connecting  tubes,  cannula,  &c. — possess  an  instrumental  vibra- 
tion frequency  of  not  more  than  10  to  15  per  second.  If  we  consider  that  the 
systole  of  a  rabbit's  heart  beating  over  200  times  per  minute  may  last  less  than  a 
tenth  of  a  second,  we  see  that  the  curve  of  endocardiac  pressure  obtained  by  such 
instruments  would  be  seriously  deformed  by  the  vibrations  set  up  in  the  instru- 
ment itself.  The  manometer  of  Frank  described  above  has  a  vibration  frequency 
of  180  per  second.  This  efficiency  is  attained  by  getting  rid  of  the  recording  lever, 


Fig.  418.     Four  different  types  of  pulse  curve,  from  the  radial  artery. 

(Mackenzie.) 

These  were  taken  from  a  patient  during  recovery  from  an  attack  of  acute 
dilatation  of  the  heart.  Note  the  gradual  rise  in  the  height  of  the  systolic 
notch.     No.  4  was  taken  after  complete  recovery. 

using  a  beam  of  light  for  this  purpose,  by  having  a  short  wide  tube  connecting 
the  manometer  with  the  interior  of  the  artery,  by  avoiding  all  rubber  connections, 
and  by  scrupulous  exclusion  of  air  bubbles  in  the  apparatus. 

A  similar  apparatus  has  been  employed  by  Straub,  The  results  obtained  by 
these  methods  may  be  shortly  summarised  as  follows  : 

(o)  The  curve  of  endocardiac  pressure  in  the  ventricle  is  quite  simple  and 
similar  to  the  contraction  curve  of  a  voluntary  striated  muscle  (Straub).  There 
is  no  systolic  plateau,  nor  are  there  any  superposed  vibrations.  The  systolic 
vibrations  are,  according  to  Frank,  entirely  instrumental  in  origin. 

[h)  The  aortic  pressure  curve  (Fig.  419)  is  also  rounded  at  the  top.  It  presents 
one  set  of  vibrations  during  the  systole  at  the  point  where  the  very  rapid  rise  of 
pressure  begins  to  slow  off.  A  second  depression  followed  by  an  elevation  signalises 
the  beginning  of  relaxation  of  the  ventricle,  with  a  slight  back-flow  of  blood  on 
to  the  aortic  valves  and  the  rebound  from  these  valves  as  they  are  closed  by 
the  regurgitant  wave.  At  the  end  of  the  diastolic  descent  of  the  curve  are 
some  small  vibrations  which  mark  the  beginning  of  the  ventricular  contrac- 
tion.   The  sudden  rise  of  pressure  in  the  ventricles,  even  before  the  aortic  valves 


FLOW  OF  BLOOD  THROUGH  THE  ARTERIES       1045 

open,  sets  these  structures  into  vibration  and  so  causes  the  fine  oscillations  of 
pressurfi  on  the  aortic  side  of  the  valves. 

(c)  The  Peripheral  Puhe.  The  cfTect  of  the  propagation  of  the  fairly  simple 
wave  started  in  the  aorta  in  an  endless  system  of  elastic  tubes  would  be  to 
diminish  the  rapidity  of  onset  of  each  vibration,  and  therefore  to  diminish  the 
secondary  vibrations  on  the  ciuve.  In  a  closed  elastic  system  of  tubes,  such 
as  the  arterial  system,  there  will  be  factors  at  work  analogous  in  many  respects 
to  those  responsible  for  the  deformation  of  the  curve  given  by  an  imperfect 
iiiaiionicter.   These  will  be  of  two  kinds,  namely,  (1)  oscillations  of  the  column  of 


Fig.   419.     Pulse-pressure  curves  taken  by  means  of  Frank's  manometer. 

(Frank.) 
A,  B,  c,  aortic  pressure  curves  at  different  rates  of  the  heart ;  D  and  E,  aortic 
pressiue  curve,  d,  compared  with  simultaneous  record  of  the  pressure  in  the 
femoral  artery  E. 


fluid  within  the  stretched  arterial  wall,  (2)  reflections  of  waves  from  different 
points  in  the  periphery.  These  reflections  we  should  expect  to  be  evident  in  certain 
cases.  Thus  in  the  carotid  there  should  be  a  reflected  wave  from  the  circle 
of  Willis  ;  in  the  descending  aorta,  from  the  bifiucation  of  this  vessel  into  the 
two  iliac  arteries.  As  a  result  the  pulse  in  the  peripheral  arteries,  such  as  the 
radial  or  femoral,  diverges  considerably  from  the  piUse  in  the  aorta.  In  the  figure 
(Fig.  419  e)  the  primary  rise  of  pressure  in  the  femoral  arterj^is  even  higher  than 
the  primary  rise  in  the  aorta,  i.e.  the  primary  wave  must  be  augmented  here  by  a 
reflected  wave  from  the  periphery.  Frank  acknowledges  that  the  dicrotic  depres- 
sion in  this  curve  is  due  to  the  propagation  of  the  wave  set  up  by  the  closure  of  the 
aortic  valves  ;  but  he  would  regard  the  more  pronounced  diorotism  of  the  pulse, 
of  which  examples  have  been  given  earlier,  as  due  for  the  most  part  to  the  reflec- 
tion of  waves  from  the  periphery. 


1046  PHYSIOLOGY 

From  time  immemorial  the  physician  lias  sought  by  feeling  the 
pulse  to  come  to  some  idea  as  to  the  condition  of  the  circulation.  A 
number  of  different  qualities  have  therefore  been  distinguished. 
According  to  the  number  of  beats  per  minute  the  pulse  is  distinguished 
as  frequent  or  rare.  The  size  of  the  pulse  has  reference  to  the  amplitude 
of  excursions  of  each  beat  and  the  pulse  is  distinguished  as  large  or 
small.  The  velocity  of  the  pulse  expresses  the  speed  with  which  the 
excursion  is  accomplished.  The  quick  pulse  is  one  in  which  the  artery 
presses  against  the  finger  suddenly  and  then  disappears  suddenly, 
while  in  the  slow  pulse  the  period  during  which  pressure  can  be  felt 
is  more  prolonged.  The  hardness  of  the  pulse  is  determined  chiefly 
by  the  blood  pressure.  If  the  pulse  is  compressible  it  is  spoken  of  as 
soft ;  if  it  can  only  be  obliterated  with  difficulty  it  is  liard.  Certain 
combinations  of  these  quafities  are  also  described.  Thus  a  large  and 
hard  pulse  is  spoken  of  as  strong,  a  weak  pulse  being  both  small  and 
soft.  A  small  hard  pulse  is  called  contracted.  If  the  rhythm  of  the 
heart-beat  is  irregular  the  pulse  is  also  irregular.  An  intermittent 
pulse  is  one  in  which  one  heart-beat  is  dropped  occasionally,  i.e.  once 
in  every  four  or  eight  beats,  and  may  be  due  to  the  interposition  of 
a  ventricular  contraction  which  is  too  weak  to  send  the  pulse  along  so 
far  as  the  radial  artery. 

Judgments  as  to  the  conditions  of  the  heart  and  circulation  from 
the  feehng  of  the  pulse  oscillations  must,  however,  be  made  with 
extreme  caution.  The  pulse-curve  may,  indeed,  give  approximate 
information  as  to  the  condition  of  things  in  the  heart.  Thus  the 
period  between  the  beginning  of  the  primary  elevation  and  the  di- 
crotic notch  corresponds  to  the  outflow  of  blood  from  ventricle  to  aorta. 
A  large  pulse-curve  does  not  necessarily  indicate  a  big  output,  since 
the  expansion  of  the  artery  is  determined  not  only  by  events  occurring 
in  the  aorta  but  also  by  the  tonus  of  the  artery  under  the  finger  and 
the  resistance  in  the  peripheral  branches. 

Perhaps  the  best-marked  condition  of  the  pulse  is  that  known  as 
the  '  water-hammer '  pulse,  which  is  observed  in  cases  where  the  aortic 
valves  are  injured  or  diseased  so  as  to  allow  of  regurgitation  into  the 
ventricle.  The  systolic  rise  of  pressure  in  the  arterial  system  is  followed 
by  an  extremely  rapid  fall,  so  that  towards  the  end  of  diastole  the 
pressure  in  the  arteries  may  be  insufficient  to  keep  the  arterial  system 
filled.  Under  such  conditions,  if  the  arm  be  held  above  the  head 
and  the  wrist  of  the  patient  be  grasped,  the  pulse  in  the  arteries 
of  the  wrist  is  felt  as  a  smart  blow  coinciding  with  each  beat  of  the 
heart. 


FLOW  OF  BLOOD  THROUGH  THE  ARTERIES       1047 

THE  CIRCULATION  THROUGH  THE  CAPILLARIES 

The  capillary  circulation  is  most  easily  studied  by  examining 
under  the  microscope  the  tongue  of  the  frog  or  the  web  of  the  frog's 
foot.  Under  a  power  of  about  150  to  180  diameters  a  network  of 
vessels  is  seen,  consisting  of  small  arteries,  capillaries,  and  veins.  The 
direction  of  flow  in  the  arteries  is  opposite  to  that  in  the  veins.  In 
the  capillaries  the  flow  is  from  arteries  to  veins,  though,  on  account 
of  the  reticular  arrangement  of  these  vessels,  the  direction  of  the 
stream  through  them  is  not  quite  constant  and  may  occasionally  be 
reversed.  The  flow  of  blood  in  the  arteries  is  rapid,  whereas  in  the 
veins  it  is  generally  possible  to  distinguish  the  individual  blood-cor- 
puscles. Through  the  capillaries  the  flow  is  very  inconstant.  If  a 
group  of  capillaries  be  watched  for  some  time  the  blood  may  at  first 
hurry  through  a  number  of  them  with,  great  rapidity  ;  the  flow  then 
becomes  slower  and  then  may  quicken  up  to  a  moderate  pace  again. 
These  variations  in  the  capillary  flow  are  probably  associated  with 
spontaneous  alterations  in  the  condition  of  contraction  of  the  small 
arteries  supplying  the  group  of  capillaries.  It  is  easy  to  observe  that 
the  arterial  flow  is  pulsatile,  the  pulsation  disappearing  in  the  capil- 
laries and  veins.  Another  difference  between  the  circulation  in  these 
three  kinds  of  vessels  is  to  be  found  in  the  condition  of  the  peripheral 
zone.  In  the  arteries  the  blood-stream  is  divided  into  two  parts,  the 
peripheral  stream — about  "01  mm.  wide,  consisting  only  of  colourless 
plasma  with  occasionally  a  stray  leucocyte — and  an  axial  stream,  in 
which  all  the  red  blood-corpuscles  are  being  hurried  along.  In  the  veins 
there  is  a  similar  peripheral  plasmatic  zone,  but  here  we  find  regularlv 
scattered  leucocytes  which  travel  rather  more  slowly  than  the  axial 
stream  of  red  corpuscles.  The  formation  of  this  axial  zone  is  purely 
mechanical,  and  may  be  imitated  in  any  fluid  containing  in  suspension 
particles  whose  specific  gravity  is  somewhat  higher  than  that  of  the 
fluid.  In  the  capillaries  there  is  no  separation  of  the  two  zones,  since 
the  lumen  of  these  vessels  as  a  rule  allows  only  the  passage  of  one  or 
two  corpuscles  abreast,  so  that  they  are  everywhere  in  contact  witli 
the  wall.  The  corpuscles  are  evidently  elastic  structures,  and  may  be 
seen  to  bend  if  they  impinge  on  the  dividing  point  of  two  capillaries 
before  they  are  finally  swept  of?  by  the  stream  into  one  or  the 
other. 

The  capillary  wall  is  composed  of  a  single  layer  of  elongated 
flattened  cells  which  present  little  resistance  to  the  passage  through 
thera  by  diftusion  of  dissolved  substances,  such  as  sugar,  salts,  oxygen, 
or  carbon  dioxide.  In  this  way  the  tissue-colls  obtain  oxygon  from  the 
red  bl()od-corj)us('los  and  nutriment  from  the  ])lasina,  and  give  off 
to  the  circulating  blood  carbon  dioxide  and  otlior  effete  substances 


1048  PHYSIOLOGY 

as  tlie  products  of  their  metabolism.  There  is  evidence  that  in  some 
situations  the  cells  forming  the  capillary  wall  may  be  contractile. 
According  to  Strieker  and  others,  the  cell  substance  is  arranged  in 
strands  running  from  the  nuclei  around  the  capillary.  By  the  con- 
traction of  these  strands  the  vessel  may  be  narrowed  to  obliteration. 
These  phenomena  have  been  observed  in  the  nictitating  membrane 
of  the  frog,  but  it  is  doubtful  how  far  they  may  be  extended  to  the 
other  capillary  systems  of  the  body.  If  the  contractile  power  is  at  all 
universally  present,  it  must  play  an  important  part  in  determining  the 
amount  of  blood-flow  through  the  capillaries  of  an  organ,  and  will 
doubtless  be  largely  affected  by  chemical  substances 
produced  as  the  result  of  the  metabolism  of  the  sur- 
rounding tissues. 

The  average  length  of  a  capillary  is  between  0*4  and 
0*7  mm.  The  velocity  of  blood-flow  can  be  directly 
determined  by  observing  under  the  microscope  the 
time  taken  by  any  given  corpuscle  to  travel  a  measured 
distance  on  the  microscope  stage.  The  mean  velocity 
determined  in  this  way  varies  from  about  0*5  to  0*8  mm. 
per  second.  Since  the  red  corpuscles  travel  in  the 
Fig.  420.  Ap-  axial  part  of  the  stream,  the  mean  velocity  of  the  total 
Kii'es  for  mea-  blood  wiU  be  rather  smaller,  and  may  be  taken  at  about 
snring  capillary  Q'S  mm.  per  second. 

The  blood  pressure  in  the  capillaries  may  be 
measured  approximately  by  applying  pressure  to  the  outer  surface  of 
the  skin  or  mucous  membrane  and  noticing  the  point  at  which 
blanching  of  the  surface  is  produced. 

In  von  Kries'  method  a  small  glass  plate,  from  2  to  5  sq.  mm.  in  area,  is 
placed  on  the  last  joint  of  the  finger.  Attached  to  tliis  glass  plate  is  a  small  scale 
pan  on  wliich  Aveights  arc  placed  until  the  pressure  is  just  sufficient  to  blanch 
the  underlying  skin.  In  using  this  method  the  calculation  of  the  capillary  pressure 
is  made  as  follows  : 

Supposing  that  the  size  of  the  glass  plate  is  4  sq.  mm.  and  1  grm.  in  the  scale 
pan  is  just  sufficient  to  cause  a  change  of  colour  in  the  skin,  then 

a  weight  of  1  grm.  =  1  c.c.  HgO  =  1000  c.mm.  H2O 

is  present  on  an  area  of  4  sq.  mm.    The  height  of  the  column  of  water  supported 

by  1  sq.  mm.  is  therefore  =  250  mm.  H2O.    The  errors  of  this  method  are 

considerable,  since  the  pressure  thus  determined  is  not  the  total  capillary 
pressure,  but  this  minus  the  pressure  in  the  tissue  spaces  on  the  outer  side  of  the 
capillary  wall.  Ilie  result  will  therefore  vary  not  only  with  capillary  pressure 
but  also  with  the  tension  of  the  skin  and  the  amount  of  fluid  in  the  tissue 
spaces. 

Tlie  pressure  in  the  capillaries  as  found  by  this  method  necessarily  varies 
with  the  position  of  the  part  under  investigation,  i.e.  with  the  hydrostatic  pressure 


FLOW  OF  BLOOD  THROUGH  THE  ARTERIES       1049 

of  the  column  of  blood  between  it  and  the  lieart.     Tlie  following  figures  were 
found  by  von  Kries  : 


Finger  :      Mm.  H,0 

Distance  of  finger 

below  head 

328 

0  mm. 

329 

, . 

205  mm. 

513 

, . 

490  mm. 

738 

840  mm. 

Ear  :  20  mm.  Hg. 

Gums  of  Rabbit :  33 

mm 

•  Hg. 

Frog's  Web  (Roy) : 

100- 

150  mm. 

HoO. 

Capillary  venovis  pressure  of  brain  (Hill) : 

(1)  Animal  in  horizontal  position  :    10  mm.  Hg. 

(2)  „       „    feet-down  position  :    zero  or  less. 

(3)  During  strychnine  conrulsions  :  50  mm.  Hg. 

Owing  to  the  fact  that  a  varying  and  unknown  resistance — that 
of  the  arterioles — lies  between  the  capillaries  and  the  arteries,  Jjie 
pressure  in  the  capillaries  must  stand  in  much  closer  relationship  to 
that  in  the  veins  than  to  that  in  the  arteries.  One  cannot  therefore 
argue  that  a  fall  of  arterial  pressure  necessarily  involves  a  fall  of 
capillary  pressure  in  all  parts  of  the  body.  We  can  only  judge  of 
changes  in  the  capillary  pressure  by  taking  simultaneously  the  pressures 
in  both  the  afferent  and  efferent  vessels.  If  these  both  rise  or  fall 
together  we  may  be  certain  that  the  capillary  pressure  also  rises  or 
falls.  Where  the  arterial  and  venous  pressures  move  in  opposite  direc- 
tions it  is  difficult  to  say  what  alterations,  if  any,  will  be  produced  in 
the  capillary  pressure. 

The  resistance  to  the  flow  of  blood  through  the  capillaries  is  deter- 
mined by  the  internal  friction,  i.e.  the  viscosity  of  the  blood  ;  this 
varies  in  different  animals  between  three  and  five  times  that  of  water. 
It  has  been  calculated  that  the  fall  of  pressure  undergone  by  the  blood 
in  passing  through  any  given  capillary  area  is  only  about  20  to  60  mm. 
of  blood,  and  at  the  most  is  never  more  than  150  mm.  blood,  i.e. 
about  10  mm.  Hg.  Tliis  bears  out  the  conclusion  to  which  we  have 
already  come,  viz.  that  the  chief  seat  of  the  resistance  in  the  vascular 
system  is  the  arterioles,  and  it  is  in  this  region  that  the  chief  fall  of 
pressure  occurs. 


SECTION  VI 

THE  FLOW  OF  BLOOD  IN  THE  VEINS 

In  the  veins  there  is  a  constant  decrement  of  pressure  as  we  pass 
from  the  periphery  towards  the  heart.  This  decrement  of  pressure 
is  the  consequence  of  the  pumping  action  of  the  heart,  so  that  the 
flow  through  the  veins  must  be  ascribed  to  the  same  force  as  that 
which  determines  the  flow  through  the  arteries,  viz.  the  heart-beat. 
Owing  to  the  fact  that  no  appreciable  resistance  lies  between  the  veins 
and  the  heart,  the  difierence  of  pressure  necessary  to  maintain  a 
constant  flow  through  these  vessels  is  very  small.  Thus  in  the  hori- 
zontal position  the  pressure  in  the  femoral  veins  may  be  from  5  to 
10  mm.  Hg.,  and  in  the  inferior  vena  cava  from  1  to  5  mm.  The  pres- 
sure in  the  great  veins  near  the  heart  is  generally  negative  owing  to  the 
aspiration  of  the  thorax,  and  this  negative  pressure  is  naturally 
increased  during  inspiration.  Opening  the  thorax  therefore  causes 
a  rise  of  pressure  in  all  the  large  veins.  In  the  latter  the  pressure 
depends  chiefly  on  the  heart  activity,  being  lowered  by  vigorous  action 
of  the  heart  pump  and  raised  when  this  fails  in  any  way.  In  the  peri- 
pheral veins  the  pressure  is  more  dependent  on  the  flow  through  the 
corresponding  arteries.  If  an  artery  of  a  limb  be  ligatured  the  pressure 
in  the  small  veins  of  the  limb  sinks  until  it  is  reduced  to  the  pressure 
in  the  nearest  large  trunk  in  which  a  flow  of  blood  continues. 

Each  cardiac  cycle  causes  variations  in  the  pressure  in  the  great 
veins  next  the  heart  in  two  ways  : 

(1)  By  the  transmission  along  the  veins  of  the  alterations  in  the 
intra -auricular  pressure. 

(2)  By  the  diminution  in  the  volume  of  the  heart  in  consequence 
of  the  expulsion  of  its  blood  along  the  arteries  with  each  heart-beat. 

On  this  account  the  jugular  veins  show  pulsations  with  each  heart- 
beat which  are  somewhat  complex  in  character  and  resemble  closely 
those  occurring  in  the  auricle  {vide  p.  1015).  In  Fig.  421  a  tracing  from 
the  wall  of  the  jugular  vein  is  given.  It  will  be  seen  that  each  heart- 
beat gives  rise  to  three  variations  in  pressure  within  the  veins.  These 
three  undulations  are  evidently  exactly  analogous  to  those  given  in 
the  diagram  on  p.  101(5  as  occurring  in  the  auricular  tracing.  We  should 
therefore  regard  a  as  the  auricular  contraction,  c  as  the  elevation  due 

to  the  closure  of  the  auriculo-ventricular  valves,  v  as  the  elevation  due 

1050 


THE  FLOW  OF  BLOOD  IN  THE  VEINS  1051 

to  the  accumulation  of  blood  in  the  auricles  during  the  ventricular 
systole.  The  curve  c  is  often  spoken  of  as  the  carotid  elevation,  and 
has  been  ascribed  by  Mackenzie  to  direct  propagation  to  the  jugular 
vein  from  the  underlying  carotid  artery.  He  has  come  to  this  con- 
clusion because  he  has  not  found  it  in  tracings  of  the  liver  pulse  in 
cases  of  incompetent  tricuspid  valves.  There  is  no  doubt,  however, 
that  the  elevation  can  be  seen  on  tracings  from  the  inferior  vena  cava. 
The  explanation  of  its  absence  from  liver  tracings  is  probably  to  be 
ascribed  to  the  fact  that  the  great  mass  of  the  liver  substance  is  unable 
to  transmit  the  very  rapid  oscillation  of  pressure  due  to  the  closure  of 
the  auriculo-ventricular  valves.     These  venous  pulsations  are  much 


ac 

V 


Jug.V. 
Rod.  art. 


Fig,  421.     Venous  pulse-traciug  from  jugular  vein  compared  \\itli  the 
arterial  puLse-tracing  from  the  radial  artery. 

more  marked  in  cases  of  heart  disease,  where  there  is  partial  failure 
of  the  heart  pump  and  overfilling  of  the  venous  system,  often  combined 
with  incompetency  of  the  auriculo-ventricular  valves. 

Besides  the  favourable  influences  exercised  on  the  circulation 
through  the  veins  by  the  aspiration  of  the  thorax  and  the  momentary 
aspiration  of  the  heart-beat  itself,  a  considerable  part  is  played  in 
the  venous  circulation  by  the  contraction  of  the  muscles  of  the  body 
as  well  as  by  the  passive  movements  of  different  parts.  The  adjuvant 
effect  of  passive  or  active  movement  on  the  circulation  through  the 
veins  is  rendered  possible  by  the  existence  in  these  vessels  of  valves, 
which  are  semilunar  folds  of  the  intima  projecting  into  their  lumen, 
and  so  arranged  that  they  allow  the  passage  of  blood  only  towards  the 
heart.  Two  such  valves  are  as  a  rule  situated  opposite  to  each  other. 
Every  movement  of  a  limb,  active  or  passive,  causes  an  external 
pressure  on  the  veins,  and  therefore  empties  them  towards  the  heart. 
Thus,  in  walking,  each  time  the  thigh  is  moved  backwards  the  femoral 
vein  becomes  empty  and  collapses,  and  fills  again  as  soon  as  the  leg 
is  brought  forward  to  its  former  position  or  is  flexed  in  front  of  the 
body.  "When  muscular  movements  become  general,  as  in  walking  or 
running,  the  active  compression  of  the  veins  thus  brought  about 
plays  an  important   part  in  hurrying  the  blood  into  the  right  heart, 


1052  PHYSIOLOGY 

so  that  the  output  of  this  organ  is  increased  and  the  arterial  blood 
pressure  is  raised. 

Since  the  blood  in  the  vessels  is  subject  to  the  influence  of  gravity, 
we  should  expect  to  find  that  the  pressure  in  the  veins  of  the  foot  was 
equal  to  the  pressure  in  the  veins,  say,  of  the  hand  at  the  level  of  the 
heart  plus  the  pressure  equivalent  to  the  column  of  blood  between 
these  veins  and  the  heart,  i.e.  about  a  metre  of  blood.  On  measuring 
the  pressure  by  von  Recklinghausen's  or  by  Hill's  method  in  these 
veins,  this  is  not  found  to  be  the  case.  The  pressure,  indeed,  in  the 
veins  of  the  foot  is  but  little  higher  than  that  in  the  veins  of  the  hand. 
Von  Recklinghausen  found  that  after  subtracting  the  distance  between 
the  foot  and  the  heart  the  pressure  in  the  veins  was  negative  by  as 
much  as  40  cm.  In  the  same  way,  as  Hill  has  shown,  the  pressure  in 
the  capillaries  of  the  foot  is  about  the  same  as  in  the  capillaries  of  the 
hand.  When  a  man  assumes  the  upright  position  the  arteries  of  the  leg 
and  foot  contract  until,  under  the  combined  influence  of  the  heart's 
contraction  and  gravity,  the  blood-supply  to  the  capillaries  is  only 
sufficient  to  keep  the  pressure  in  these  vessels  at  a  certain  moderate 
height.  The  return  of  the  blood  from  the  dependent  parts  cannot  be 
ascribed  to  the  heart-beat  at  all,  but  is  due  to  the  extrinsic  mechanism 
of  circulation  through  the  veins,  i.e.  the  contractions  of  the  muscles  of 
the  Hmb  which  press  all  the  deep  and  superficial  veins,  and  in  virtue  of 
the  valves  force  the  blood  contained  therein  by  Poupart's  ligament 
into  the  abdomen.  The  fact  that  circulation  through  the  legs  is  de- 
pendent on  the  contractions  of  their  muscles  explains  why  it  is  so 
difficult  to  stand  still  for  any  length  of  time  without  moving,  and 
emphasises  the  need  of  moderate  exercise  for  the  maintenance  of  a 
normal  circulation. 


SECTION  VII 

THE  PULMONARY  CIRCULATION 

In  the  lungs  there  is  an  extensive  system  of  wide  capillaries  pre- 
senting very  little  resistance  to  the  flow  of  blood.  The  arterioles  are 
wide  and  have  only  a  slight  amount  of  muscular  fibre  in  their  walls, 
so  that  a  slight  pressure  sufl&ces  to  drive  the  blood  from  the  right 
to  the  left  heart.  The  determination  of  the  normal  average  pressure 
in  the  pulmonary  artery  presents  considerable  difficulties,  but  it 
probably  does  not  exceed  15  to  20  mm.  Hg.,  i.e.  about  one-sixth  of 
the  mean  aortic  pressure. 

The  capillaries  of  the  lungs  may  vary  passively  in  size  according 
to  the  condition  under  which  they  may  be  placed.  Thus,  whereas  at 
the  height  of  inspiration  the  blood  contained  in  the  lungs  is  about 
one-twelfth  of  the  whole  blood  in  the  body,  this  amount  is  diminished 
during  expiration  to  between  one-fifteenth  and  one-eighteenth,  and 
by  forcible  artificial  inflation  of  the  lungs  may  be  lessened  to  one- 
sixtieth.  These  changes  exercise  a  considerable  effect  on  the  sys- 
temic blood  pressure  and  are  largely  responsible  for  the  respiratory 
variations  observed  in  the  systemic  blood  pressure.  On  the  other 
hand,  the  distensibility  of  the  lung  capillaries  may  play  an  impor- 
tant part  in  enabling  the  lungs  to  act,  so  to  speak,  as  a  reservoir 
for  the  left  side  of  the  heart.  If,  in  consequence  of  raised  arterial 
pressure  or  other  factor,  there  is  a  temporary  excess  of  output  on 
the  right  side  that  cannot  be  dealt  with  at  once  by  the  left  heart, 
the  excess  is  taken  up  for  a  time  in  the  lung  capillaries. 

Vaso-motor  fibres  to  the  lung- vessels  have  been  described  as  running 
in  the  anterior  roots  of  the  third,  fourth,  and  fifth  dorsal  nerves. 
Their  action  is,  however,  of  little  importance,  and  their  very  existence 
is  doubtful.  Brodie  and  Dixon  obtained  no  vaso-constriction  in  the 
lungs  on  injection  of  adrenalin,  a  drug  which  causes  excitation  of  the 
sympathetic  vaso-constrictor  fibres  in  all  other  parts  of  the  body. 

If  we  examine  a  tracing  of  the  arterial  blood  pressure,  we  notice 
that  it  presents  certain  periodic  oscillations  which  accompany  the 
movements  of  respiration.  With  each  inspiration  the  blood  pressure 
rises  ;  with  each  expiration  it  falls.  The  synchronism  of  the  rise  and 
fall  with  the  respiratory  movements  is  not  exact,  since  the  rise  con- 
tinues for  a  short  time  after  the  beginning  of  expiration  before  it 

1053 


1054 


PHYSIOLOGY 


Alienal 
Bloodprei 


\ 


Expiradon 


Inspuativn 


begins  to  fall,  and  the  fall  continues  right  into  the  beginning  of  the 
next  inspiration,  so  that  the  highest  point  of  the  curve  occurs  at  the 
beginning  of  expiration  and  the  lowest  point  at  the  beginning  of 
inspiration.  During  the  fall  which  accompanies  expiration  the  heart- 
beats, as  shown  in  the  diagram  (Fig.  422),  become  less  frequent,  and 
an  obvious  explanation  of  the  fall  of  pressure  would  be  to  ascribe  it 
to  a  reflex  inhibition  of  the  heart.  On  dividing  both  vagi,  this  difference 
in  the  pulse-rate  during  inspiration  and  expiration  disappears,  but  the 
main  features  of  the  blood-pressure  curve  remain  the  same  ;  so  that 
we  must  look  for  some  mechanical  explanation  of  the  respiratory- 
undulations. 

We  have  already  seen  that  imder  normal  conditions  the  lungs  are 

in  a  state  of  over-distension, 
yV  k^     and  that  in  consequence  of 

this  condition  they  are  con- 
stantly tending  to  collapse, 
and  are  therefore  exerting  a 
pull  on  the  chest  wall.  As 
soon  as  we  admit  air  into  the 
pleural  cavity  by  perforating 
the  chest  wall  the  lungs 
collapse.  The  force  with  which 
the  lungs  tend  to  collapse 
amounts  to  6  mm.  Hg.  at  the 
end  of  a  quiet  expiration,  so  we  say  that  in  the  pleural  cavity  there  is 
normally  a  negative  pressure  of  6  mm.  Hg.  As  the  chest  expands  in 
inspiration  it  drags  the  lungs  still  more  open.  As  these  become  more 
distended  their  pull  on  the  chest  wall  becomes  greater,  and  hence  the 
negative  pressure  in  the  pleura  may  be  increased  during  forcible  in- 
spiration to  30  mm.  Hg.  It  must  be  remembered  that  the  heart  and 
great  veins  and  arteries  are  in  the  thorax  separated  from  the  pleural 
cavity  only  by  a  thin  yielding  membrane,  so  that  they  are  practically 
exposed  to  any  pressure,  positive  or  negative,  which  may  exist  in  the 
pleural  cavity.  Hence  even  at  the  end  of  expiration  the  heart  and  large 
vessels  are  subjected  to  a  negative  pressure  of  6  mm.  Hg.  Outside  the 
thorax  all  the  vessels  are  exposed  to  a  positive  pressure,  conditioned 
in  the  neck  by  the  elasticity  of  the  tissues  and  in  the  abdomen  by  the 
contractions  of  the  diaphragm  and  abdominal  muscles. 

Blood,  like  any  other  fluid,  will  always  flow  from  a  point  of 
higher  to  a  point  of  lower  pressure.  There  must  thus  be  a  constant 
aspiration  of  blood  from  peripheral  parts  into  the  thorax.  This  aspi- 
ratory  force  will  not  influence  arteries  and  veins  alike.  The  arteries, 
having  thick,  comparatively  non-distensible  walls,  will  be  very  little 
affected  by  the  negative  pressure  obtaining  in  the  thoracic  cavity. 


RespiraUin/ traci/ig. 

Fig.  422.  Diagram  of  blood-pressure  curve, 
showing  effects  of  the  respiratory  movements 
on  blood  pressure  and  pulse-rate.  (The  effects 
are  purposely  exaggerated.) 


THE  PULMONARY  CIRCrLATION  1050 

whereas  the  thin-walled  distensible  veins  will  be  largely  influenced 
by  the  same  factor.  The  total  result  then  of  the  negative  pressure  in 
the  pleural  cavities  is  to  increase  the  flow  of  blood  from  the  veins  into 
the  heart  without  affecting  to  any  appreciable  degree  the  outflow  of 
blood  from  the  heart  into  the  arteries.  The  more  pronounced  the 
negative  pressure  in  the  thorax,  the  greater  will  be  the  amount  of 
blood  sucked  into  the  heart  from  the  veins.  During  inspiration  there- 
fore the  heart  will  be  better  supplied  with  blood  than  during  expira- 
tion, and  this  factor  in  itself  will  tend  to  raise  the  arterial  blood  pressure. 
The  inspiratory  descent  of  the  diaphragm  will  moreover  tend  to 
increase  the  inflow  into  the  heart  by  raising  the  positive  pressure  in 
the  abdomen,  so  that  blood  is  pressed  out  of  the  abdominal  veins  and 
sucked  into  the  heart  and  the  thoracic  veins. 

Still  more  important  is  the  influence  of  the  respiratory  movements 
on  the  circulation  through  the  lungs.  In  trying  to  understand  this 
influence  it  must  be  remembered  that  the  pulmonary  capillaries  lie 
in  a  certain  amount  of  elastic  and  connective  tissue  and  are  separated, 
on  the  one  side  by  the  alveolar  epithelium  from  air  at  the  ordinary 
atmospheric  pressure,  and  on  the  other  by  the  pleural  endothelium 
from  the  pleural  cavity,  where  the  pressure  varies  from  6  to  30  mm. 
Hg.  below  the  atmospheric  pressure.  We  may  therefore  consider  the 
pulmonary  capillaries  as  lying  between,  and  attached  to,  two  concen- 
tric elastic  bags.  Under  normal  conditions,  since  these  bags  are  always 
tending  to  collapse,  the  inner  one  must  be  pulling  away  from  the  outer 
one,  and  the  outer  one  from  the  chest  wall.  Hence  there  must  be  a 
negative  pressure  in  the  tissues  between  these  two  bags — a  negative 
pressure  which  in  the  expiratory  condition  will  be  something  between 
0  and  —  6  mm.  Hg.,  and  in  the  inspiratory  condition  between  0  and 
—  30  mm.  Hg.  If  we  regard  the  average  pressure  within  the  pulmonarv 
capillaries  as  constant,  these  capillaries  must  be  more  dilated  in  the 
inspiratory  than  in  the  expiratory  condition.  This  dilatation  of  the 
pulmonary  capillaries  will  have  two  effects.  Their  capacity  will 
be  increased  and  the  resistance  they  present  to  the  flow  of  blood 
will  be  diminished. 

Let  us  now  consider  what  effect  these  changes  will  have  on  the 
general  arterial  blood  pressure.  We  will  assume  that  during  expiration 
the  pulmonary  vessels  have  a  capacity  of  25  c.c.  and  that  the  beat  of 
the  right  heart  is  forcing  through  them  10  c.c.  of  blood  per  second.  So 
long  as  the  chest  remains  in  the  expiratory  condition  10  c.c.  of  blood 
will  be  flowing  into  the  left  heart  and  into  the  aorta,  so  that  the  systemic 
blood  pressure  will  remain  constant.  Now  let  us  suppose  that  an 
inspiratory  enlargement  of  the  thorax  takes  jilace.  the  negative  pre.'^sure 
in  the  pleura  is  increased,  the  two  walls  of  the  lungs  are  pulled  farther 
away  from  one  another,  and  there  is  a  general  enlargement  of  the 


1056  PHYSIOLOGY 

pulmonary  capillaries.  We  will  assume  that  this  enlargement  increases 
the  capacity  of  the  pulmonary  capillaries  from  25  to  30  c.c.  Owing 
to  this  increased  capacity,  the  first  5  c.c.  of  blood  which  flows  into  the 
lungs  after  the  beginning  of  inspiration  will  not  flow  out  through  the 
pulmonary  vein,  but  will  simply  serve  to  bring  the  capillaries  into 
the  same  state  of  distension  as  before.  Hence  at  the  beginning  of  inspira- 
tion the  flow  through  the  pulmonary  vein  will  be  diminished  ;  there 
will  be  less  blood  discharged  into  the  left  heart,  and  therefore  a  fall 
in  systemic  pressure.  As  soon,  however,  as  the  increased  capacity 
of  the  pulmonary  vessels  is  made  up,  the  dilating  effect  of  the  inspira- 
tory movement  of  these  vessels  will  aid  the  flow  through  the  lungs, 
in  consequence  of  the  diminution  of  resistance,  so  that  the  same  force 
of  the  right  heart  which  drove  10  c.c.  of  blood  per  second  through  the 
former  resistance  during  expiration  will  now  drive  more,  say  12  c.c. 
of  blood.  There  is  thus  more  blood  entering  the  left  heart,  and  therefore 
a  rise  of  systemic  pressure  during  the  last  three-quarters  of  the  inspira- 
tory movement.  Expiration  will  have  exactly  the  reverse  effect.  At  the 
beginning  of  expiration  there  is  a  diminution  of  capacity  in  the  pulmo- 
nary vessels  from  30  to  25  c.c.  Hence  during  the  first  second  of  expira- 
tion the  outflow  of  blood  from  the  pulmonary  vein  into  the  left  heart 
will  be  17  c.c.  (12  c.c.  -f  5  c.c).  After  this,  the  increased  resistance  in 
the  pulmonary  capillaries  in  consequence  of  their  constriction  will  come 
into  play,  and  the  flow  of  blood  through  them  will  fall  once  more  from 
12  c.c.  to  10  c.c.  Hence  at  the  beginning  of  expiration  the  inflow  of 
blood  from  the  pulmonary  vein  into  the  left  heart  is  greater  than  at 
any  period.  The  arterial  pressure  will  therefore  rise  to  its  greatest 
height  at  the  beginning  of  expiration,  and  will  fall  during  the  last 
three-quarters  of  expiration,  but  will  attain  its  minimum  only  at  the 
beginning  of  the  next  inspiration. 

In  this  way  the  effect  of  the  respiratory  movements  on  the  systemic 
blood  pressure  can  be  entirely  explained  by  the  influence  they  exert 
on  the  lung- vessels  or  lesser  circulation.  On  the  other  hand,  Lewis 
regards  the  pericardial  pressure,  i.e.  the  direct  influence  of  the  thoracic 
movements  on  the  heart,  as  playing  a  much  more  important  part  than 
changes  in  the  pulmonary  circulation  in  the  production  of  the  respira- 
tory undulations  in  the  blood  pressure.  He  shows  moreover  that  in 
man  the  effect  of  respiration  on  arterial  blood  pressure  may  vary 
according  to  the  type  of  respiratory  movement,  a  deep  intercostal 
inspiration  (not  prolonged)  causing  a  pure  fall  of  pressure,  while  a 
deep  diaphragmatic  inspiration  gives  a  pure  rise  of  blood  pressure. 
In  expiration  the  reverse  effects  hold.  He  concludes  that  it  is  not 
possible  to  make  any  general  statement  as  to  the  nature  of  the  blood- 
pressure  response  to  a  particular  respiratory  act, 


SECTION   VIII 

THE  CAUSATION  OF  THE  HEART-BEAT 

If  the  heart  be  cut  out  of  the  body  of  a  cold-blooded  animal,  such  as 
the  frog  or  tortoise,  it  will  continue  to  beat  with  the  normal  sequence 
of  its  different  chambers  for  hours,  or  even  days,  provided  that  it  be 
kept  cool  and  moist.  In  the  case  of  a  warm-blooded  animal  the  heart 
is  similarly  capable  of  continuing  its  rhythmic  contractions  for  some 
little  time  after  excision.  The  period  of  survival  of  the  heart  is  less 
in  warm-blooded  than  in  cold-blooded  animals.  The  fact  that  in  both 
cases  the  heart  will  continue  to  beat  after  removal  from  all  its  con- 
nections with  the  central  nervous  system,  and  when  blood  is  no  longer 
flowing  through  it,  shows  that  the  causation  of  the  heart-beat  is  to 
be  sought  in  the  walls  of  the  heart  itself. 

The  heart  wall  consists  of  a  muscular  tissue  resembling  in  many 
respects  voluntary  muscle  ;  like  this,  it  presents  longitudinal  and 
transverse  striations  ;  like  this,  it  is  capable  of  contracting  in  response 
to  direct  stimulation.  Normally  voluntary  muscle  only  contracts  in 
response  to  impulses  from  the  central  nervous  system.  When  Remak 
described  the  existence  of  collections  of  ganglion-cells  in  the  sinus 
venosus,  it  was  natural  that  physiologists  should  ascribe  to  these 
collections  of  nerve-cells  the  same  automatic  rhythmic  functions  that 
had  been  found  by  Flourens  and  others  to  be  associated  with  the  grey 
matter  of  the  medulla  oblongata  in  connection  with  the  maintenance 
of  the  respiratory  movements. 

ANATOMY  OF  THE   FROG'S  HEART 

The  hearts  of  the  frog  and  of  the  tortoif-e  have  figured  .--o  hugely  in  tho 
researches  on  the  causation  of  the  heart -beat  that  it  may  bo  profitable  to  mention 
briefly  tho  main  points  of  their  anatomy. 

The  frog's  heart  consists  of  the  sinus  venosus,  which  receives  the  anterior  and 
posterior  venae  cavae,  two  auricles,  one  ventricle,  and  the  bulbus  arteriosus, 
which  opens  into  the  two  aorta?.  The  venous  blood  from  the  body  flows  into  tho 
sinus  venosus  by  tho  three  venae  cavae,  and  thenee  into  tho  right  auricle,  while 
tho  left  a\iricle  receives  tho  blood  from  the  lungs.  Tlio  ventricle  thus  receives 
mixed  arterial  and  venous  blood,  the  arterial  blood  being  directed  by  tho  spiral 
valve  of  the  bulbus  aortae  so  as  to  flow  chiefly  towards  the  head. 

Tho  muscular  fibres  of  the  heart  are  less  liighly  developed  than  those  of  tho 
mammalian  heart.  Tliey  are  spindle-shaped,  and  only  dimly  cross-striated.  Tho 
cross-striation  becomes  more  distinctly  marked  as  wo  proceed  from  sinus  to 

1057  67 


1058 


PHYSIOLOGY 


ventricle,  the  sinus  muscle  fibre  representing  the  most  primitive  condition. 
There  is  complete  muscular  continuity  betAveen  all  the  cavities  of  the  heart. 
The  circiUar  rmg  of  muscle  at  the  junction  of  smus  with  auricles  and  of  auricles 
with  ventricles  presents  only  slight  traces  of  cross-striation. 

The  heart  is  well  supplied  with  nerve  fibres  and  ganglion-cells.  The  two  vagi 
enter  the  smus  venosus  and  branch  just  under  the  pericardium.  Here  they 
become  connected  with  a  collection  of  nerve-cells,  spoken  of  as  Remak's  ganglion. 
From  the  sinus,  the  two  vagi,  now  called  septal  nerves,  pass  down  in  the  inter- 
aiu-icular  septum,  one  in  front  and  the  other  behind.  Near  the  auriculo -ventri- 
cular groove  they  enter  two  collections  of  ganglion-cells,  called  Bidder's  ganglia. 
From  these  ganglia  non-mediillated  fibres  are  distributed  to  surrounding  parts 
of  the  auricle  and  to  the  whole  of  the  ventricle.  In  the  upper  thu-d  of  the  ventricle 
occur  scattered  ganglion-cells  attached  to  the  nerve  fibres.  These  are  quite 
absent  in  the  lower  half  or  two-thirds. 

In  the  tortoise  (Fig.  424)  the  two  auricles  are  bound  together  by  a  flat  band 
of  tissue,  which  serves  also  to  connect  the  sinus  with  the  ventricle.    The  septum 


Ventricle 


Fig.  *424.  Tortoise's  heart  (after 
Gaskell)  as  it  appears  when  sus- 
pended for  registering  the  auricu- 
lar and  ventricular  contractions. 
N,  nerve-trunk  with  fibres  con- 
necting Remak's  and  Bidder's 
ganglia  ;  COR.  V,  coronary  vein. 


Fig.  423.  Diagram  of  frog's  heart.  (After 
Cyon.) 
V,  ventricle;  R.  A,  l.  A,  right  and  left  auricles 
(atrium);  s.v,  sinus  venosus ;  p.v,  pulmonary 
veins  ;  l.v.c.s  andR.v.c.s,  left  and  right  su- 
perior vena  cava;  v. c.i,  vena  cava  inferior; 
Tr.A,  truncus  arteriosus. 


between  the  auricles  arises  from  the  central  Ime  of  this  junction  wall.  The  two 
vagi  nerves  pass  into  a  large  accumulation  of  ganglion-cells  in  the  sinus,  and 
thence  along  the  basal  wall  to  the  auricido-ventricular  groove  lying  just  under  the 
pericardium.  In  the  groove  they  pass  into  a  collection  of  ganglion-cells,  whence 
fibres  are  given  off  to  both  auricles  and  ventricle.  As  they  leave  the  sinus,  a 
branch  is  always  given  off  by  the  right  nerve  to  accompany  the  coronary  vein, 
which  conveys  blood  from  the  ventricular  wall  to  the  sinus.  Thus  the  nerves  of 
the  tortoise's  heart  are  altogether  more  accessible  than  those  of  the  frog's  heart. 
In  other  points  the  tortoise's  heart  is  similar  to  the  frog's  heart,  though  consider- 
ably larger. 

THE  AUTOMATIC  CONTRACTION  OF  THE  FROG'S  HEART 
The  frog's  heart  in  the  body,  or  when  removed  from  the  body- 
intact,  beats  regularly,  the  contraction  starting  in  the  sinus,  then 
travelling  to  auricles,  ventricle,  and  bulbus.  If,  however,  the  heart 
be  removed  by  cutting  it  across  the  sino-auricular  junction,  or  if  the 
auricles  be  functionally  separated  from  the  sinus  by  a  ligature  round 
this  junction  (Stannius's  ligature),  the  auricles  and  ventricle  stop  in 
an  uncontracted  condition  (diastole),  while  the  sinus  goes  on  beating 
regularly.  After  the  lapse  of  a  period  varying  from  five  minutes  to 
half  an  hour  the  detached  part  of  the  heart  begins  to  beat,  at  first 


THE  CAUSATION  OF  THE  HEART-BEAT  1059 

slowly  and  then  more  rapidly,  but  never  attaining  the  rate  of  the  sinus. 
The  auricles  beat  first,  and  then  the  ventricle.  If  now  the  ventricle 
be  cut  away  by  an  incision  in  the  auriculo-ventricular  groove  from 
the  auricles,  the  latter  go  on  beating  ;  while  the  former,  after  a  few 
beats  due  to  the  excitation  of  the  incision,  stops  still,  and  only  after  a 
considerable  time  may  begin  again  to  contract  very  slowly. 

On  the  other  hand,  a  ventricle-apex  preparation  (that  is  to  say,  the 
lower  two-thirds  of  the  ventricle  separated  functionally  from  the  rest 
of  the  heart)  never  beats  again  under  normal  circumstances.  To  single 
stimuh  it  responds  with  a  single  beat,  not  with  a  series  of  beats  as  the 
whole  heart  does.  If  the  lower  third  of  the  ventricle  be  separated  func- 
tionally in  the  living  frog  by  crushing  the  ring  of  tissue  between  it  and 
the  upper  third,  it  never  gives  a  spontaneous  beat  again,  although  it  is 
under  the  most  normal  conditions  possible  in  the  circumstances.  There 
is  thus  a  descending  scale  of  automatic  power  in  the  different  parts  of 
the  frog's  heart — from  the  sinus,  where  it  is  highest,  to  the  lower  pait 
of  the  ventricle,  where  it  is  apparently  absent.  From  this  fact  it  has 
been  thought  that  the  automaticity  of  the  frog's  heart  is  dependent  on 
the  ganglia  present  in  it.  The  contraction  was  supposed  to  be  started 
by  impulses  proceeding  from  the  sinus  ganglion.  If  this  were  cut  off. 
Bidder's  ganglia,  or  the  scattered  cells  in  the  upper  third  of  the  ven- 
tricle, could,  it  was  thought,  take  up  its  task  of  originating  impulses. 
The  muscle-cells  under  this  hypothesis  act  as  the  servants  of  the 
ganglion-cells,  just  as  the  voluntary  muscles  wait  on  the  commands  of 
the  cells  in  the  spinal  cord  and  brain. 

The  view  that  the  ganghon-cell  sends  out  rhythmic  impulses  had, 
however,  to  be  discarded  when  it  was  discovered  that  the  muscle 
forming  the  lower  third  of  the  ventricle  either  of  the  frog  or  the  tortoise, 
though  free  from  ganghon-cells,  could  be  excited  by  various  means  to 
rhythmic  contractions.  Thus  it  could  be  set  into  rhythmic  action 
when  supplied  with  salt  solution  under  pressure,  through  a  perfusion 
cannula,  or  when  excited  by  the  passage  of  a  constant  current  or  of 
weak  induction  shocks.  The  fact  that  the  heart  muscle  responded  to 
continuous  stimulation  by  a  rhythmic  discharge  suggested  that  the 
function  of  the  ganghon-cells  was  to  furnish  a  constant  stimulation  to 
the  muscle-cells  and  so  maintain  these  in  rh^-thmic  activity. 

The  theory  of  the  ganghonic  origin  of  the  cardiac  rh}-thm  was 
seriously  affected  by  a  series  of  researches  carried  out  by  Gaskell  and 
by  Engelmann.  The  arguments  against  the  '  neurogenic  '  hypothesis 
may  be  summarised  as  follows  : 

(a)  The  cardiac  muscle,  free  from  any  ganglion-cells  whatsoever, 
can  be  excited  by  various  means  to  rhythmic  contraction.  When,  in 
the  living  frog,  the  apex  of  the  ventricle  is  crushed  off  from  the  base 
so  as  to  leave  only  material  continuity  between  the  two  parts,  the 


1060 


PHYSIOLOGY 


circulation  of  the  blood  is  maintained  by  the  contraction  of  all  the 
parts  of  the  heart  except  the  apex,  which  never  resumes  its  activity. 
If,  however,  the  intraventricular  pressure  be  raised  by  clamping  the 
aorta  the  apex  begins  to  beat  at  its  own  rhythm,  which  is  independent 
of  the  rhythm  of  the  rest  of  the  heart.  Moreover  a  strip  can  be  cut 
from  the  apex  of  the  tortoise's  ventricle  (Fig.  425),  free  from  ganglion- 
cells,  which  on  keeping  in  a  moist  chamber  and  moistening  occasion- 
ally with  normal  salt  solution  enters  into  rhythmic  contractions. 

(b)  In  the  frog  it  is  possible  to  excise  the  inter-auricular  septum 
with  its  ganglia,  and  a  considerable  portion  of  the  ganglia  in  the  sinus 

venosus  and  at  the  base  of  the 
ventricles,  without  interfering 
in  any  way  with  the  cardiac 
rhythm.  This  experiment  is 
still  easier  to  carry  out  in  the 
tortoise's  heart,  where  the 
nerves  and  ganglia  run  in  the 
basal  portion  of  the  auricles. 
This  can  be  excised,  leaving 
the  two  auricular  appendages 
in  connection  with  the  sinus 
venosus  and  with  the  ven- 
tricles. 

(c)  The  heart  in  the  develop- 
ing chick  can  be  seen  beating 
at  a  time  when  it  is  quite  free 
from  nerve-cells,  which  only 
extend  into  it  at  a  later  date. 
{d)  Remak's  ganglia  are 
situated  at  the  point  where  the 
two  vagus  nerves  enter  the  heart,  and  under  the  microscope  can  be  seen 
to  be  connected  with  the  fibres  of  these  nerves.  We  have  now,  from  the 
discovery  of  Landley  and  Dickinson,  a  means  of  judging  of  the  action 
of  ganglion-cells  in  the  drug  nicotine,  which  first  stimulates  and  then 
paralyses  nerve-cells  themselves  or  the  synapses  between  the  cells  and 
the  nerve  fibres  in  connection  with  them.  Direct  application  of  nicotine 
to  the  heart,  after  a  primary  period  of  slowing,  leaves  the  heart-beat 
practically  unaltered,  the  normal  sequence  of  beat  in  the  various 
cavities  being  unaffected.  After  the  application  of  the  drug,  however, 
stimulation  of  the  trunk  of  the  vagus  is  without  effect,  though  slowing 
or  stoppage  of  the  heart  may  still  be  produced  by  excitation  of  the 
post  ganglionic  nerve  fibres  of  the  vagus  which  arise  from  the  cells  of 
Remak's  ganglia.  These  ganglia  must  therefore  be  regarded  not  as  a 
motor  centre  for  the  heart,  but  merely  as  a  distributing-centre  for  the 


Fig.  425.    Tortoise's  heart    from  dorsal  sitrfate. 

(Gaskell.) 

S,    sinus ;    J,    sino-auricular   junction ;     A, 

auricles  ;  C,  coronary  vein ;  V,  ventricle.    (The 

dotted  line  shows  how  a  strip  may  be  cut  from 

the  ventricle  apex.) 


THE  CAUSATION  OF  THE  HEART-BEAT 


1061 


inhibitory  fibres  of  the  vagus.  Since  tetanisation  of  the  heart  with  weak 
currents  also  causes  local  inhibition,  it  would  seem  that  the  finer  nerve 
fibres  ramifying  throughout  the  muscular  subitance  are,  to  a  large 
extent  at  all  even':s,  inhibitory  in  their  function.  This  is  confirmed  by 
the  fact  that  atropine,  which  paralyses  the  inhibitory  fibres  of  the  vagus, 
also  aboHshes  the  direct  inhibitory  effect  of  tetanisation  on  the  heait 
muscle.  Gaskell  and  Engelmann  therefore  came  to  the  conclusion  that 
the  source  of  the  cardiac  rhythm  was  to  be  found,  not  in  the  ganglia 
scattered  about  its  cavities,  but  in  the  muscular  cells  themselves. 

The  normal  sequence  of  events — i.e.  the  subordination  of  the 
ventricle  to  auricles  and  auri- 
cles to  sinus,  so  that  the  beat 
always  follows  in  the  order, 
sinus,  auricles,  ventricle,  bul- 
bus — can  be  ascribed  to  the 
variation  in  the  natural 
rhjrthm  of  these  different 
cavities.  It  is  possible  to 
record  the  contractionsof  each 
of  these  parts  of  the  heart 
separately,  after  having 
divided  them,  either  function- 
ally by  crushing  the  interven- 
ing tissue,  or  by  actual  section. 
Under  such  conditions  it  is 
found  that  there  is  a  descend- 
ing scale  of  rhythm  from  sinus 
to  bulbus,  the  contractions  of 

the  sinus  being  most  frequent,  those  of  the  ventricle  and  bulbus  the 
least  frequent.  Thus  it  is  impossible  for  the  ventricle  to  beat  at  its 
own  rhythm,  since  before  it  is  ready  to  beat  again  after  performing 
one  beat  it  receives  an  impulse  from  the  auricles  causing  an  excited 
biat.  That  the  normal  sequence  of  contractions  is  dependent  simply 
on  the  natural  rhythm  of  the  sinus  is  shown  by  the  fact  that  by 
exciting  the  ventricle  by  nieans  of  induction  shocks  repeated  at  a 
rhythm  slightly  greater  than  that  of  the  sinus  it  is  possible  to  excite 
a  reversed  rhythm,  the  order  of  the  beat  bsing  now  ventricle,  auricles, 
sinus  venosus. 

The  dependence  of  the  ventricular  rhythm  on  the  beat  of  the  sinus 
may  be  shown  by  a  simple  experiment.  The  ventricle  is  connected 
with  a  lever  suspended  by  a  spring  so  as  to  record  its  contractions  on 
a  drum.  A  platinum  loop  connected  with  a  galvanic  battery  is  put 
round  the  heart,  either  round  the  sinus  or  round  the  ventricle  (Fig.  ■42G). 
When   a  current  is  allowed  to    pass    through   the  inner  loop   the 


1062  PHYSIOLOGY 

corresponding  part  of  the  heart  is  warmed.  When  the  ventricle  alone 
is  warmed  the  beats  become  larger,  but  the  rhythm  is  unaltered.  On 
lowering  the  loop  so  as  to  warm  the  sinus,  the  rhythm  of  the  whole 
heart  is  quickened,  but  the  size  of  the  ventricular  beats  is  unaffected. 
The  different  rhythmic  power  of  these  parts  of  the  heart  is  appa- 
rently connected  with  the  histological  characters  of  the  muscle  fibres 
at  each  part.  The  lowly  difEerentiated  sinus  cell  has  well-marked 
rhythmic  power  and  a  quick  rhythm  of  beat,  but  is  not  able  to  exert 
such  force  in  its  contraction.  The  more  highly  difEerentiated  ventricle 
cell  has  only  a  slight  rhythmic  power,  but  beats  forcibly  and  is  a  good 
servant  of  the  sinus. 

THE  PROPAGATION  OF  THE  WAVE  OF  CONTRACTION 
The  normal  contraction  started  in  the  sinus  venosus  is  j^ropagated 
to  the  auricles,  thence  to  the  ventricle,  and  thence  to  the  bulbus 
aortae.  Between  the  contractions  of  each  of  these  cavities  there  is  a 
slight  pause,  whereas  the  contraction  spreads  so  rapidly  over  each 
cavity  that  all  parts,  say  of  the  auricles  or  ventricle,  appear  to  con- 
tract simultaneously.  It  is  obvious  that  the  excitatory  wave  might  be 
propagated  through  the  heart  from  one  muscle-cell  to  another,  or  by 
means  of  nerve  fibres,  which  would  excite  the  muscular  tissue  of  each 
cavity  to  contract. 

The  distinct  pause  which  intervenes  between  the  contractions  of 
auricles  and  ventricle  was  long  regarded  as  evidence  for  the  nervous 
character  of  the  contraction,  and  as  showing  the  operation  of  a  nerve- 
centre  in  the  co-ordination  of  the  contractions  of  different  cavities. 
A  contraction  wave  may,  however,  be  started  at  any  part  of  the  heart 
and  may  travel  from  this  to  all  other  parts.  Thus,  although  the  normal 
direction  of  the  contractions  is  from  sinus  to  ventricle,  it  is  possible, 
by  stimulating  the  apex  of  the  ventricle,  to  excite  contractions  in  the 
reverse  order,  viz.  from  ventricle  to  sinus.  Such  a  fact  is  at  variance 
with  all  our  present  knowledge  of  excitation  of  motor  nerves.  Excita- 
tion of  the  nerve  going  to  the  sartorius,  or  any  part  of  the  nerve,  may 
excite  contractions  of  all  the  fibres  of  which  the  muscle  is  composed. 
On  the  other  hand,  excitation  of  a  part  of  the  muscle  which  is  free  from 
nerve  fibres  causes  a  contraction  which  is  limited  to  the  muscle  fibres 
directly  excited  and  does  not  extend  to  the  nerves.  If  motor  nerves 
arose  from  the  hypothetical  motor  ganglion  of  the  heart  and  passed 
to  the  ventricular  muscle,  one  would  not  expect  that  contraction  of 
the  ventricular  muscle  could  excite  these  nerves  and  so  cause  the 
propagation  of  a  wave  of  contraction  in  the  reverse  direction. 

That  the  propagation  cannot  be  due  to  any  nerve-trunks  running 
from  sinus  to  ventricle  is  shown  by  various  experiments  of  Engelmann 
and  Gaskell.   Thus,  if  the  auricle  is  slit  up  by  a  series  of  interdigitating 


THE  CAUSATION  OF  THE  HEART-BEAT     1063 

cuts,  the  contraction  wave  starting  from  the  sinus  travels  along  the 
auricular  muscle  around  the  end  of  each  section,  and  finally,  on  arrival 
at  the  ventricle,  causes  a  contraction  of  this  cavity.  In  the  heart 
of  the  tortoise  the  nerve-trunks  run,  not  in  the  interauricular 
septum,  but  in  a  band  of  tissue  joining  the  sinus  to  the  ven- 
tricles ;  this  band  can  be  excised  with  all  its  contained  nerves 
without  interfering  in  any  way  with  the  normal  sequence  of  contrac- 
tions. Moreover  the  pause  observed  between  the  contractions  of 
auricles  and  ventricles  has  been  shown  by  Gaskell  to  be  due  to  the 
retardation  of   the  excitatory  wave  which  occurs  in  its  propagation 


Fia.  427.     Heart  of  tortoise  with  auricle  slit  up  so  as  to  cause  a  partial 
block.     (Gaskkll.) 

through  the  muscular  tissue  in  the  auriculo- ventricular  junction.  A 
similar  retardation  of  the  wave  can  be  produced  at  any  point  either 
in  auricles  or  ventricle  by  diminishing  the  conducting  muscular  tissue 
to  a  sufficiently  small  extent.  Thus,  if  the  auricle  of  the  tortoise  be 
divided  as  in  the  diagram  (Fig.  427),  it  will  be  noticed  that  the  sinus 
first  contracts,  then  the  auricular  half  As  ;  a  distinct  pause  then 
occurs  while  the  contractile  process  is  passing  over  the  '  bridge,'  and 
finally  Av  contracts,  followed  by  the  ventricle.  The  apparent  pause 
between  the  contraction  of  the  auricles  and  ventricle  is  due  therefore 
to  a  partial  '  block  '  at  the  auriculo-ventricular  junction.  If  the 
block  be  increased  in  the  experiment  just  quoted,  as,  for  instance, 
by  allowing  the  bridge  of  tissue  to  dry  or  by  making  it  still 
narrower,  it  may  be  found  that  only  one  out  of  every  two  con- 
tractions passes  across  the  bridge  (Fig.  428),  and  the  slighte.st 
increase  in  the  resistance  to  the  propagation  of  the  wave  may  lead  to 


1064 


PHYSIOLOGY 


the  block  becoming  complete.    On  moistening  the  bridge  again  every 
contraction .  may  be  seen  to  pass. 

By  the  methylene-blue  method  it  is  possible  to  demonstrate  a  close 
network  of  non-medullated  fibres  surromiding  all  the  muscle-cells  of 
the  heart.  It  is  obvious  that  the  experiment  just  quoted  would  not 
exclude  the  possibility  of  propagation  occurring  through  such  a  nerve 
network.  The  properties  of  the  network  would 
have  to  differ  from  those  of  any  of  the  nerve- 
tissues  with  which  we  are  acquainted  ;  whereas 
we  know  that  under  certain  circumstances  im- 
pulses may  be  transmitted  from  fibre  to  fibre 
even  in  striated  muscle,  and  such  a  mode  of  pro- 
pagation is  the  most  obvious  explanation  of  the 
phenomena  observed  in  the  heart. 

If  the  auricles  be  soaked  for  some  time  in 
distilled  water  they  enter  into  a  condition  of 
what  is  known  as  water-rigor  {Wasserstarre).  In 
this  condition  they  are  incapable  of  contracting, 
but  can  still  propagate  the  wave  from  sinus  to 
ventricle.  This  experiment  has  been  regarded 
as  a  demonstration  of  the  part  taken  by  nerve 
fibres  in  the  propagation  of  the  wave,  but  such  an  explanation  is  not 
necessary,  since  a  similar  condition  of  water-rigor  in  a  voluntary 
muscle  fibre  has  been  shown  to  allow  the  passage  of  an  excitatory 


Fig.  428.  Contraction 
of  auricles  and  ventri- 
cles of  tortoise  heart. 
The  auriciilo -ventricu- 
lar groove  has  been 
clamped  so  as  to  pro- 
duce a  partial  block 
allowing  only  every 
second  contraction  to 
pass.    (Gaskell.) 


OS  mnc      In  [3 

Fig.  429.     Heart  of  Limulus  from  dorsal  surface.     (Carlson.) 
mnc,  median  nerve-cord  ;  In,  lateral  nerve-trunks. 

wave  through  the  affected  part  to  the  normal  portion  of  the  muscle, 
which  then  responds  by  a  contraction. 

A  series  of  interesting  researches  by  Carlson  on  the  mechanism  of  the  heart- 
beat in  the  kmg-crab  Limulus  have  been  thought  to  throw  light  on  the  vexed 
question  of  the  automatism  of  the  vertebrate  heart. 

In  Limulus  the  heart  forms  a  segmented  tube  of  ordinary  striated  muscular 
fibres.  In  large  specimens  the  tube  may  be  from  10  to  15  cm.  long  and  2  to 
2^  cm.  broad.  Like  the  hearts  of  most  other  invertebrates  and  of  all  vertebrates, 
it  has  a  local  system  of  ganglion-cells,  but  so  situated  that  they  can  be  cut  away 
entirely  from  the  muscular  portions  of  the  organ.  The  arrangement  of  the  cardiac 
nervous  system  in  Limulus  is  sho\vn  in  Fig.  429. 

The  ganglion-colls  arc  collected  chiefly  in  a  dorsal  nerve  ganglion  cord  which 
runs  almost  the  Avhole  length  of  the  heart.  From  this  cord  non-medullated  nerve 
fibres  pass  directly  into  the  substance  of  the  heart,  and  also  send  branches  to 


THE  CAUSATION  OF  THE  HEART-BEAT  1065 

two  lateral  ncrve-lriinks,  by  wliich  Hhrva  arc  distributed  to  all  parts  of  the 
heart. 

The  heart  normally  contracts  about  forty  times  per  minute.  Each  contrac- 
tion affects  all  parts  practically  simultaneously,  tliough  in  the  djing  heart  the 
posterior  portions  apparently  contract  slightly  before  the  anterior,  and  may 
continue  to  contract  after  the  anterior  end  has  come  to  a  standstill. 

Division  of  the  muscular  tissue  leaving  the  nerve-strands  intact  does  not 
alter  in  any  way  the  synchronism  of  contraction  of  the  two  ends  of  the  heart. 
Division  of  the  nervous  cord  into  two  parts,  the  section  being  carried  between 
the  posterior  third  and  anterior  two-thirds,  causes  complete  lack  of  co-ordination 
between  the  two  ends  ;  both  ends  of  the  heart  continue  to  contract,  but  at 
different  rhythms.  Extirpation  of  the  nerve-cord  abolishes  spontaneous  contrac- 
tions. If  the  anterior  half  of  the  dorsal  ganglionic  cord  be  excised,  all  parts  of  the 
heart  will  continue  to  contract  in  unison.  If  now  the  lateral  nerve-trunks  be 
divided,  the  anterior  half  of  the  heart  ceases  to  contract,  showing  that  it  was 


Fig.  430.  '  Nerve-muscle  preparation '  of  heart  of  Limulus  consisting  of 
the  muscle  of  the  two  anterior  segments,  with  the  two  lateral  nerves. 
(Carlson.) 

being  excited  by  impulses  arising  in  the  posterior  part  of  the  ganglionic  cord. 
It  is  possible  therefore  to  make  a  nerve-muscle  preparation  of  the  anterior 
jiart  of  the  heart,  consisting  of  the  miLscle  of  the  first  two  segments  \v1th  a  longer 
stretch  of  the  lateral  nerves  (Fig,  430),  Stimidation  of  the  lateral  nerves  with 
a  single  shock  caiLses  a  single  beat  of  the  anterior  segments  ;  tetanising  shocks 
cause  a  continued  contraction  of  the  muscle  preparation. 

There  seems  to  be  no  doubt  that  in  this  animal  the  beat  of  the  heart  is  origi- 
nated and  co-ordinated  by  the  action  of  the  local  ganglionic  centres.  Moreover 
Carlson  has  shoAvn  that  the  inhibitory  nerve  to  the  heart  acts,  not  by  direct 
influence  on  the  muscle  fibres,  but  by  an  inhibition  of  the  automatic  activity 
of  the  ganglionic  cells,  thus  confirming  for  this  special  case  the  general  view 
of  inhibition  long  ago  put  forward  by  Morat,  but  not  now  generally  accepted. 

The  heart  muscle  does  not  show  a  refractory  period,  but  on  direct  stimulation 
with  repeated  shocks  there  may  be  a  summation  of  contractions,  which  may 
fuse  to  a  complete  tetanus.  The  question  naturally  arises  how  far  the  heart  of 
Limulus  is  to  be  regarded  as  a  special  case,  or  how  far  we  may  transfer  results 
gained  from  experience  on  this  heart  to  those  of  other  hearts  in  which  a  perfect 
separation  betwet-n  ganglion-cells  and  muscle  fibres  is  not  so  easily  attainable. 
Carlson  has  sought  to  show  the  applicability  of  his  results  to  the  explanation 
of  the  cardiac  mechanism  in  vertebrates  by  a  series  of  observations  on  other 
invertebrates'  hearts,  where  the  nmscular  and  nervous  tissues  are  not  so  easily 
dissociable.  Such  hearts  present  phenomena  very  analogous  to  those  of  the 
frog's  heart.  According  to  him  the  phenomenon  of  the  refractory  period,  the  '  all 
or  none  '  law  of  contraction,  and  the  absence  of  tetanus  in  the  heart  of  the  frog  is 
due,  not  to  the  peculiar  functions  of  the  muscle  fibres,  but  to  the  fact  that  in  all 
our  experiments  we  are  affecting  muscular  and  nervous  tissues  simultaneoiLsly. 


1066  PHYSIOLOGY 

In  the  absence  of  more  perfect  knowledge  of  the  properties  of  the  nerve-nets 
Avhich  siuTomid  involuntary  and  cardiac  muscle  fibres  a  decision  of  the  point 
is  not  yet  possible.  The  muscle  and  nerve  fibres  of  Limiilus  show,  however, 
important  difl^erences  from  the  cardiac  muscle  of  the  frog  in  their  reaction  to 
chemical  stimuli.  Acceptation  of  the  neurogenic  theory  would  necessitate  the 
predication  of  a  type  of  nervous  tissue  endowed  with  properties  for  which  we 
have  no  analogy  in  any  of  the  nerve  tissues  which  have  been  the  subject  of  exact 
investigation,  whereas  the  myogenic  theory  only  ascribes  to  the  muscle-cells  of 
the  heart  properties  which  are  the  common  attribute  of  all  protoplasm,  or  are  dis- 
played in  a  less  marked  degree  by  the  ordinary  skeletal  muscle  fibres.  It  would, 
at  any  rate,  be  prematm"e  to  transfer  unreservedly  all  the  results  obtained  on  the 
heart  of  the  Limulus,  the  muscle  fibres  of  which  have  the  structiu'e  and  behavioiu" 
of  skeletal  muscle  fibres,  to  the  explanation  of  the  phenomena  exhibited  by  the 
hearts  of  vertebrates. 

THE  HEART-BEAT  AS  A  WAVE  OF  CONTRACTION 
If  the  beat  of  the  frog's  ventricle,  or  a  strip  of  mammalian  ventricle, 
be  recorded,  the  curve  obtained  resembles  closely  the  twitch  of  a 
voluntary  muscle  produced  in  response  to  a  single  excitation.  Whereas, 
however,  a  single  contraction  with  the  subsequent  relaxation  of 
voluntary  muscle  only  lasts  about  one-tenth  of  a  second,  the  contrac- 
tion of  the  mammalian  ventricular  muscle  lasts  three-tenths  to  four- 
tenths  of  a  second,  of  the  frog's  ventricle  about  half  a  second,  and  of 
the  tortoise  ventricle  about  two  seconds.  In  the  heart,  as  in  a  volun- 
tary muscle  fibre,  the  contracting  power  process  originates  at  the 
stimulated  point  and  travels  thence  to  all  other  points. 

The  progress  of  the  excitatory  wave  is  well  seen  if  a  record  be  taken 
of  the  electrical  changes  resulting  in  the  heart  from  a  single  stimula- 
tion. If  the  two  ends  of  a  strip  of  ventricular  muscle  be  connected 
with  the  two  terminals  of  a  capillary  electrometer,  stimulation  at 
one  end  causes  a  diphasic  variation,  showing  that  the  excitatory 
process  starts  at  the  stmiulated  end  and  travels  to  the  other  end 
of  the  heart.  Thus  if  the  acid  of  the  electrometer  be  connected 
with  the  base  of  the  ventricle  and  the  mercury  of  the  capillary  be 
connected  with  the  apex,  stimulation  at  the  base  causes  a  wave 
passing  from  bage  to  apex.  Directly  after  the  stimulation  therefore 
the  base  becomes  negative  and  the  column  of  mercury  moves  towards 
the  acid  ;  a  moment  later  the  contraction  extends  to  the  apex.  All 
parts  of  the  heart  are  now  in  a  similar  condition  of  excitation  :  there 
is  no  difference  of  potential  between  the  two  terminals  and  the  mercury 
comes  back  quickly  to  the  base  line.  Relaxation,  like  contraction, 
starts  first  at  the  base  and  proceeds  thence  to  the  apex.  There  is  thus 
a  small  period  during  which  the  apex  is  still  contracted  while  the 
base  is  relaxed  and  the  apex  is  therefore  negative  to  the  base.  This 
terminal  negativity  of  the  apex  is  shown  on  the  capillary  electrometer 
by  the  excursion  of  the  column  of  mercury  away  from  the  point  of 
the  capillary  (cp.  Fig.  88,  p.  259). 


THE  CAUSATION  OF  THE  HEART-BEAT 


1067 


Analogous  effects  are  obtained  on  leading  off  the  spontaneously 
beating  heart  in  the  frog  or  tortoise  (Fig.  431).  The  conditions  are, 
however,  rather  more  complex,  and  the  most  usual  variation,  as  Gotch 
has  shown,  is  triphasic.  This  is  probably  due  to  the  fact  that  the  wave 
of  excitation  follows  the  original  arrangement  of  the  muscular  fibres. 
In  its  most  primitive  form  the  vertebrate  heart  is  composed  of  a 
simple  tube  in  which  a  contraction  starts  at  the  venous  end  and  is 
propagated  in  a  wave-like  manner  along  the  tube  to  the  arterial  end. 
In  the  higher  vertebrates  the  heart  at  its  fir.st  appearance  has  the 


Fig.  431.     Electrometer  record  of  variation  of  spontaneously  beating  frog's 
heart.     (Gotch.) 


same  tubular  form,  but  the  simple  tube  very  rapidly  becomes  modified, 
partly  by  twisting  on  itself,  partly  by  the  outgrowth  of  the  dorsal 
or  the  ventral  wall  of  the  tube  to  form  the  cavities  of  the  auricle  and 
ventricle.  In  the  frog  it  is  easy  to  obtain  direct  records  of  the  con- 
tractions of  the  different  cavities,  showing  the  regular  sequence 
through  sinus,  auricle,  ventricle,  and  bulbus.  The  tube  is,  how- 
ever, twisted  on  itself  to  form  the  ventricle,  hence  the  part  of  the 
ventricle  in  muscular  continuity  with  the  auricles  is  genetically 
posterior  to  that  part  of  the  ventricle  which  immediately  adjoins  the 
bulbus.  Hence  it  comes  about  that  in  the  frog's  ventricle  the  wave 
of  electrical  change  which  accompanies  the  excitatory  condition  is 
triphasic.  The  excitatory  process  in  the  auricles  is  succeeded 
immediately  by  activity  of  the  base  of  the  ventricle.  The  wave  then 
travels  to  the  apex,  and  from  here  back  to  the  base  in  the  neighbour- 
hood of  the  bulbus,  so  that  the  base,  as  judged  by  leading  off  to  the 


1068 


PHYSIOLOGY 


galvanometer  or  electrometer,  becomes  negative  twice  in  the  course 
of  the  cardiac  contraction. 

We  must  conclude  therefore  that  the  ventricular  systole  is  com- 
parable with  a  simple  muscular  twitch  and  cannot  be  regarded  as 
the  summation  of  several  contractions.  Since  the  excitatory  process 
extends  in  the  form  of  a  wave  not  only  to  all  parts  of  the  same  cavity 
but  to  all  parts  of  the  heart,  it  is  evident  that  the  musculature  of  the 

heart  is  to  be  compared,  not 
^X  with   skeletal    muscle    com- 

posed of  many  fibres,  but  to 
a  single  muscle  fibre  in  which 
all  parts  are  in  functional 
continuity. 

THE     BEAT    OF    THE 
MAMMALIAN   HEART 

The  mammalian  heart,  like 

the    heart    of    cold-blooded 

animals,  will  beat  for  some 

time  after  it  has  been  cut  out 

of  the  body,  and  a  perfectly 

rhythmic    activity    may    be 

maintained     for    hours     by 

feeding    the  heart  from  the 

coronary  arteries  either  with 

defibrinated   blood   or   with 

oxygenated  Ringer's  solution, 

with  or  without  the  addition 

of  j?lucose 
Fig.  432.      Distribution  of  potential  differences  n         i' 

due    to    electrical    variations   in  the    beating  OrangllOn-Cells    are    tound 

heart.    (Waller.)  jj^    ^j^^    mammalian     heart 

To  record  the  variations  any  of  the  points  i    .1  •  j-    ,1 

a  may    be   led  off,  together  with  any  of  the    around   the   opeumgS  ot    the 

P^'^ts  b.  great  veins,  along  the  border 

of  the  interauricular  septum, 
in  the  groove  between  auricles  and  ventricles,  and  in  the  uppermost 
parts  of  the  ventricles. 

The  ventricles  of  mammals  are  endowed  with  a  greater  rhythmic 
power  than  the  corresponding  cavities  in  the  frog  and  tortoise.  It  is 
possible  to  sever  or  crush  all  the  nervous  and  muscular  connections 
between  auricles  and  ventricles  without  destroying  their  mechanical 
connection  by  means  of  fibrous  tissue.  Such  a  procedure  does  not, 
even  for  a  moment,  stop  the  contractions  of  the  ventricles,  which  go 
on  beating  at  a  rhythm  which  is  independent  of  and  slower  than  that 
of  the  auricles.     Porter  has  shown  that  a  mere  fragment  of  the  ventri- 


THE  CAUSATION  OF  THE  HEART-BEAT  1009 

cular  wall,  perfectly  free  from  ganglion-cells,  may  maintain  rhythmic 
contractions  for  some  hours  if  fed  by  an  artificial  circulation  through 
a  branch  of  the  coronary  artery.  We  may  therefore  conclude  that 
in  the  mammalian,  as  in  the  amphibian,  heart  the  cause  of  the  rhythm 
is  to  be  sought  in  the  properties  of  the  muscle  fibres  themselves,  and 
that  every  part  of  the  heart-muscle  possesses  the  power  of  rhythmic 
activity,  the  normal  sequence  of  the  beats  being  determined  by  the 
greater  frequency  of  the  natural  rhythm  of  the  venous  end  of  the 
heirt. 

As  in  the  amphibian  heart,  the  electrical  changes  may  be  used  as 
an  index  of  the  course  and  time-relations  of  the  excitatory  wave 
in  the  mammalian  heart.  "Waller  first  showed  that  the  electrical 
changes  in  the  human  heart  might  be  recorded  by  leading  oS  two 
parts  of  the  body  (v.  Fig.  432),  properly  placed,  to  an  electrometer ; 


i'lG.  i'.y.i.     Electrocardiogram  of  man.  obtained  by  leading  oti  from  the  two 
hands  to  a  string  galvanometer. 
V  is  the  carotid  pulse  tracing.     The  different  parts  of  the  curve  are  desig- 
nated by  the  letters  P,  Q,  K,  S,  T,  first  applied  to  them  bj-  Einthoven. 

and  Bayliss  and  I,  from  the  human  heart,  leading  off  the  chest  wall 
over  the  apex  beat  and  the  right  hand  to  the  capillary  electrometer, 
obtained  a  triphasic  variation  similar  to  that  recorded  for  the  frog.  At 
that  time  we  interpreted  the  curves  as  indicating  that  the  excitatory 
process  at  the  base  of  the  ventricle,  though  beginning  before,  out- 
lasted the  excitatory  condition  at  the  apex.  More  recent  and  better 
curves  obtained  by  Einthoven,  both  with  the  capillary  electrometer 
and  the  string  galvanometer,  show  that  the  changes  are  somewhat 
more  complex.  A  human  electrocardiogram,  obtained  by  Einthoven, 
is  given  in  Fig.  433.  In  this  case  the  right  and  left  hands  were 
connected  with  the  terminals  of  a  string  galvanometer.  With  this 
arrangement  the  right  hand  may  be  regarded  as  leading  off  from  the 
base,  while  the  left  hand  leads  off  from  the  apex  of  the  heart.  In 
the  curve,  '  negativity  '  of  the  base,  i.e.  of  the  auricular  end  of  the 
heart,  is  indicated  by  a  movement  upwards,  and  vice  versa.  In  the 
curve  the  excursion  p  is  certainly  due  to  the  auricular  contraction. 


1070 


PHYSIOLOGY 


The  movement  in  the  reverse  direction  at  q  may  either  represent  the 
passing  ofE  of  the  auricular  contraction,  or,  more  probably,  the  beginning 
of  the  ventricular  contraction  somewhere  near  the  apex,  e.g.  in  the 
neighbourhood  of  the  papillary  muscles.  The  large  wave  R  is  certainly 
due  to  contraction  of  the  base  of  the  ventricles,  and  the  rapid  descent 
of  the  curve  signifies  the  spread  of  the  excitation  wave  over  the  whole 
heart,  involving  the  apex.  The  wave  t  is  almost  certainly  due,  as 
the  similar  excursion  in  the  electrocardiogram  of  the  frog's  ventricle, 

to  the  contraction  of  muscle  fibres 
surrounding  the  root  of  the  aorta 
and  the  pulmonary  artery,  corre- 
sponding to  the  bulbus  aortas  in 
the  frog. 

The  explanation  of  the  order  of 
the  different  phases  in  the  curve 
of  the  electrical  changes  is  to  be 
sought  in  the  arrangement  of  the 
muscular  bundles  or  associated  tis- 
sues which  are  responsible  for  the 
propagation  of  the  wave  through 
the  heart.  In  the  primitive  verte- 
brate heart,  as  Keith  has  shown, 
we  may  distinguish  five  chambers, 
namely,  the  sinus  venosus,  the  auri- 
cular canal,  the  auricle,  the  ven- 
tricle (Fig.  434)  and  the  bulbus 
(Fig.  434).  The  musculature  of  these 
chambers  is  continuous  through- 
out. In  the  adult  heart,  e.g.  of 
man,  the  anatomical  relations  of 
the  different  cavities  have  become 
considerably  modified  in  the 
course  of  development.  The  sinus 
venosus,  i.e.  the  part  where  in  the  lower  vertebrates  the  contraction 
wave  takes  its  origin,  is  now  represented  merely  by  the  termination 
of  the  superior  vena  cava  and  of  the  coronary  sinus  in  the  right  auricle. 
These  two  veins  are  derived  from  the  right  and  left  ducts  of  Cuvier  in 
the  embryo.  The  sinus  venosus  is  also  represented  by  a  small  amount 
of  tissue  underlying  the  tcenia  terminalis  of  the  right  auricle,  as  well 
as  by  the  remains  of  the  Eustachian  and  venous  valves.  The  auricular 
canal  gives  rise  to  the  auricular  septum  and  t^  the  auricular  ring  sur- 
rounding the  auriculo-ventricular  orifice,  and  in  some  hearts  it  is 
prolonged  into  the  ventricle  as  the  intraventricular  or  invaginated 
part  of  the  auricular  canal.     This  intraventricular  part  is  not  at  first 


Fig 


434.  A  generalised  type  of  verte- 
brate heart.  (Keith.) 
a,  sinus  venosiis ;  6,  auricular  canal ; 
c,  auricle ;  d,  ventricle ;  e,  bulbus  cordis ; 
/,  aorta ;  1-1,  sino-auricular  junction  and 
venous  valves ;  2-2,  canalo-auricular 
junction;  3-3,  annular  part  of  auricle; 
4-4,  invaginated  part  of  auricle ;  5, 
bul  bo -ventricular  junction. 


THE  CAUSATION  OF  THE  HEART-BEAT  1071 

sight  evident  in  the  adult  heart.  On  superficial  dissection  the  muscle 
fibres  both  of  auricles  and  ventricles  are  seen  to  arise  from  a  fibro- 
cartilaginous ring  surrounding  the  auriculo-ventricular  junctions, 
leaving  apparently  no  muscle  continuous  between  the  two  cavities- 
On  this  account  it  was  thought  for  many  years  that  the  propagation 
of  the  contraction  from  auricles  to  ventricles  must  occur  by  means  of 
nerve  fibres.  It  was  shown  by  Wooldridge  and  Tigerstedt  that  com- 
plete destruction  of  functional  continuity  between  auricles  and 
ventricles  caused  a  failure  of  the  sequence  of  contractions  between 


^\ 


Fig.  435.  Left  ventricle  laid  open  to  display  the  interventricular  septum 
on  which  the  course  of  the  auriculo-ventricular  bundle  and  its  ramifi- 
cations are  shown  in  black.     (After  Tawara.) 

these  two  cavities,  so  that  after  the  operation  the  auricles  might  be 
beating  at  80  per  minute,  while  the  ventricle  rhythm  was  only  20  to 
40  per  minute.  Bayliss  and  I  found  that  in  the  normal  mammalian 
heart  it  was  possible  to  reverse  the  normal  sequence  of  rhythm  by 
artificially  stimulating  the  ventricles  at  a  rate  greater  than  the  normal 
rhythm.  It  is  difficult  to  conceive  of  any  arrangement  of  neurons 
which  would  propagate  impulses  impartially  from  auricles  to  ventricles 
or  from  ventricles  to  auricles.  Such  a  condition  would  seem  to  be  in 
contradiction  to  the  '  law  of  forward  direction  '  which  we  find  to 
obtain  throughout  the  nervous  system.  The  dilliculty  of  explaining 
the  phenomenon  of  reversed  rhythm  disappeared  when  it  was  shown 
by  Stanley  Kent  that  there  is  actually  a  continuity  of  muscular 
fibres  between  the  auricles  and  ventricles.     Kent's  observations  were 


1072 


PHYSIOLOGY 


confirmed  independently  by  His,  and  the  muscular  bundle  running 
between  these  cavities  has  since  been  known  as  the  bundle  of  His,  or, 
better,  as  the  auriculo-ventricular  bundle.  This  bundle,  in  the 
human  heart,  is  in  close  connection  with  the  fibres  of  the  interauricular 
septum  and  with  the  tissue  at  the  junction  of  the  superior  vena  cava 
with  the  right  auricle  (the  sino-auricular  node  of  Flack  and  Keith), 
which,  as  we  have  seen,  represents  the  sinus  venosus  of  the  primi- 
tive heart.  The  bundle  arises  in  the  auriculo-ventricular  node  which 
lies  at  the  base  of  the  auricular  septum  on  the  right  side,  below  and 
to  the  right  of  the  coronary  sinus.  From  this  point  the  bundle  runs 
along  the  top  of  the  interventricular  septum  just  below  its  membranous 
part,  and  then  di\ndes  into  the  right  and  left  septal  divisions  which 
run  down  in  each  ventricle  on  the  interventricular  septum  and  pass 


Fig.  436.     Fibres  of  Purkinje,  from  a  strand  of  the  a. v.  bundle.     (Tawaka.) 


into  the  papillary  muscles  arising  from  the  septum  (Fig.  435).  From  the 
papillary  muscles  fine  bands  or  delicate  strands  run  to  the  ventricular 
muscle  near  the  apex  of  the  ventricle.  It  is  easy  to  determine  the 
course  of  the  bundle  in  sections  of  the  heart  since  the  muscle  fibres 
composing  it  are  of  a  more  primitive  character  than  the  rest  of  the 
cardiac  musculature,  and  have  indeed  long  been  known  and  dis- 
tinguished under  the  name  of  the  '  fibres  of  Purkinje  '  (Fig.  4.36).  It 
is  found  that  division  of  this  bundle  absolutely  destroys  functional 
continuity  between  auricles  and  ventricles. 

The  fibres  of  the  auriculo-ventricular  bundle  may  be  destroyed 
by  disease.  In  such  cases  we  get  a  series  of  phenomena  known  under 
the  name  of  Stokes-Adams'  disease,  the  main  characteristic  of  which 
is  the  slow  contractions  of  the  ventricle,  accompanied  by  a  rapid 


THE  CAUSATION  OF  THE  HEART-BEAT 


1073 


venous  pulse  at  a  rhythm  entirely  independent  of  the  ventricular  pulse. 
The  automatic  activities  of  auricle  and  ventricle  are  in  fact  dissociated 
(Fii^.  437).  At  certain  intervals,  or  at  certain  stages  of  the  disease, 
the  fibres  of  the  bundle  may  present  only  a  partial  block,  so  that  the 
ventricle  responds  once  to  every  second  contraction  of  the  auricle. 
The  course  of  the  fibres  of  the  auriculo-ventricular  bundle  probably 
throws  light  on  the  path  taken  by  the  excitatory  process  in  its  passage 
through  the  heart.  We  may  regard  the  contraction  of  the  mammalian 
heart  as  starting  in  the  tissue  between  the  superior  cava  and  the  coronary 
sinus,  the  sino-auricular  node,  and  as  spreading  from  here  to  the 
auricular  septum  and  thence  over  both  auricles.  At  the  same  time 
it  is  spreading  along  the  auriculo-ventricular  bundle  to  the  ventri- 


Roid.art. 


Fig.  437.  Simultaneous  tracings  of  the  jugular  venous  pulse  and  the  radial 
arterial  pulse,  from  a  case  in  which  the  A.V.  bundle  was  destroyed  by 
disease.  The  contractions  of  the  auricles  are  marked  b\'  the  a  waves 
on  the  venous  pulse.  They  are  more  rapid  than  and  quite  independent 
of  the  ventricidar  contractions.     (Mackenzie.) 


cular  septum,  to  the  papillary  muscles,  and  to  the  rest  of  the  heart, 
reaching  first  the  base  and  later  spreading  to  the  apex.  Last  of  all 
it  reaches  the  neighbourhood  of  the  pulmonary  artery,  that  part,  in 
fact,  w^hich  corresponds  to  the  bulbus  aortae.  We  can  thus  under- 
stand why  we  get  the  polyphasic  variation  on  leading  ofE  the  mam- 
malian heart  in  situ  to  the  capillary  electrometer,  why,  as  shown  by 
Roy  and  Adami,  the  papillary  muscles  contract  slightly  before  the 
rest  of  the  ventricular  wall,  and  why  under  certain  conditions,  e.g.  of 
vagus  stimulation,  one  may  get  a  ventricular  contraction  at  a  normal 
rhythm  and  strength,  while  the  auricular  contractions,  as  judged  by 
the  movements  of  the  auricular  appendages,  have  been  reduced  to 
disappearance.  In  the  last  case  the  rhythmic  excitatory  process 
can  still  spread  from  its  point  of  origin  along  the  auriculo-ventricular 
bundle  to  the  ventricles.  Numerous  nerve  fibres  and  ganglion-cells 
are  found  to  accompany  the  muscle  fibres  of  the  auriculo-ventricular 
bundle.  We  have,  however,  no  reasons  for  regarding  the  nervous 
structures  as  concerned  in  the  propagation  of  the  excitatory  wave. 

68 


1074  PHYSIOLOGY 

THE  PHYSIOLOGICAL  PROPERTIES  OF  THE  CARDIAC 

MUSCLE 

THE   RESPONSE  OF   HEART-MUSCLE  TO   DIRECT  EXCITATION 

When  a  skeletal  muscle  is  directly  stimulated  with  induction 
shocks  of  varying  strength,  within  narrow  limits  the  height  of  the 
contraction  is  proportional  to  the  strength  of  the  stimulus.  If  the 
frog's  ventricle,  rendered  motionless  by  a  Stannius  ligature,  be  stimu- 
lated with  a  single  induction  shock,  if  it  responds  at  all  it  will  respond 
with  a  maximal  contraction,  no  change  in  the  extent  of  the  contraction 
being  obtainable,  however  the  stimulus  may  be  increased.  There  is 
thus  no  proportionality  in  the  heart  between  strength  of  stimulus  and 
height  of  contraction.  The  heart,  if  it  contracts  at  all,  always  con- 
tracts to  its  utmost,  the  height  of  the  contraction  being  dependent, 
not  on  the  strength  of  stimulus,  but  on  other  conditions  affecting  the 
muscle  at  the  time  of  its  response. 

Although  much  stress  has  been  laid  on  this  supposed  difference 
between  heart-muscle  and  voluntary  muscle,  a  renewed  investigation 
of  the  response  of  the  latter  to  graded  stimuli  by  Gotch  and  by  Keith 
Lucas  tends  "to  show  that  the  distinction  is  not  so  fundamental. 
According  to  these  observers  the  fact  that  the  response  to  a  minimal 
stimulus  in  skeletal  muscle  is  smaller  than  the  response  to  a  maximal 
stimulus  is  simply  owing  to  the  fact  that  in  the  former  case  only  a 
small  proportion  of  the  muscle  fibres  is  active  and  that  increasing  the 
strength  of  the  stimulus  merely  increases  the  number  of  fibres  thrown 
into  contraction.  According  to  this  view  therefore  a  maximal  contrac- 
tion of  skeletal  muscle  would  be  one  involving  all  the  fibres.  In  the 
heart-muscle  all  the  muscle  fibres  are  functionally  continuous,  so  that 
a  stimulus,  if  it  excites  at  all,  must  excite  all  the  fibres,  and  ever}^ 
contraction  must  be  analogous  to  the  maximal  contraction  of  a  skeletal 
muscle.  The  existence  of  the  '  all  or  none  '  law  in  any  contractile  tissue 
would  be  therefore  dependent  on  the  existence  of  functional  continuity 
between  all  the  contractile  elements  of  the  tissue. 

In  the  retractor  penis  of  the  dog  it  is  possible  to  get  graded  con- 
tractions with  graded  strength  of  stimuli,  and  in  this  case  it  is  easy  to 
observe  that  with  increasing  strength  of  stimulus  a  greater  extent  of 
the  muscle  is  thrown  into  the  contractile  state.  Closely  connected 
with  this  manner  of  response  is  the  fact  that  in  heart-muscle,  under 
normal  circumstances,  it  is  not  possible  to  get  summation  of  contrac- 
tions by  putting  in  a  stimulus,  however  strong,  before  the  muscle  has 
returned  to  rest.  If,  however,  the  propagation  of  the  first  contraction 
throughout  the  heart-muscle  be  retarded  or  prevented  by  a  partial 
death  of  the  tissue,  or  by  stimulus  of  the  vagus  nerve,  it  is  possible,  as 
Frank  has  shown,  to  obtain  an  apparent  summation  of  two  stimuli,  i.e. 


THE  CAUSATION  OF  THE  HEART-BEAT 


1075 


a  curve  in  which  the  second  contraction  is  superposed  on  and  rises 
higher  than  the  first.  Such  a  result,  on  the  explanation  given  above, 
would  be  due  to  a  phenomenon  of  '  block '  limiting  the  propagation 
of  the  first  contractile  wave,  and  yielding  more  to  the  second,  though 
this  is  not  the  explanation  given  by  the  original  observer. 

SUMMATION   OF   STIMULI 

If  an  isolated  frog's  ventricle  which  is  not  beating  be  stimulated 
with  inadequate  shocks,  it  may  be  found,  on  repeating  these  shocks  at 
short  intervals  of  time,  that  they  become  adequate  and  cause  a  con- 
traction of  the  ventricle.  A  stimulus  therefore  which  is  subminimal 
may  nevertheless  cause  some  change  in  the  heart-muscle,  so  that  the 
latter  responds  more  readily  to  subsequent  stimuli. 

A  similar  improving  effect  of  previous  stimulation  on  the 
condition  of  the  heart-muscle  may  be  observed 
on  the  contractions  themselves.  Thus  in  a 
Stannius  preparation,  if  the  ventricle  be  excited 
with  single  induction  shocks,  once  in  every  ten 
seconds,  the  first  four  or  five  contractions 
form  an  ascending  series,  each  contraction 
being  rather  higher  than  the  preceding  one. 
This  is  often  spoken  of  as  the  '  staircase   phenomenon  '  (Fig.  438). 


Fig.  4:38.  Gruiip  of  pul- 
sations sho\\ing '  stair- 
case '  character. 


^^  THE  REFRACTORY  PERIOD 
At  each  contraction  of  the  heart-muscle  there  is  a  sudden  decom- 
position of  contractile  material  which,  so  far  at  least  as  concerns  the 
incidence  of  an  external  stimulus,  is  maximal,  i.e.  complete.  Directly 
this  has  occurred  a  process  of  assimilation  or  re-formation  of  contractile 
material  begins.  This  lasts  throughout  the  diastolic  period,  and  the 
store  of  contractile  material  is  at  its  maximum  just  before  the  next 
contraction.  A  mechanical  analogy  is  furnished  by  a  bucket  into 
which  a  stream  of  water  is  constantly  flowing,  and  which  tips  up 
automatically  and  empties  out  its  contents  as  soon  as  the  water  reaches 
a  certain  height.  It  is  evident  that  the  power  of  the  heart-muscle  to 
contract  in  response  to  a  stimulus  (its  '  irritability  ')  must  be  at  a 
mininmm  immediately  after  the  automatic  discharge  or  decomposition 
has  taken  place,  and  will  continually  increase  from  this  point  as  the 
store  of  contractile  material  grows,  until  it  arrives  at  such  a  height 
that  the  explosive  discharge  occurs  s|Jontaneou8ly.  Hence  in  each 
cardiac  cycle  there  is  a  period,  known  as  the  refractory  period,  in 
which  stimuli  applied  to  the  heart  have  no  effect.  This  will  be  followed 
by  a  period  in  which  a  stimulus  is  followed  by  an  extra  contraction, 
but  with  a  prolonged  latent  period.  Just  before  the  next  spontaneous 
contraction  the  irritability  is  at    its  height,  and    the    heart-nmscle 


1076 


PHYSIOLOGY 


responds  with  a  contraction  to  a  minimal  stimulus.     These  facts  are 
well  shown  in  Fig.  439. 

When  a  tracing  is  being  taken  from  part  of  the  heart,  e.g.  the 
ventricle,  which  is  beating  rhythmically  in  consequence  of  a  stimulus 
communicated  to  it  from  some  other  part,  such  as  the  sinus  venosus. 


Fig.  439.  Tracings  of  spontaneous  contractions  of  frog's  ventricle,  to  show 
refractory  period.  In  each  series  the  surface  of  the  ventricle  was  stimu- 
lated by  an  induction  shock  at  E,  as  indicated  by  the  tracing  of  the  signal. 
In  1,  2  and  3  this  stimulus  had  absolutely  no  effect,  since  it  fell  during 
the  refractory  period.  In  4,  5,  6,  7  the  effect  of  the  shock  was  to  inter- 
polate an  extra  contraction  in  the  series,  the  latent  period  (shaded  part) 
gradually  diminishing  from  4  to  7  (diastolic  rise  of  irritability).  In  8 
the  irritability  of  the  preparation  was  already  considerable,  and  the 
latent  jieriod  inappreciable.  The  '  comijensatory  pause  '  after  the  extra 
beat  is  also  well  shown  in  4,  5,  6,  7,  8.     (Mare v.) 

an  extra  contraction  is  follo^fed  by  a  '  compensatory  pause,'  and 
in  certain  cases  the  first  contraction  following  the  pause  is  con- 
siderably augmented.  This  is  due  to  the  fact  that  one  of  the  impulses 
arriving  from  the  sinus  arrives  at  the  ventricles  during  the  refractory 
period  ensuing  on  the  application  of  the  artificial  stimulus ;  hence  it 
produces  no  effect  and  the  ventricle  has  to  wait  for  the  arrival  of  the 


THE  CAUSATION  OF  THE  HEART-BEAT  1077 

next  succeeding  excitatory  wave  from  the  sinus  before  it  gives  its  next 
beat.  Hence  the  compensatory  pause  does  not  occur  when  we  are 
testing  the  effects  of  artificial  stimuli  on  the  sinus  venosus. 

On  account  of  the  refractory  period  which  ensues  on  the  com- 
mencement of  the  contractile  process  on  heart  muscle,  it  is  impossible 
to  throw  the  muscle  into  a  tetanus,  since  all  the  stimuli  which  fall 
during  systole  are  entirely  ineffective.  By  using  very  strong  stimuli 
it  is  possible  to  intercalate  extra  contractions  before  the  heart  has 
returned  to  the  base  line,  i.e.  before  diastole  is  complete.  So  that  in 
this  way  one  may  obtain  almost  a  continuous  contraction,  presenting, 
however,  waves  on  its  summit,  which  differs  from  the  tetanus  of  skeletal 
muscle  in  the  fact  that  its  height  is  no  greater  than  the  height  of  a  single 
contraction. 

Only  when  the  functional  continuity  of  the  heart-muscle  is  im- 
paired by  the  '  block  '  effect  of  vagal  stimulation  or  the  administration 
of  muscarine  is  it  possible  to  obtain  phenomena  even  superficially 
analogous  to  the  summation  of  contractions  in  skeletal  muscle. 

FACTORS  MODIFYING  THE  ACTIVITY  OF  CARDIAC 
MUSCLE 

INFLUENCE  OF  TENSION 

The  most  important  factor  in  determining  the  strength  and 
extent  of  the  cardiac  contractions  is  the  tension  on  the  muscle  fibres. 
Within  certain  limits  the  energy  of  contraction  of  the  cardiac  muscle 
increases  with  tension,  i.e.  with  the  resistance  to  the  shortening  to 
which  the  muscle  fibre  is  exposed.  This  effect  can  be  seen  when  the 
resistance  to  the  outflow  of  blood  from  the  heart  is  increased,  so  that  the 
resistance  is  only  experienced  during  the  contraction  of  the  heart- 
muscle.  It  is  still  better  marked  when  the  muscle  fibres  are  stretched 
by  the  distending  force  before  they  begin  to  contract,  i.e.  during 
diastole.  In  this  case,  as  is  shown  in  Fig.  440,  the  heart  contracts  more 
forcibly  the  .greater  its  distension  during  the  diastolic  period.  In  the 
experiment  from  which  this  figure  was  derived,  the  heart  was  con- 
tracting isometrically,  i.e.  was  given  a  tension  which  it  was  unable 
to  overcome,  so  that  the  length  of  its  fibres  was  not  altered  during  the 
act  of  contraction.  This  reaction  of  the  cardiac  muscle  to  tension 
plays  a  great  part  in  determining  the  adaptation  of  the  heart,  both  in 
the  cold-blooded  and  in  the  higher  animals,  to  variations  in  the  load, 
i.e.  variations  in  the  pressure  it  has  to  overcome  and  in  the  amount  t  f 
blood  which  it  has  to  expel. 

Thus  if  a  ligature  be  placed  round  the  aorta  so  as  to  narrow  the 
vessel  to  one-third  of  its  normal  extent,  the  arterial  pressure,  as  judged 
by  a  manometer  connected  with  the  carotid  artery,  undergoes  no  change. 
If,  however,  the  pressure  be  taken  in  the  intraventricular  cavity  each 


1078 


PHYSIOLOGY 


contraction  will  be  found  to  be  associated  with  a  rise  of  pressure  which 
may  be  double  or  treble  the  normal  extent,  the  arterial  pressure 
being  kept  at  its  normal  height  at  the  expense  of  additional  work  on 
the  part  of  the  heart-muscle.  This  adaptation  takes  place  even  after 
division  of  all  the  nerves  which  run  from  the  central  nervous  system 
to  the  heart,  and  is  due  entirely  to  the  reaction  of  the  muscle  fibres 
of  the  ventricles  to  the  resistance  which  they  have  to  overcome,  i.e. 
to  the  tension  to  which  they  are  subjected. 

We  have  already  seen  that  increased  venous  pressure  leads  to 
increased  diastolic  filling  of  the  heart,   and  that  a   distended  heart 

is  mechanically  in  a   less  favourable 
condition   for    expelling   its   contents 
[v.  p.  1032).     Nevertheless  a  healthy 
heart    reacts    to    increased    diastolic 
filling  by   increased  systolic    output. 
The     muscle    fibres,     stimulated    by 
their   increased   tension  during   dias- 
tole,   contract    more  forcibly   and  to 
a  greater  extent ;  so  that  the  residual 
volume  of  blood  in  the  heart  at  the 
end  of  systole  may  be  very  little  or 
no  greater   than   it   is  in  the  undis- 
FiG.  440.     Isometric  contractions  of    tended  heart, 
frog's  ventricle.      The  initial  ten- 
sion   was    continually    increased       This  property  of  the  cardiac  muscle 
from  curve  1  to  curve  6,  each  in-    •.     responsible    for     the     power    of 


crease  of  tension  causing  a  greater 
energy  of  contraction,  (v.  Frank.) 


IS 


compensation  '  possessed  by  a  dis- 
eased heart.  We  may  take  as  an 
example  the  destruction  of  one  aortic  valve,  a  lesion  which  can  be 
produced  experimentally  in  a  dog.  In  this  case,  immediately  after 
the  lesion  is  established,  no  additional  resistance  is  offered  to  the 
expulsion  of  the  blood,  and  the  ventricle  will  send  the  normal  amount 
into  the  aorta.  During  the  succeeding  diastole  the  blood  at  a  high 
pressure  in  the  aorta  vnW  leak  back  into  the  ventricle  through  the 
damaged  valve.  The  arterial  pressure  therefore  falls  rapidly,  and 
the  ventricle  receives  blood  from  two  sides,  i.e.  by  regurgitation 
through  the  aortic  valves,  and  in  the  normal  way  from  the  auricles  and 
veins.  At  the  end  of  diastole  the  ventricle  is  therefore  overfilled. 
Increased  stretching  of  its  fibres,  however,  has  the  effect  of  exciting 
an  increased  contraction,  and  the  heart  at  its  next  systole  throws  out 
not  only  the  normal  quantity  of  blood  but  also  that  which  it  has 
received  back  from  the  aorta.  The  arterial  system  thus  receives  at 
each  beat  the  normal  quantity  of  blood  flus  the  amount  which  leaks 
back  into  the  ventricle  between  each  systole  ;  so  that  the  amount 
of  blood  remaining  in  the  aorta  and  available  for  passage  on  to  the 


THE  CAUSATION  OF  THE  HEART-BEAT  1079 

capillaries  is  the  same  as  in  the  normal  animal.  On  this  account, 
after  a  lesion  of  the  aortic  valves  has  been  established,  the  average 
of  the  arterial  pressure  remains  the  same  as  before,  although  the 
oscillations  of  pressure  with  each  heart-beat  are  increased  in  extent. 
The  augmented  output  by  the  ventricles  naturally  involves  increased 
work  on  the  part  of  their  muscular  walls,  which  react  in  the  same 
way  as  skeletal  muscle  does  to  increased  work,  i.e.  by  hyper- 
trophy ;  the  final  effect  therefore  is  a  heart  bigger  than  normal,  with 
hypertrophied  and  thickened  walls,  but  capable  of  maintaining  an 
adequate  circulation  throughout  all  parts  of  the  body ;  in  other  words, 
in  the  healthy  animal  complete  compensation  has  taken  place. 

THE   INFLUENCE   OF  TEMPERATURE   ON  THE   HEART   RATE 

Tlio  frequency  of  the  heart  varies  directly  with  the  temperature* 
The  higher  the  temperature  the  greater  the  frequency.  At  40^  C.  the 
contraction  of  the  mammalian  heart  may  be  four  times  as  frequent  as 
at  15°  C. 

\ 


Fig.  441.  Tracing  of  contractions  of  a  frog's  heart  (by  Ringer),  showing 
effect  of  adding  a  trace  of  CaClo  to  the  NaCl  solution  used  previously  for 
perfusion.     The  arrow  marks  the  point  at  which  the  addition  was  made. 

INFLUENCE  OF  THE  CHEMICAL  COMPOSITION  OF  THE 
SURROUNDING  MEDIUM  ON  THE  HEART-MUSCLE 
The  tissues  of  the  heart,  like  all  other  cells  of  the  body,  require 
for  the  normal  display  of  their  functions  a  definite  osmotic  environ- 
ment, i.e.  a  certain  molecular  concentration  of  the  fluid  with  which 
they  are  bathed.  This  is  equivalent  to  a  0-65  per  cent,  sodium 
chloride  solution  for  the  frog's  heart,  and  to  a  0'9  per  cent,  solu-  iL 
tion  for  the  mammalian  heart.  As  Ringer  first  showed,  the  nature 
of  the  neutral  salt  employed  for  making  up  the  normal  solution 
is  all-important  to  the  heart-muscle.  Thus  a  strip  of  muscle  from 
the  apex  of  the  tortoise's  ventricle  as  a  rule  does  not  beat  spon- 
taneously. If,  however,  it  be  immersed  in  a  (>7  per  cent,  solution 
of  sodium  chloride  it  begins  to  beat  rhythmically  after  a  short  latent 
period.  The  contractions  soon  reach  a  maximum  and  then  gradiiallv 
die  away.  Sodium  chloride  therefore  acts  as  a  stimulus  to  contraction, 
but  is  unable  to  maintain  the  beats  for  any  considerable  length  of 
time.  The  strip  of  muscle  ceases  contracting  in  a  condition  of  relaxa- 
tion. On  now  adding  to  the  solution  a  trace  of  calcium  chloride  or 
calcium   sulphate,  the  contractions  begin  again  (Fig.    i\\).      Now, 


1080  PHYSIOLOGY 

however,  the  relaxations  after  each  contraction  become  more  and  more 
incomplete,  nntil  finally  the  heart  stops  in  a  tonically  contracted  con- 
dition. If  now  a  trace  of  potassium  chloride  or  phosphate  be  added  the 
contractions  begin  again  and  may  last  for  many  hours,  although  the 
solution  contains  nothing  which  can  furnish  energy  to  the  contracting 
muscle.  It  has  been  suggested  that  the  rhythmic  contractions  of  the 
heart-muscle  may  be  the  result  of  the  constant  chemical  stimulus  of 
the  inorganic  salts  present  in  the  blood-plasma,  sodium  acting  as  a 
stimulus  to  contraction,  while  the  calcium  salts  are  necessary  for  the 
maintenance  of  the  systolic  tone,  and  the  potassium  salts  for  the 
occurrence  of  relaxation. 

The  exact  significance  of  these  different  salts  for  the  functions  of 
cardiac  and  other  forms  of  muscular  tissue,  though  they  have  been  the 
subject  of  many  detailed  investigations,  must  be  still  regarded  as  an 
open  question. 

The  fluids  containing  the  three  salts  mentioned   above  in  slightly 


Fig.  442.  A  frog's  heart  poisoned  by  excess  of  calcium  salts,  recovers  its  sponta 
neons  rhythm  on  adding  a  trace  of  KCl  to  the  perfusion  fluid.    (Ringer.) 

varying  proportions  are  commonly  used  to  maintain  the  beat  in  an 
excised  heart  either  of  a  cold-  or  of  a  warm-blooded  animal.  In  the 
case  of  the  latter  it  is  necessary  to  keep  the  fluid  saturated  with  oxygen. 
According  to  Locke  the  addition  of  glucose  to  the  solutions  enables 
the  beats  to  go  on  for  a  longer  period  of  time,  and  will  in  fact  renew 
the  rhythm  of  a  heart  which  has  ceased  beating  while  being  fed  with 
pure  saline  solution. 

The  following  represent  the  fluids  most  frequently  used  : 

Ringer's  Fluib 

(for  frog's  heart) 

1  per  cent,  sodium  bicarbonate    .  .  .  .  .  1  c.c. 

1         ,,         calcium  chloride  .  .  .  .  .  1  c.c. 

1         „         potassium  chloride      .....  0'75  c.c. 

0'6     „         sodium  chloride  ....         to  100  c.c. 

Locke's  Fluid 
(for  mammalian  heart)" 
0'015  per  cent,  sodium  bicarbonate, 
0*024         „         calcium  chloride, 
0"042         „         potassium  chloride, 
0"92  „         sodium  chloride, 

O'l  „         glucose, 

in  distilled  water. 


THE  CAUSATION  OF  THE  HEART-BEAT 


1081 


The  influence  of  the  chemical  composition  of  tlie  medium  on  the  contraction 
of  the  heart  may  be  investigated  in  the  following  ways  : 

One  of  the  simplest  methods  is  that  emploj'cd  by  Gotch,  represented  in  the 
diagram  (Fig.  443).  The  apparatus  consists  of  a  small  glass  jar  with  inlet  and 
outlet  tubes.  A  disc  of  cork  is  fixed  on  to  a  brass  rod  so  that  it  can  be  let  down 
into  the  fluid.  On  the  upper  end  of  the  brass  rod  is  poised  a  light  lever  ^nth  a 
paper  point.    To  fix  the  licart  in  the  apparatus,  the  top  of  the  ventricle  is  trans- 


FiLi.  44;j.     Ciotch's  frog  licait  apparatus. 

fixed  by  a  fine  hook  to  wlxich  is  attached  a  thread  connected  with  the  lever. 
The  heart  is  fastened  to  the  cork  by  a  pin  through  the  bulbus  aorta?.  Tlie  glass 
jar  is  fiUetl  with  the  fluid  whose  action  it  is  desired  to  investigate.  It  is  usual  to 
start  witli  Ringer's  fluid  in  order  to  obtain  a  normal  beat,  and  then  to  try  in 
turn  the  various  constituents  of  tliis  fluid. 

Another  method  of  investigating  the  action  of  tho  heart  of  cold-blooded 
animals  is  by  perfusing  the  heart  cavities  with  tho  fluid  under  investigation. 
Two  forms  of  perfusion  are  made  uso  of.  In  tho  method  first  introduced  by 
Williams  a  double  cannula  is  tied  into  tho  ventricle,  the  rest  of  the  heart  being 
cut  away.  Tlie  tubes  leading  to  and  away  from  tlie  perfusion  cannula  are  armed 
^nth  valves  so  as  to  allow  the  fluid  only  to  pass  in  one  direction.  The  contractions 
of  tho  ventricle  may  be  recorded  cither  by  connecting  tho  outgoing  tube  with  a 
manometer,  which  may  be  a  mercurial  or  a  membrane  manometer,  or  by  con- 
necting some  form  of  recording  apparatus  with  tho  vessel  in  which  tho  heart  is 


1082 


PHYSIOLOGY 


contained,  so  as  to  register  changes  in  the  volume  of  the  ventricle.     A  large 
number  of  different  forms  of  apparatus  have  been  devised  for  these  purposes. 

In  another  method  the  fluid  is  allowed  to  flow  tlu-ough  the  whole  heart, 
passing  in  by  the  sinus  and  out  by  the  aorta.  Here  again  the  activity  of  the 
heart  may  be  registered  either  by  recording  the  pulsations  in  the  arterial  column 
of  fluid  or  by  connecting  a  tambour  or  piston  recorder  with  the  vessel  in  which 
the  heart  is  contained. 

The  heart  of  warm-blooded  animals  can  also  be  investigated  by  a  somewhat 
similar  method.  It  was  shown  by  Porter  that  the 
mammalian  heart  could  be  kept  alive  by  transfusing 
defibrinated  blood  through  the  coronary  vessels, 
and  Locke  found  that  the  same  results  could  be 
obtained  by  using  oxygenated  Ringer's  solution, 
modified  so  as  to  have  the  same  tonicity  as  mam- 
maUan  blood.  A  convenient  apparatus  for  this 
purpose  has  been  devised  by  Brodie. 

The  apparatus  (Fig.  444)  consists  of  a  chamber 

A  to  contain  the  heart,  and  of  a  tube  b,  through 

which  the  perfusion  fluid  is  carried  to  the  heart.   Both 

are  enclosed  in  a  large  outer  jacket  c,  through  which  is 

kept  flowing  a  stream  of  water  at  body  temperature. 

The  chamber  a  is  beU-shaped  and  is  fitted  into  the 

jacketing  tube  c  by  a  ground-glass    joint  D.      Its 

upper  orifice  is  closed  by  a  piece  of  rubber  tubing 

of  such  size  that  the  perfusion  tube  b  slips  through 

it  easily.     By  means  of  the  glass  handle  F,  fused 

into  the  tube  about  half-way  down,  b  can  be  drawn 

up  or  lowered  into  any  desired  position.   To  its  lower 

end  the  heart  cannula  is  attached  by  a  ground  joint. 

Its  upper  end  is  fitted,  by  a  second  ground  joint, 

with  a  small  bulb  w,  with  two  tubes,  r  and  s,  fitted 

into  it.    These  latter  are  connected  by  rubber  tubing 

with    aspirators    contaimng    the    solutions    to    be 

perfused.     The  lower  half  of  the   tube   B   is   nearly 

filled  up  with  a  thermometer  l,  the  bulb  of  which 

projects  into  the  heart  cannula  T.    The  upper  half  is 

Fig.  444.  Brodie's  perfusion  almost  filled  with  a  piece  of  glass  tubing  sealed  at 

apparatus  for  the  mamma-  both  ends,  so  that  the  perfusion  fluid  passes  in  a 

ban  heart.  ^Ynn  layer  down   the   tube   and  thus  offers  a  large 

surface  for  heating   purposes.      Also  by  filling  the 

interior  of  the  tube  in  this  way  its  capacity  is  reduced  to  a  very  small  amount. 

The  large  outer  tube  c  is  kept  suppUed  with  warm  water,  entering  through 

the  tube  G  and  overflowing  through  a  side-tube  at  the  top  into  a  wide  T-piece  n. 

By  raising  or  lowering  this  T-piece  the  level  of  the  water  in  the  jacket  is  adjusted. 

The  water-supply  comes  from  a  cold-water  tap,  but  on  its  passage  to  G  passes 

through  a  metal  spiral  heated  bj'  a  Bunsen  burner.    By  varying  the  rate  of  flow 

and  tlic  position  of  the  burner  the  temperature  of  the  water  can  be  regulated 

with  considerable  accuracy.     The  upper  end  of   the  supply-tube  G  is  provided 

with  a  thermometer  so  that  the  temperature  of  the  inflomng  water  can  be  seen 

and  regulated. 

In  using  the  apparatus  the  heart  cannula  is  removed,  and  the  tube  B  is  then 
passed  through  e  and  pushed  down  until  its  lower  end  issues  just  below  the  level 
of  the  chamber  a.  Tlie  circulation  of  the  warmed  water  tlirough  tlic  jacket  is 
then  started  and  adjusted  to  the  proper  temperature.    One  of  the  rubber  tubes, 


THE  CAUSATION  OF  THE  HEART-BEAT  1083 

s,  is  next  attached  to  the  reservoir  containing  the  main  perfusion  fluid,  and  the 
tube  B  filled  with  fluid  and  left  to  warm  while  the  heart  is  being  prepared. 

The  heart  having  been  excised  and  washed  well  in  saline  so  as  to  remove 
as  much  blood  as  possible,  the  cannula  is  tied  into  the  aorta.  The  cannula  is  now 
held  under  the  perfusion  tube,  filled  with  the  warm  sahne,  and  at  once  attached 
in  its  proper  position  and  the  perfusion  started.  A  bent  pin  to  which  a  long 
thread  is  tied  is  hooked  into  the  apex  of  the  heart,  and  the  perfusion  tube  pulled 
up  until  the  heart  lies  quite  within  the  warm  chamber.  When  thus  drawn  up 
the  bulb  w  lies  just  below  the  surface  of  the  water  in  the  outer  jacket.  The 
tube  is  held  firmly  in  position  by  a  clamp  which  fixes  one  arm  of  the  handle  F. 
The  heart  cannula  is  provided  with  a  side  opening  v,  on  to  which  a  long  piece 
of  fine  rubber  tubing  is  passed.    This  renders  possible  the  removal  of  any  gas 


<»W>i<**TliHill>iM«i*(lil<|>||l,H^,...^     ^  i„H|,iMllllllW(Wllt(t>WM^' 


•mm:mMmiim>»tmim<i»iTisMiA»,f^ii,ir\- 


YiG.  445.  Volume  curve  of  ventricles  (cat)  (lower  curve).  The  upper  curve 
is  the  arterial  pressure,  maintained  by  an  adjustable  resistance  at 
130  mm.  Hg.  Between  the  arrows  the  air  used  for  artificial  respiration 
was  replaced  by  a  mixture  containing  20  i)er  cent.  CO.,  and  25  per  cent, 
oxygen.  Note  the  dilatation  with  impaired  contraction,  followed  by  increased 
amplitude  of  contractions. 

bubbles  that  may  collect  in  the  cannula,  or  the  washing  out  of  the  cannula  with 
a  stream  of  fluid  if  necessary.  The  beats  of  the  heart  are  recorded  by  means  of  a 
simple  lever  attached  by  the  thread  previously  fixed  to  the  heart. 

THE   SIGNIFICANCE   OF  CARBON  DIOXIDE   FOR  THE 
HEART-BEAT 

The  blood  of  mammals  always  contains  a  certain  amount  of 
carbon  dioxide,  the  tension  of  this  gas  in  the  arterial  blood  of  man 
varying  between  5  and  6  per  cent,  of  an  atmosphere.  Henderson  has 
shown  that  if  artificial  respiration  be  maintained  so  vigorously  as  to 
wash  out  the  carbon  dioxide  from  the  blood,  the  heart's  action  is 
modified,  the  rate  being  much  quickened  and  the  relaxation  of  the 
ventricle  during  the  diastole  being  incomplete,  the  blood  pressure 
falling  in  consequence  of  the  inadequacy  of  the  heart's  action. 

It  is  easy,  by  means  of  the  isolated  lung-heart  preparation  described 
on  p.  1028,  to  demonstrate  the  importance  of  a  certain  tension  of  carbon 
dioxide  for  the  normal  beat  of  the  heart.     The  heart  is  placed  in  a 


1084 


PHYSIOLOGY 


cardiometer  so  as  to  measure  the  degree  of  its  contraction  and  relaxa- 
tion'with  systole  and  diastole,  and  also  its  output  at  each  beat. 
Artificial  respiration  being  kept  up,  the  carbon  dioxide  tension  in  the 
blood  sinks  considerably.  It  is  possible  to  administer  by  artificial 
respiration  gaseous  mixtures  containing  any  desired  quantity  of  carbon 
dioxide.  On  pumping  in  a  mixture  containing  a  certain  moderate 
amount   of   carbon    dioxide   the 


B 


U 


c 


'4'r-J^: 


D 


E 


heart  will  be  observed  to  dilate 
(Fig.  445),  but  the  dilatation 
affects  the  diastolic  volume  even 
more  than  the  systolic  volume. 
so  that  the  stroke  of  the  heart 
at  each  beat,  and  therefore  its 
output  and  efficiency,  are  in- 
creased. In  Fig.  446  are  shown 
the  cardiometer  records  obtained 
on  administration  of  a  gaseous 
mixture  containing  7-9  per  cent, 
carbon  dioxide.  The  full  effect  is 
produced  in  the  tracing  D,  where 
it  will  be  noticed  that  although 
the  heart  is  considerably  dilated, 
the  output  at  each  beat  is  in- 
creased to  such  an  extent  that 
the  contraction  becomes  more 
effective  than  before.  There  is 
an  optimum  tension  of  carbon 
dioxide  in  the  blood,  lying  be- 
tween 5  and  10  per  cent,  of  an 
atmosphere,  at  which  the  output 
of  the  ventricles  is  at  a  maximum. 
The  essential  factor  in  the  pro- 
duction of  these  results  is  probably 
the  concentration  of  hydrogen  ions  in  the  blood.  When  very  weak 
acids  are  transfused  through  the  frog's  heart  there  is  a  gradual  diminu- 
tion of  tonus,  and  the  same  relaxation  may  be  obtained  as  a  direct 
result  of  the  action  of  carbon  dioxide  or  of  weak  acids  on  the  muscular 
wall  of  the  blood-vessels. 


_n_ 


JL 


J"L 


JL 


Fig.  44G.  Cardiometer  records  of  ventri- 
cular output  (description  in  text). 
(JERU.SALEM  and  Staelixg.) 


THE  NUTRITION  OF  THE   HEART 

In  the  frog's  heart  the  muscle  fibres  are  supplied  directly  by  the 
blood  within  the  cavities,  the  spongy  ventricular  wall  permitting 
the  access  of  blood  between  the  fibres.  In  the  mammalian  heart  the 
muscular  tissue  is  nourished  through  the  coronary  arteries,  which 


THE  CAUSATION  OF  THE  HEART -BEAT  1085 

break  up  into  a  meshwork  of  capillaries  around  all  the  fibres.  The 
coronary  arteries  do  not  anastomose  with  one  another,  so  that  occlu- 
sion of  one  artery  permanently  cuts  off  the  supply  of  blood  to  the 
parts  within  its  area  of  distribution.  The  blood  enters  the  coronary 
arteries  from  the  aorta  both  during  systole  and  diastole,  though  the 
systole  of  the  ventricles  exercises  a  direct  effect  in  increasing  the 
resistance  to  the  flow  of  blood  through  the  heart,  and  squeezes  out  the 
contained  blood  into  the  coronary  veins.  On  account  of  this  pumping 
action  of  the  muscular  walls  the  flow  of  blood  through  the  coronary 
system  is  greater  in  a  beating  heart  than  in  a  heart  which  is  quiescent. 

In  an  excised  heart  which  is  being  perfused  through  its  coronary  vessels  the 
rate  of  beat  of  the  heart  has  been  found  to  be  in  direct  proportion  to  the  pressure 
at  which  the  fluid  is  being  perfused.  This  is  the  case  even  when  the  fluid  is  non- 
nutritious,  such  as  liquid  paraffin  or  gum  solution,  and  has  therefore  been 
ascribed  to  a  direct  excitatory  effect  transmitted  from  the  coronary  vessels  to  the 
surrounding  heart-muscle.  The  influence  of  the  rate  of  beat  on  the  intra- 
coronary  pressure  is  shown  in  the  following  I'able  (Gutlirie  and  Pike) : 


Pressure  in 

Rate  of  beat 

mm.  Hg. 

po  1  minute 

90 

90 

140 

1.38 

156 

162 

175 

204 

104 

96 

Variation  in  pressure  —  94*4 

per  cent. 

Variation  in  rate  = 

126-6  per 

cent. 

^ 


This  statement  can  only  apply  to  cases  in  which  the  heart  is  being  insuffi- 
ciently fed.  In  a  heart  nourished  bj^  blood  and  doing  its  normal  work,  when  it  is 
entirely  cut  off  from  the  central  nervous  system,  the  rate  of  beat  is  unaltered  by 
changes  in  the  arterial  pressure.  This  can  be  sho^vn  very  easily  in  the  heart - 
lung  preparation  described  on  p.  1028.  In  fact,  under  such  conditions  the  rate  of 
the  heart-beat  depends  exclusively  on  tlie  temperature,  and  is  unaltered  by 
changes  in  arterial  jjressure,  venous  filling,  or  moderate  variations  in  the  gaseous 
contents  of  the  blood.  — -'  ^  ' 

Since  the  coronary  arteries  do  not  anastomose,  ligature  of  a  branch 
of  one  of  them  deprives  the  corresponding  part  of  the  heart-muscle  of  its 
blood-supply,  with  the  result  that  coagulation  necrosis  of  this  part 
sets  in.  If  the  branch  ligatured  be  a  large  one,  the  heart  very  often 
beats  for  one  or  two  minutes  with  unimpaired  force,  then  a  beat  is 
dropped  occasionally,  and  very  shortly  afterwards  the  heart  stops 
altogether  and  the  blood  pressure  falls  to  zero.  On  in.spoction  of 
the  heart  immediately'  after  the  blood  pressure  has  fallen,  its  mus- 
cular wall  is  seen  to  be  in  a  state  of  fibrillar  contractions,  or  '  delirium 
cordis.^  All  the  strands  of  muscle  fibres  are  contracting  more  cr 
less  rhythmically,  but  the  rhythms  of  no  two  parts  coincide,  so  that 
the  heart  dilutes  and  is  incapable  of  carrying  on  the  circulation.  It 
is  probably  in  this  way  that  sudden  deaths  occur  in  cases  where  the 


1086  PHYSIOLOGY 

coronary  arteries  are  diseased  or  calcified.  In  such  cases  a  man  may 
drop  down  dead,  having  previously  shown  no  symptoms  of  heart 
mischief. 

Delirium  cordis  may  be  explained  as  the  result  of  block,  produced 
by  interference  with  the  nutrition  of  a  large  part  of  the  heart- wall. 
The  contractile  wave  arri\dng  at  this  part,  in  some  directions  will  not 
spread  at  all,  in  others  will  spread  at  a  lower  rate,  so  that  different 
parts  of  the  heart  receive  the  impulse  to  contract  at  different  times 
and  a  state  of  inco-ordination  results.  The  same  condition  can  be 
produced  by  freezing  the  apex  of  the  ventricle,  so  causing  a  block, 
or  by  stimulating  the  surface  of  the  ventricle  at  a  rate  which  is  greater 
than  can  be  taken  up  by  the  ventricle  as  a  whole,  as,  e.g.,  by  tetanising 
currents.  Such  a  condition  in  the  higher  animals,  as  the  dog  and  man, 
is  practically  irrecoverable,  although  in  the  rabbit,  and  very  rarely 
in  the  dog.  it  is  sometimes  possible  to  bring  the  heart  back  to  a  state 
of  rhythmic  contraction  by  kneading  it  rhythmically. 


SECTION  IX 

THE  NERVOUS  REGULATION  OF  THE 

HEART 

In  order  that  the  activity  of  the  heart  may  be  adapted  to  the  needs 
oi  the  body  as  a  whole,  its  automatic  mechanism  must  be  subject  'o 
the  central  nervous  system,  which  must  be  able  to  affect  the  heart  n 
either  of  two  ways,  viz.  by  increasing  or  diminishing  the  cardiac  action. 
The  subjection  of  the  heart's  acti\'ity  to  the  integrative  action  tf 
the  central  nervous  system  is  also  necessary  for  the  sake  of  the  organ 
itself  ;  otherwise  the  peripheral  adaptation  of  the  heart-muscle  to 
changes  in  arterial  resistance  might  result  in  its  exhaustion  and  per- 
manent damage. 

The  regulation  is  effected  through  the  intermediation  of  afferent 
and  efferent  nerve  fibres  connecting  the  heart  with  the  central  nervous 
system.  The  importance  of  these  nerves  is  shown  by  the  behaviour  of 
animals  in  which  they  have  been  extirpated.  Thus  a  dog  in  whom  all 
the  nerves  of  the  heart  had  been  divided  survived  the  operation  for 
eight  months,  the  pulse  reading  during  the  time  not  having  appreciably 
altered  and  the  animal  being  in  a  fair  condition  of  health.  Although 
he  regained  his  normal  weight  after  the  operation,  he  was  found 
incapable  of  carrying  out  even  a  moderate  amount  of  work,  such  as 
that  represented  by  running,  since  the  mechanism  for  increasing  the 
action  of  the  heart  in  response  to  the  needs  of  the  muscles  had  been 
lost. 

THE  EFFERENT  CARDIAC  NERVES 

The  heart  in  vertebrates  is  supplied  with  nerve  fibres  from  two 
sources,  from  the  medulla  oblongata  along  the  vagus  nerves,  and  from 
the  upper  dorsal  region  of  the  spinal  cord  through  the  mediation  of  the 
sympathetic  system. 

The  fibres  which  run  through  the  sympathetic  system  take  a  some- 
what different  course  in  the  animals  on  which  the  regulation  of  the 
heart's  activity  has  been  chiefly  studied,  viz.  the  frog  and  the  mammal. 
In  the  frog  (Fig.  447)  the  sympathetic  fibres  leave  the  spinal  cord  by 
the  anterior  root  of  the  third  spinal  nerve  ;  they  then  pass  through 
the    white  ramus    comraunicans  to  the   corresponding  sympathetic 

1187 


1088  PHYSIOLOGY 

ganglion,  whence  they  run  up  through  the  second  gangHon  and 
the  annulus  of  Vieussens  to  the  first  ganghon  ;  they  then  pass 
into  the  cervical  sympathetic  strand  to  the  gafiglion  trunci  vagi ; 
here  they  join  the  vagus  and  pass  down  with  the  true  vagus  fibres 
to  the  heart. 

In  the  dog  (Fig.  448)  the  sympathetic  fibres  leave  the  spinal  cord  by 
the  anterior  roots  of  the  second  and  third  dorsal  nerves,  run  in  the 
white  rami  communicantes  to  the  stellate  ganglion,  and  thence  by  the 


_  ^Juq.  Ganql.  Vagus 


Vago-symparheh 

Subclav.  art  - 
N.lll 


Aorra 


N.VIII 

N.IX. 

Fig.  447.  Sympathetic  chain  of  frog  (right  side)  to  show  connection  with 
vagus  nerve.  The  sympathetic  ganglia  with  their  branches  are  black. 
Of  the  peripheral  branches  only  the  splanchnic  nerve  is  represented. 
(Modified  from  Ecker.) 

annulus  of  Vieussens  to  the  inferior  cervical  ganglion.  Cardiac 
branches  convey  the  sympathetic  fibres  to  the  heart  and  are  given  off 
from  the  stellate  gauglion,  the  inferior  cervical  ganglion,  and  from  the 
trunk  of  the  vagus. 

By  the  nicotine  method  it  is  possible  to  trace  out  the  cell  con- 
nections of  these  fibres.  As  they  leave  the  cord  they  are  m,edullated 
nerve  fibres,  similar  to  the  other  fibres  making  up  the  visceral  outflow 
throughout  the  dorsal  region  ;  the  white  fibres  pass  along  the  ramus 
communicans  to  the  stellate  ganglion,  where  they  end,  forming 
synapses  with  the  cells  of  the  ganglion.    Here  fresh  relays  of  fibres, 


THE  NERVOUS  REGULATION  OF  THE  HEART   1089 

which  are  non-medullated,  start  and  carry  the  impulses  to  the  heart 
along  the  various  cardiac  nerves  just  mentioned.  In  the  heart  these 
fibres  are  distributed  to  the  muscle  fibres  without  the  intervention 
of  any  other  ganglion-cells.  On  the  other  hand,  the  fibres  which  leave 
the  vagus  to  pass  to  the  heart  make  connection  with  the  cells  of 
Remak's  ganglion,  and  probably  all  the  other  intrinsic  cardiac  ganglia 


G.J. 


G.h.V- 


<J.Tli.4. 


Fig.  448.  Diagram  of  cardiac  inhibitory  and  accelerator  fibres  in 
the  dog.  (From  Foster.) 
r.Vg,  roots  of  the  vagus  ;  r.Sp.Ac,  roots  of  the  spinal  accessory  ;  GJ, 
ganglion  jug\ilarc  ;  G.h.V,  ganglion  trunci  vagi ;  Vg,  trunk  of  vagus  nerve  ; 
t'.Sy.  cervical  sympathetic  ;  C;C,  inferior  cervical  ganglion  ;  AV,  annulus  of 
Vieussens  ;  A.sb,  subclavian  artcrv  ;  nc,  cardiac  nerves  ;  G.St,  ganglion 
stellatum  ;  D2,  1)3.  ])4.  Do,  second,  third,  fourth,  and  fifth  dorsal  spuial 
roots  ;   G.Th,  ganglia  of  the  thoracic  chain. 

described  above,  whence  non-medullated  fibres  carry  their  impulses 
to  the  heart-muscle. 

ACTION  OF  THE  VAGUS 
The  action  of  the  vagus  fibres  on  the  heart  is  alm(»st  identical  in 
frog  and  mammal.     If  in  the  dog  the  peripheral  end  of  the  cut  vagus  be 
stimulated  while  the  arterial  blood  pressure  is  being  recorded  by 

69 


1090  PHYSIOLOGY 

means  of  a  mercurial  manometer,  the  pulse  is  seen  to  become  slower, 
or  with  a  stronger  stimulus  to  cease  altogether,  and  the  blood  pressure 
falls  towards  zero.  On  discontinuing  the  stimulus  the  heart  begins  to 
beat  again  and  the  pressure  rises  after  a  few  beats  to  normal  (Fig.  449). 
If  the  stimulation  of  the  vagus  be  prolonged,  the  blood  pressure, 
on  discontinuance  of  the  stimulus,  may  rise  above  normal  owing  to  the 
asphyxia  of  the  vaso-motor  centres  produced  by  the  prolonged  cessa- 
tion of  the  circulation.  Even  during  the  application  of  the  stimulus 
the  heart  often  begins  to  beat  again  with  a  slow  rhythm.  In  this  case 
we  speak  of  an  '  escape  '  of  the  heart  from  the  vagus  influence.  This 
escape  is  generally  confined  to  the  ventricles  and  the  heart-beats  are 
found  on  opening  the  chest  to  be  purely  ventricular,  the  auricles  and 
great  veins  remaining  in  a  state  of  diastole.  Vagus  escape  is  favoured 
by  distension  of  the  heart  cavities,  and  is  often  synchronous  -with  the 


Fig.  449.     Blood-pressure  tracing  from  carotid  of  dog  (taken  with  Hiirthle's 

manometer),  showing  effect  of  excitation  of  vagus  (between  the  arrows). 

o,  abscissa  line  of  no  pressure. 

respiratory  efforts,  which  supervene  after  a  certain  duration  of  inhibi- 
tion as  a  result  of  the  asphyxia  of  the  respiratory  centre. 

When  the  arterial  system  is  dilated,  so  that  the  mean  systemic 
pressure,  and  consequently  the  venous  pressure  during  cardiac  inhibi- 
tion, are  low,  or  when  the  asphyxial  gasps  of  the  animal  are  prevented 
by  anaesthesia  or  by  section  of  the  spinal  cord,  the  heart  may  fail  to 
recover  from  the  inhibition  produced  even  by  a  transitory  stimulation 
of  the  vagus.  In  such  cases  it  is  necessary  to  knead  the  heart  in  order 
to  restore  its  rhythmic  action. 

To  study  the  influence  of  the  vagus  on  the  auricles  and  ventricles 
respectively,  it  is  necessary  to  work  with  the  chest  opened  and  to 
record  separately  the  contractions  of  the  different  segments  of  the 
heart.  It  is  then  found  that  the  vagus  may  affect  the  heart  in  one  of 
several  ways.  Its  most  marked  action  is  on  that  part  of  the  heart 
where  it  enters,  viz.  the  venous  end.  It  may  affect  that  part  of  the 
auricle  corresponding  to  the  primitive  sinus  venosus,  where  the 
rhythm  of  the  whole  heart  is  determined.     In  this  case  the  sole  effect 


THE  NERVOUS  REGULATION  OF  THE  HEART      1091 

of  the  vajTus  on  the  auricles  and  ventricles  will  consist  in  an  alteration 
of  rhythm.  They  may  cease  to  beat  altogether  or  they  may  give  beats  of 
normal  strength  but  at  a  slower  rhythm  than  before.  Often  indeed 
under  these  conditions  the  beats  of  the  ventricles  may  be  increased 
in  size,  since  the  strength  and  extent  of  their  contractions  are  deter- 
mined, not  by  the  strength  of  the  stimulus  arriving  from  the  auricles, 
but  by  the  tension  to  which  their  fibres  are  exposed,  and  this  will 
increase  with  any  lengthening  of  the  diastolic  period,  and  consequent 
increased  diastolic  filling  of  the  ventricle. 

If  the  vagus  acts  on  the  auricles  without  affecting  the  sinus  part 
of  the  auricles  (sino-auricular  node),  the  rhythm  Avill  be  unaltered, 
but  the  response  of  the  auricles  to  the  impulses  received  by  them  VN-ill 
be  diminished,  and  the  amplitude  of  the  excursions  of  the  lever  attached 
to  them  will  therefore  be  considerably  reduced.  Indeed  the  auricular 
contractions  may  be  reduced  to  such  an  extent  that  they  cause  no 
movement  of  the  lever.  It  is  only  by  observing  their  surface  that  one 
may  perceive  a  slight  contraction  of  their  fibres.  Under  such  circum- 
stances the  rhythm  of  the  ventricles  will  be  unchanged. 

Generally  the  vagus  absolutely  stops  the  action  of  all  parts  of  the 
auricles  ;  in  such  cases  the  ventricles  also  cease  beating.  Very  often 
after  a  short  pause  the  ventricles  commence  to  beat  at  a  slow  rh\i:hm, 
and  it  is  then  seen  that  they  are  contracting  independently  of  the  auricles 
and  sinus.  That  the  ventricle  is  really  inaugurating  the  beat  is  shown 
by  the  fact  that  occasionally  one  may  observe  a  reversed  beat,  i.e.  a 
contraction  of  the  auricle  following  instead  of  preceding  each  ventri- 
cular contraction.  Whether  the  vagus  has  a  direct  action  on  the 
mammalian  ventricle  is  still  doubtful ;  its  effect  is  at  any  rate  very 
slight  as  compared  with  that  on  the  venous  end  of  the  heart.  The  fact 
that  stimulation  of  the  vagus  causes  as  a  rule  temporary  cessation  of 
the  ventricular  beat,  while  functional  separation  of  the  ventricles  from 
the  auricles  causes  no  such  temporary  stoppage,  would  seem  to  indicate 
that  this  nerve  has  a  direct,  though  slight,  action  on  the  ventricles. 

Finally  the  vagus  may  affect  the  tissue  which  conducts  the  excitatory 
process  from  one  cavity  to  another.  Under  vagus  stimulation  the 
auricles  may  beat  at  a  greater  rhythm  than  the  ventricles,  a  block 
havdng  been  produced  in  the  tissue  passing  from  auricles  to  ventricles, 
viz.  the  auriculo-ventricular  bundle. 

Engelmann  has  described  these  effects  of  vagus  excitation  as  negatively 
chronotropic  (diminution  of  riiythm),  negatively  inotropic  (diminished  strength  of 
contraction),  and  negatively  dromotropic  (diminislied  conductivity),  and  has 
distinguished  a  fourth  action,  viz.  one  on  the  irritability  of  the  muscle  to  direct 
stimuli,  which  ho  calls  negatively  hathmotropic.  He  ascribes  these  four  actions 
to  four  different  sets  of  nerve  fibres,  but  it  is  evident  that  they  arc  duo  not 
so  much  to  the  difference  in  the  nature  of  the  impulse  as  to  a  difference  in  the 
place  of  incidence  of  the  impulse. 


1092  PHYSIOLOGY 

Tlius,  if  the  vagus  fibres  which  are  distributed  to  the  remains  of  the  sinus  are 
specially  active,  we  shall  get  alterations  of  rhythm  affecting  the  whole  heart. 
If  those  which  supply  tlie  A-V-  bundle  are  excited,  the  most  pronounced  effect 
Avill  be  on  the  propagation  of  the  excitatory  process  from  auricles  to  ventricles. 

Practically  the  same  description  will  apply  to  the  action  of  the 
vagus  on  the  frog's  heart.  Since  it  is  easy  in  this  animal  to  register 
the  contractions  of  the  empty  heart  it  is  possible  to  show  that  the 
vagus  has  a  direct  inhibitory  action  on  the  ventricles,  diminishing  the 
strength  of  its  contraction  in  response  to  the  stimuli  transmitted  to  it 
from  the  venous  end.  This  action  of  the  vagus  on  the  ventricle  is  not, 
however,  universal,  and  in  the  tortoise  it  is  impossible  to  show  any 
such  action.  In  both  these  animals  the  auricles  show  the  same  effects 
as  in  the  mammal,  viz.  an  influence  limited  to  the  rhythm  when  only 
the  sinus  is  affected,  or  a  diminution  of  the  strength  of  contraction 
when  the  sinus  is  unaffected  and  the  chief  action  of  the  vagus  is  on 
the  auricular  muscle. 

Ever  since  the  discovery  in  1845  by  the  brothers  E.  H.  and  E.  F. 
Weber  of  the  action  of  the  vagus  on  the  heart,  much  work  has  been 
expended  with  a  view  to  determining  the  intimate  nature  of  the 
inhibitory  process.  In  the  former  neurogenic  theory  it  was  supposed 
that  the  vagus  altered  the  activity,  perhaps  by  a  process  of  '  inter- 
ference,' of  the  ganglion-cells  responsible  for  the  origination  of  the 
rhythm.  Many  facts,  however,  point  to  the  inhibitory  impulses  as 
being  continued  to  the  heart-muscle  itself.  Thus  tetanisation  of  any 
portion  of  the  frog's  ventricle,  especially  if  it  be  filled  with  blood, 
causes  an  evident  relaxation  of  the  part  between  the  electrodes. 
Application  of  nicotine  to  the  heart  prevents  stimulation  of  the  trunk 
of  the  vagus  from  having  any  influence  on  the  heart,  presumably  from 
paralysis  of  the  cells  of  Remak's  ganglion,  which  lie  at  the  termina- 
tion of  the  vagus  fibres,  or  of  the  synapses  between  the  vagus  fibres 
and  the  ganglion- cells.  It  is  still  possible  to  inhibit  the  heart  by 
direct  stimulation  either  of  the  fibres  leaving  this  ganglion  in  the  sino- 
auricular  junction,  or  of  the  nerve-trunks  which  run  in  the  inter- 
auricular  septum.  We  must  conclude  therefore  that  the  inhibition  of 
the  heart-muscle  is  peripheral  and  depends  on  the  direct  action  of  the 
nerve  fibres  on  the  muscle-cells  themselves.  These  nerve  fibres  are 
paralysed  by  atropine,  after  administration  of  which  no  inhibitory 
effects  can  be  produced  by  stimulation  of  nerve  or  muscle  or  any 
part  of  the  heart.  On  the  other  hand,  muscarine  apparently  stimu- 
lates the  inhibitory  nerve-endings,  and  when  applied  to  the  isolated 
auricle  or  ventricle  causes  weakening  of  the  beat  and  finally  com- 
plete inhibition,  an  effect  which  can  be  removed  by  its  antagonist 
atropine. 

Two  views  have  been  held  as  to   the   essential  nature   of  the 


THE  NERVOUS  REGULATION  OF  THE  HEART      1093 

inhibitory  process.  According  to  that  put  forward  by  Claude  Bernard, 
the  natural  tendency  of  any  tissue  during  rest  is  towards  anabolism. 
Activity  involves  disintegration  or  breakinfr  down  of  the  living  material, 
and  this  disintegration  must  be  succeeded  by  a  process  of  building  up 
or  anabolism,  which  restores  the  tissue  to  its  previous  functional  con- 
dition. On  this  view  the  state  of  inhibition  would  merely  prolong  the 
period  of  rest  intervening  between  two  periods  of  activity,  so  allowing 
a  greater  time  for  restitution  to  take  place,  with  a  corresponding 
improvement  in  the  functional  capacity  of  the  tissue.  According  to 
Hering  and  Graskell  a  state  of  anabolism  can  be  induced  in  a  tissue  com- 
parable to  the  state  of  sudden  disintegration  which  is  associated  with 
activity.  Excitation  of  the  vagus  nerve  does  not  merely  allow  the 
normal  process  of  building  up,  which  goes  on  during  rest,  to  take  place, 
but  actually  hastens  these  processes,  just  as  the  excitation  of  a  moter 
nerve  to  a  skeletal  muscle  induces  an  active  breakdown  of  the  con- 
tractile tissue,  or  the  excitation  of  the  augmentor  nerve  to  the  heart 
induces  an  increased  rate  of  beat  and  therefore  increased  functional 
activity. 

If  stimulation  of  an  inhibitory  nerve  induces  the  opposite  chemical 
change  to  that  occurring  during  activity,  one  would  expect  to  find 
that,  just  as  an  active  part  of  a  tissue  is  negative  to  an  inactive  part, 
so  a  part  of  the  tissue  which  is  under  the  influence  of  an  inhibitory 
stimulus  should  be  electio-positive  to  any  part  which  is  not  being  so 
stimulated.  According  to  Gaskell  this  condition  is  realised  in  the  heart 
of  the  tortoise.  The  auricles  are  brought  to  a  standstill  by  separating 
them  from  the  sinus  venosus.  The  apex  of  one  auricle  is  then  injured  by 
heat,  and  the  injured  point  and  uninjured  base  are  led  off  to  a  galvano- 
meter. The  usual  demarcation  current  dependent  on  the  difference 
of  potential  between  the  injui-ed  and  uninjured  portion  is  thus 
observed.  If  the  vagus  be  now  stimulated  the  auricles  remain  at  rest, 
but  the  demarcation  current  is  increased,  i.e.  a  positive  variation  is 
produced,  an  electrical  condition  opposed  in  sign  to  that  which  would 
take  place  when  the  auricles  contract.  Doubt  still  exists,  however,  as 
to  the  exact  interpretation  to  be  put  on  this  experiment. 

It  was  mentioned  above  that  potassium  salts  promote  relaxation  of  the 
ventricle,  so  acting  as  antagonists  to  calcium  salts.  If  potassium  salts  be  present 
in  a  sufficient  concentration  in  the  circulating  fluid,  the  heart  is  brought  to  a 
standstill  in  a  condition  of  diastole,  as  if  the  vagus  mechanism  were  inactive. 
On  removal  of  the  excess  of  K'  ions  the  heart  at  once  starts  beating  again.  Howell 
has  shoAvn  that  during  stimulation  of  the  vagus  the  amount  of  potassium  in  a 
diffusible  form  in  the  heart-mu.scle  is  increased.  He  has  therefore  suggested  that 
the  action  of  the  vagus  in  stopping  the  heart  is  effected  by  the  liberation  of 
potassium  salts.  Potassium  normally  exists  in  a  large  percentage  in  the  heart- 
muscle,  but  in  a  combined  form,  and  Howell  assumes  that  stimulation  of  the 
vagus  effects  a  dissociation  of  tliis  combined  putaf^.sium.  so  that  the  liberated  ions 
are  able  to  exert  their  inliibitory  influence  on  the  heart. 


1094 


PHYSIOLOGY 


THE  TONIC  ACTION  OF  THE  VAGUS 
If  both  vagi  of  a  mammal  be  divided,  the  lieart  as  a  rule  beats  more 
frequently,  showing  that  under  normal  circumstances  tonic  impulses 
are  constantly  descending  the  vagi  and  holding  the  heart's  action  in 
check.  The  extent  of  the  quickening  which  is  produced  by  section 
of  the  vagi  varies  in  different  animals  and  is  apparently  associated  with 
the  conditions  of  life  of  the  animal  and  its  powers  of  carrying  out  pro- 
longed muscular  exertions.  Thus  in  the  dog  or  horse  the  pulse, 
which  is  normally  slow,  may  be  doubled  in  frequency  by  section  of  the 
vagi.  In  the  rabbit,  which  has  a  frequent  pulse,  and  is  only  able  to 
run  for  a  short  distance,  division  of  both  vagi  causes  very  little  altera- 
tion in  the  pulse-rate.  It  is  stated  that  the  tonic  action  of  the  vagi  is 
much  greater  in  the  hare  than  in  the  rabbit. 

This  tonic  action  may  be  increased  by  various  conditions  of  the 
blood,  e.g.  the  presence  of  drugs,  such  as  morphia. 


Fig.  450.     Tracings  of  ventricular  (upper  curve)  and  auricular 

contractions  (lower  curve). 

From  xto  y  the  accelerator  nerves  stimulated.     Lowest  line  =  seconds. 


ACTION  OF  THE  SYMPATHETIC  CARDIAC  NERVES 
Stimulation  of  the  sympathetic  cardiac  nerves  at  any  part  of  their 
course  has  an  effect  on  the  heart  the  exact  reverse  of  that  produced  by 
stimulating  the  vagi.  In  most  cases  the  pulse  frequency  is  increased 
in  consequence  of  the  action  of  these  nerves  on  that  part  of  the  heart 
from  which  the  rhythm  starts.  The  frequency  which  is  attained  by 
maximal  stimulation  of  the  accelerator  nerves  is  independent  of  the 
previous  rate  of  the  heart-beat.  The  increase  in  rate  involves  a  shorten- 
ing of  the  time  of  the  cardiac  cycle,  which  chiefly  affects  the  diastolic 
period.  The  size  of  the  auricular  and  ventricular  contractions  may  be 
increased  at  the  same  time  as  their  rate.  In  fact,  like  the  vagus  nerves, 
the  sympathetic  fibres  of  the  heart  can  influence  either  rhythm  or 
strength  of  contraction,  or  the  conduction  from  auricle  to  ventricle, 
according  to  the  part  of  the  heart-muscle  which  is  affected. 

The  augmentor  effect  on  the  strength  of  the  ventricular  beats  is 
often  very  marked.  The  sympathetic  fibres  are  much  less  easily  tired 
than  the  vagus  fibres,  and  have  a  longer  latent  period.     Whereas  the 


THE  NERVOUS  REGULATION  OF  THE  HEART   1095 

latent  period  of  the  vagus  in  the  mammal  is  considerably  less  than  one 
second,  that  of  the  accelerator  nerves  may  amount  to  ten  or  even 
twenty  seconds  (Fiji;.  450).  Hoiicc  if  the  vauo-.syinpathotic  of  the  frog  be 
stimulated,  the  first  effect  is  inhibition  due  to  vagus  actioji.  The  vagus 
nerve-endings  then  become  fatigued,  and  the  influence  of  the  accelera- 
tor fibres  makes  itself  apparent,  and  the  heart  commences  to  beat,  and 
the  beats  become  more  rapid  and  forcible  than  before  (Figs.  451,  452). 


'•;-^W 


TfPflf^yfP^(Ymvml^mwYYTTYm^ 


iiii 


;j;,,W,»**lii!iiiillil 


Fig.  451.  Tracing  to  show  effect  of  stimulation  of  the  vago-syiupathetic  nerve 
on  the  frog's  heart.  The  rhythm  is  unaltered,  but  the  beats  of  auricle  and 
ventricle  are  much  decreased  in  size.  On  ceasing  the  stimulation  the  beats 
become  augmented.     (Gaskell.) 


Fig.  4.52.  A  tracing  similar  to  Fig.  i'yl.  In  this  case,  however,  the  stimulation 
caused  complete  stoppage  (inhibition)  of  both  auricular  and  ventricular 
beats.     (Gaskell.) 

Like  the  vagus,  the  sympathetic  nerve  fibres  appear  to  exercise  a 
tonic  influence  on  the  heart,  so  that  after  extirpation  of  the  stellate 
ganglion  on  each  side,  the  pulse  frequently  becomes  permanently 
slowed. 

THE  HEART   REFLEXES 

The  part  of  the  nervous  system  chiefly  concerned  in  tiie  central 
co-ordination  of  the  various  afferent  impulses  which  act  on  the  heart  is 
the  medulla  oblongata.  It  is  in  this  situation  that  we  find  the  nerve- 
cells  giving  origin  to  the  efferent  fibres  of  the  vagus  nerves,  and  also 
the  collection  of  grey  matter  in  which  the  afferent  fibres  of  the  vagus 
terminate.  Direct  stimulation  of  the  vagus  centre  nuiy  cause  slowing 
and  stoppage  of  the  heart.     The  tonic  influence  of  the  vagi  can  be 


1096 


PHYSIOLOGY 


abolished  by  destruction  of  this  centre.  In  this  region  we  also  find  the 
vaso-motor  centre,  so  that  the  activity  of  one  can  affect  that  of  the 
other.  This  cardiac  centre  may  be  played  upon  by  impulses  arriving  at 
it  through  various  afferent  nerves  or  from  the  higher  parts  of  the  brain 
and  giving  rise  to  the  changes  of  the  pulse-rate  associated  with  the  emo- 
tional conditions,  or  it  may  be  directly  affected  by  the  composition  of 
the  blood  circulating  through  its  capillaries. 

The  nerve-cells  which  give  off  the  accelerator  or  augmentor  fibres 
are  situated  in  the  intermedio-lateral  tract  of  the  spinal  cord,  near 
the  point  of  origin  of  these  fibres.  We  might  therefore  speak  of  an 
augmentor  centre  in  this  region  ;    but  it  seems  probable  that  the 


Sup-,  lar.  n.    - 


Depressor 


I 


-sec. 


—  Symp. 


-Vaqus 


Vagus 


Sup-,  lar.  n.- 


RABBIT 


-  Sup-.  Cerv.  Gang. 
Depressor 
--Cerv.  symp.  n. 


Vago.  symp. 


DOG 


Fig.  453.  Diagrams  of  the  connections  of  the  depressor  nerve  in  the  rabbit  and 
dog,  according  to  Cyon.  It  will  be  noticed  that  in  the  latter  animal  the 
depressor  nerve  runs  in  the  vagus  trunk  for  the  greater  part  of  its  course. 


activity  of  these  cells  is  subordinate  to  impulses  arriving  at  them  from 
the  common  meeting-place  of  visceral  impulses,  viz.  the  medulla. 

The  most  important  of  the  afferent  nerves  which  affect  reflexly  the 
action  of  the  heart  are  the  nerves  coming  from  the  heart  itself  and  the 
aorta.  In  the  mammalian  ventricle  nerve  fibres  can  be  seen  running 
over  the  surface  of  the  ventricle  which  are  entirely  afferent,  stimulation 
of  their  peripheral  ends  causing  no  effect  on  the  heart-beat.  Stimula- 
tion of  their  central  ends  may  cause  one  of  four  conditions  : 

(a)  Slowing  of  the  heart. 

(6)  Kise  of  blood  pressure  from  constriction  of  the  splanchnic 
area. 

(c)  Fall  of  blood  pressure  by  dilatation  of  the  arterioles  of  the 
body. 

{d)  Reflex  movements.     The  heart  does  not  seem  to  be  provided 


THE  NERVOUS  REGULATION  OF  THE  HEART   1097 

with  the  nerves  of  ordinary  or  tactile  sensibility.  There  is  no  doubt, 
however,  that  under  abnormal  circumstances  impulses  arising  in  the 
heart  can  give  rise  to  sensations  of  pain  which  are  referred  not  so  much 
to  the  heart  as  to  the  surface  of  the  body  over  the  left  side  of  the  chest 
and  left  arm,  in  the  region  of  the  distribution  of  the  cutaneous  branches 
of  the  second  and  third  dorsal  roots. 

An  important  afferent  nerve  coming  from  the  heart,  or  rather 
from  the  beginning  of  the  aorta,  is  the  depressor  nerve.  In  the  rabbit 
this  rises  by  two  roots,  one  from  the  trunk  and  the  other  from  the 


Fig.  454.     Blood-pressuio  curve  from  rabbit  showing  effect  of  excitation  of  central 
end  of  depressor  nerve  (mercurial  manometer).     (Bavliss.) 


superior  laryngeal  branch  of  the  vagus,  and  runs  parallel  with  the  vagus 
to  the  cardiac  plexus  (Fig.  453).  It  is  purely  afferent,  stimulation  of  its 
peripheral  end  causing  no  effect.  On  stimulating  its  central  end  fall  of 
blood  pressure  (Fig.  454)  and  reflex  slowing  of  the  heart  are  produced, 
the  latter  effect  being  abolished  by  section  of  both  vagi.  It  has  been 
shown  by  Bayliss  that  the  depressor  effect  is  due  to  universal  dilata- 
tion of  the  blood-vessels  of  the  body,  the  greater  part,  however,  being 
played  by  the  splanchnic  area.  This  nerve  is  probably  brought  into 
action  whenever  the  pressure  in  the  aorta  is  so  high  as  to  constitute 
a  serious  check  to  the  expulsive  action  of  the  heart.  It  is  stated  that 
under  these  conditions  a  current  of  action  may  be  detected  in  the 
trunk  of  the  depressor  nerve,  and  that  if  both  depressor  nerves  be 
cut  when  the  aortic  pressure  is  high  the  blood  pressure  rises  still 
higher.     It  presents  a  means  by  which  the  heart  can  be  relieved  of 


1098  PHYSIOLOGY 

a  load  too  great  for  its  powers,  and  therefore  dangerous  to  its  future 
welfare.  In  many  animals  the  depressor  fibres  are  bound  up  with 
the  trunk  of  the  vagus  and  cannot  be  excited  separately. 

Stimulation  of  the  central  end  of  the  vagus  generally  causes  reflex 
slowing  of  the  heart  through  the  cardiac  centre  and  the  other  vagus. 
In  this  reflex  inhibition  the  chief  fibres  stimulated  are  those  coming 
from  the  lungs  (Brodie).  Inflation  of  the  lungs  causes  acceleration  of 
the  heart — whether  due  to  diminution  of  the  tonic  action  of  the  vagi, 
or  to  reflex  excitation  of  the  accelerator  nerves,  is  not  known. 
Most  sensory  nerves  of  the  body  when  stimulated  give  either  a  slowing 
or  a  quickening  of  the  heart.  Stimulation  of  the  fifth  nerve,  as  in  the 
nasal  mucous  membrane,  always  causes  reflex  inhibition. 

The  rate  of  the  heart-beat  in  the  normal  animal  is  closely  connected 
with  the  blood  pressure.  Increase  in  blood  pressure  due  to  a  large 
vaso-constriction  is  associated  as  a  rule  (but  not  invariably)  with  a 
slowing  of  the  heart-beat.  In  fact,  '  Marey's  law  '  states  that  the  fulse- 
rate  varies  inversely  as  the  blood  pressure.  In  this  slowing  of  the  heart 
the  vagus  nerves  are  of  course  active.  Whether  the  blood  pressure  acts 
directly  on  the  cardiac  centre  in  the  medulla,  or  reflexly  through  afferent 
nerves  distributed  to  the  aorta  and  heart  cavities,  is  not  yet  fully  made 
out.  The  reflex  slowing  of  the  heart  often  fails  to  accompany  rise  of 
blood  pressure.  Thus  the  rise  in  blood  pressure  and  the  increased 
filling  of  the  heart  associated  with  muscular  exercise  are  attended  by  an 
increased  pulse-rate. 

THE  PULSE-RATE  IN  MAN 

The  normal  pulse-rate  in  man  is  about  72  per  minute.  It  is  largely 
influenced  by  bodily  movements.  The  pulse-rate  varies  considerably 
with  age.  The  following  Table  represents  the  average  pulse-rate  in 
man  at  difierent  ages  : 

Pulse-rate 

Age  in  years  per  minute 

0  ..  136 

5       •  ..  88 

10-15  . .  78 

15-60  . .  68-72 

It  must  be  remembered  that  marked  differences  in  pulse-rate 
may  be  found  in  different  individuals  without  having  any  patho- 
logical significance.  Thus  pulse-rates  of  30  per  minute  and  120  per 
minute  have  been  observed  in  men  who  were  otherwise  perfectly 
healthy.  The  pulse-rate  is  raised  by  warmth  and  diminished  by 
cold  applied  to  the  surface  of  the  skin.  It  is  also  increased  some- 
what by  the  taking  of  food.  The  act  of  swallowing  causes  a  reflex 
quickening  of  the  rate  through  the  vagi. 


SECTION  X 


THE  EFFECT  OF  MUSCULAR  EXERCISE  ON 
THE  CIRCULATION 

Any  muscular  exercise,  even  moderate,  produces  rise  of  blood 
pressure  and  acceleration  of  the  pulse,  associated  vnih  an  increase  of 
pulmonary  ventilation — hyperpnoea.  These  effects  can  be  readily 
shown  by  running  up  and  do^\^^  stairs  for  half  a  minute.  The  following 
Table  by  Pembrey  and  Todd  shows  the  effect  of  such  a  form  of  exercise 
on  the  pulse-rate  and  systolic  blood  pressure  in  two  individuals,  one 
trained  and  the  other  untrained  : 


A.B.  (trained)                                   A.H.T.  (untrained) 

Rest 

Just  after 
exercise 

5  min.     '       „    ^ 
later      '      ^''"^ 

Just  after 
exercise 

5  min. 
later 

1.  B.P.  mm.  Hg.    . 

Pulse  I  min. 

2.  B.P.  mm.  Hg.     . 
Pulse  ^  min. 

110 

13 

122 

16 

134 
28 

134 
29 

1 
118            104 

14     :        18 
126           110 

17             23 

134 

27 

140 

30 

IDS 

24 

106 

26 

Several  factors  may  concur  in  the  production  of  these  effects.  In- 
creased contractions  of  voluntary  muscles  will  in  the  first  place  quicken 
the  return  of  venous  blood  to  the  heart,  and  so  will  cause  a  greater  dias- 
tolic distension  of  this  organ  and  therefore  a  greater  output  of  blood 
by  the  left  ventricle.  The  increased  respiratory  movements  will  also 
aid  the  venous  circulation  and  have  a  similar  effect  in  increasing  the 
systolic  output.  Moreover  the  increased  exercise  will  raise  the  tension 
of  carbonic  acid  in  the  blood  in  consequence  of  the  increased  produc- 
tion of  this  gas  by  the  contracting  muscles.  If  the  exercise  is  very 
violent,  lactic  acid  may  be  also  present  in  the  circulating  blood.  We 
have  already  seen  that  a  moderate  increase  in  the  H  ions  in  the  blood, 
whether  due  to  carbonic  acid  or  lactic  acid,  gives  rise  to  increased 
diastohc  relaxation  of  the  ventricles  and  raises  its  output  into  the 
arteries.  All  these  factors  will  thus  concur  in  producing  a  rise  of 
pressure  even  when  the  heart  and  blood-vessels  are  cut  off  from  the 
central  nervous  system.  The  latter  also  is  concerned  in  the  rise 
of  pressure.     The  mere  act  of  attention  preparatory  to  muscular  effort 

1099 


1100 


PHYSIOLOGY 


is  in  itself  sufficient  to  raise  the  blood-pressure,  and  it  seems  probable 
that  the  increased  activity  of  the  motor  centres  actually  spreads  to  the 
medullary  centres  which  preside  over  the  heart  and  blood-vessels, 
and  that  there  is  an  active  constriction  of  the  vessels,  especially  of  the 
splanchnic  area,  so  that  the  greater  part  of  the  blood  in  circulation 
is  available  for  the  use  of  the  actively  contracting  muscles.  On  this 
account  hard  exercise  is  not  easily  carried  out  after  a  meal,  and,  if 
forced,  seriously  interferes  with  digestion,  by  the  diversion  of  the 

current  of  blood  needed  for  the  carry- 
ing out  of  this  function. 

Increase  of  carbonic  or  lactic  acid 
in  the  blood  will  afEect  the  vaso-motor 
centre  directly,  as  Mathison  has  shown, 
and  therefore  will  concur  in  causing  a 
rise  of  blood  pressure.  Since  the  blood 
vessels  of  a  contracting  muscle  are 
probably  dilated,  all  the  conditions 
are  present  for  maintaining  as  rapid  a 
flow  as  possible  through  the  parts 
which  are  the  seat  of  the  most  active 
metabolism. 

In  the  quickening  of  the  pulse-rate 
the  most  important  factor  is  probably 
the  central  nervous  system,  i.e.  the 
cardiac  centres  in  the  medulla  and 
upper  part  of  the  spinal  cord.  The 
acceleration  is  partly  central,  by  a 
spread  of  excitatory  impulses  from 
the  motor  paths,  partly  reflex  from  the 
heart,  the  afferent  impulses  resulting 
from  the  increased  tension  in  the  heart 
cavities  being,  so  to  speak,  switched 
off  from  the  cardio-inhibitory  on  to 
the  accelerator  centre.  Under  normal 
circumstances,  it  will  be  remembered, 
a  rise  of  blood  pressure  is  attended 
with  a  slowing  of  the  pulse.  In 
exercise  the  rise  of  blood  pressure  is  attended  with  cardiac  accelera- 
tion. Slight  acceleration  of  the  heart  is  observed,  after  division  of 
all  its  nervous  connections,  on  tetanising  the  lower  limbs.  Mansfeld 
has  shown  that  probably  the  chief,  if  not  the  only,  factor  in 
this  case  is  the  rise  of  temperature  in  the  blood  flowing  to 
the  heart.  When  exercise  is  discontinued  the  pulse-rate  and 
blood  pressure  rapidly  fall  to  normal,  the  return  being  quicker  in 


Fig.  455.  Curves  showing  the  in- 
fluence of  exercise  on  the  circula- 
tion. The  exercise  was  a  six-mile 
run.  Ordinates  =  mm.  Hg  pres- 
sure and  rate  per  minute.     (0.  S. 

LOWSLEY.) 


EFFECT  OF  EXERCISE  ON  CIRCULATION  1101 

the  case  of  a  trained  individual,  as  is    seen   in  the   Table  quoted 
above. 

SECOND  WIND.  It  is  a  familiar  experience  that  in  a  running 
race  of  any  duration  the  competitors  after  some  time  become  less 
distressed  than  at  the  commencement  of  the  race.  The  runner  is 
now  said  to  have  got  his  '  second  wind,'  and  can  continue  running 
with  apparent  comfort.  There  are  several  factors  which  may  account 
for  this  accommodation.  In  the  first  place,  as  a  result  of  the  produc- 
tion of  metabolites  in  the  contracting  muscles,  their  vessels  may  be 


FiG.  4.')().     Curvf  .sliowing  the  flfect  of  a  sudden  rise  in  the  arterial  resistance  on 
the  output  and  volume  of  the  ventricles.     Systole  causes  a  downward  move- 
ment of  the  lever. 
H,  heart  volume  ;    bp,  arterial  blood  pressure  ;    s,  signal  showing  duration 
of  stimulation  of  splanchnic  nerve  ;   T,  time-marker,  10  sees. 

more  dilated,  so  that  the  flow  of  blood  through  them  is  easier.  More 
important  is  the  change  in  the  heart  accompanying  the  onset  of 
second  wind.  As  Pembrey  and  Cook  have  shown,  the  onset  of  second 
wind  is  always  attended  with  a  diminution  in  the  pulse-rate.  At  the 
same  time  there  is  an  alteration  in  the  respiratory  quotient.  During 
distress  the  respiratory  quotient  is  high,  i.e.  more  carbon  dioxide  is 
being  given  out  than  oxygen  taken  in.  As  the  distress  diminishes, 
the  respiratory  quotient  also  falls.  The  improved  action  of  the  heart 
may  be  partly  due  to  the  increased  coronary  circulation,  since  a 


1102  PHYSIOLOGY 

similar,  though  more  rapid,  accommodation  of  this  organ  is  to  be  seen 
whenever  there  is  a  sudden  rise  of  blood  pressure.  Thus  if  the  pressure 
be  quickly  raised  by  clamping  the  descending  aorta  or  by  stimulation 
of  the  splanchnic  nerves,  the  ventricles  at  first  dilate,  so  that  their 
systolic  volume  increases  for  a  little  time,  while  the  blood  pressure  is 
rising.  As  a  result  the  blood  pressure  ceases  to  rise,  but  at  this  point 
the  ventricle  muscle  seems  to  gather  renewed  strength,  the  systohc 
volume  diminishes,  and  the  output  at  each  beat  increases,  so  that 
the  blood  pressure  rises  still  further  and  the  heart  continues  to  contract 
at  the  higher  level  of  blood-pressure  as  efficiently  as  it  did  before  the 
pressure  began  to  rise.  On  this  account  the  curve  of  blood  pressure 
is  generally  '  stepped.'  Such  a  curve  with  the  accompanying  changes 
in  the  heart  volume  is  shown  in  Fig.  456. 


SECTION  XI 

THE  NERVOUS  CONTROL  OF  THE  BLOOD- 
VESSELS 

During  muscular  activity  the  metabolism  of  the  body  as  a  whole, 
as  judged  by  its  gaseous  interchanges,  may  be  increased  six-  or  eight- 
fold. This  increase  is  due  almost  exclusively  to  the  additional  meta- 
bolic changes  consequent  on  muscular  activity.  The  muscles  there- 
fore during  activity  require  a  greater  supply  of  blood  in  order  to 
obtain  from  it  the  oxygen  necessary  for  their  contraction,  and  to 
get  rid  of  the  carbon  dioxide,  which  is  the  end- result  of  their  activity. 
In  the  same  way  every  organ  of  the  body  requires  an  increased 
blood-supply  during  activity.  Blood  must  be  diverted  from  the 
inactive  to  the  active  tissues.  All  parts  of  the  body  must  co-operate 
in  subordination  to  the  activity  of  that  tissue  whose  function  for  the 
time  being  is  of  the  greatest  importance  to  the  organism.  This  sub- 
ordination of  the  part  to  the  whole,  i.e.  of  every  part  to  the  organ 
whose  activity  is  specially  evoked  by  the  needs  of  the  whole  organism^ 
is  chiefly  effected  through  the  central  nervous  system,  though  local  and 
chemical  mechanisms  may  also  play  some  part  in  the  process. 

Our  knowledge  of  the  nervous  control  of  the  blood-vessels  dates 
from  the  discovery  by  Claude  Bernard  that  nerve  fibres  run  in  the 
cervical  sympathetic  to  the  blood-vessels  of  the  head  and  neck,  and 
maintain  them  in  a  state  of  tonic  constriction.  Bernard  showed  that 
if  in  the  rabbit  the  cervical  sympathetic  on  one  side  be  divided,  the 
vessels  in  the  corresponding  ear  dilate.  Vessels  come  into  prominence 
which  were  previously  invisible,  and  on  account  of  the  greater  flow 
of  blood  thus  produced,  the  ear  on  the  side  of  the  section  becomes 
warmer  than  the  normal  ear.  If  the  head  end  of  the  divided  sympa- 
thetic nerve  be  stimulated,  all  the  vessels  of  the  ear  contract,  and  the 
ear  becomes  colder  than  that  of  the  other  side.  The  fact  that  the 
dilatation  of  the  vessels  is  produced  by  section  of  the  cervical  sympa- 
thetic and  lasts  for  a  considerable  time  after  any  irritant  effect  of  the 
section  must  have  passed  off  shows  that  the  ear-vessels  are  con- 
tinuaUy  under  the  influence  of  tonic  constrictor  impulses  proceeding 
to  them  along  the  nerve  fibres  of  the  cervical  sympathetic. 

It  can  be  easily  shown  that  these  inijiulses  take  their  origin  in  the 
central  nervous  system.     The  paralysis  of  the   oar-vessels,   though 

1103 


1104  PHYSIOLOGY 

lessening  the  resistance  to  the  flow  of  blood  there,  affects  too  small 
a  vascular  area  to  have  any  marked  influence  on  the  total  resistance 
of  the  circulation  and  therefore  on  the  arterial  blood  pressure.  If  the 
spinal  cord  be  divided  on  a  level  with  the  region  of  the  first  dorsal 
nerve,  the  blood  pressure  sinks  considerably.  In  the  dog  it  may  fall 
from  120  mm.  Hg.  to  40  or  50  mm.  Hg.  The  heart  after  the  section 
beats  more  rapidly  than  before,  so  that  the  fall  of  pressure  must  be 
ascribed  to  a  change  affecting  the  blood-vessels  and  lowering  the 
resistance  to  the  flow  of  blood.  Since  a  maximal  effect  on  the  blood 
pressure  is  produced  by  section  of  the  cord  at  this  level,  one  may 
conclude  that  the  tonic  constrictor  impulses  to  all  the  vessels  of  the 
body  pass  through  this  segment  of  the  cord  before  leaving  it  to  be 
distributed  to  the  arterial  walls.  The  source  of  these  impulses  may 
be  made  out  by  studying  the  effect  of  sections  through  different  levels 
of  the  nervous  system.  Division  of  the  cord  at  about  the  first  or 
second  lumbar  nerve  causes  no  effect  on  the  blood  pressure.  On  making 
a  section  at  the  sixth  dorsal  root  a  considerable  fall  of  pressure  is  pro- 
duced, almost,  but  not  quite,  as  great  as  that  observed  after  section  at 
the  first  dorsal  segment ;  stimulation  of  the  lower  end  of  the  cut  cord 
causes  almost  universal  vascular  constriction  and  a  large  rise  of  blood 
pressure.  On  the  other  hand,  the  fall  of  pressure  is  maximal  when  the 
section  is  carried  through  the  first  dorsal  segment  or  through  any  part 
of  the  cervical  cord.  Section  of  the  crura  cerebri,  or  of  the  brain-stem 
at  the  upper  border  of  the  fourth  ventricle,  leaves  the  blood  pressure 
unaffected.  Destruction  of  a  small  region  of  the  medulla  situated  on 
each  side  of  the  middle  line  in  the  neighbourhood  of  the  facial  nucleus, 
i.e.  in  the  forward  prolongation  of  the  lateral  columns  after  they  have 
given  off  their  fibres  to  the  decussating  pyramids,  causes  an  immediate 
and  maximal  lowering  of  the  blood  pressure. 

We  must  therefore  conclude  that  all  the  vessels  in  the  body  are 
kept  in  a  state  of  tonic  contraction  by  impulses  arising  in  this  portion 
of  the  medulla  oblongata,  travelling  down  the  cord  as  far  as  the  dorsal 
region,  and  then  passing  out  of  the  cord  by  the  dorsal  and  upper 
lumbar  nerves.  This  conclusion  is  confirmed  by  the  fact  that,  whereas 
stimulation  of  the  anterior  roots  of  the  cervical  and  lower  lumbar 
and  sacral  nerves  has  no  influence  on  the  blood  pressure,  a  rise  of 
arterial  pressure  can  be  obtained  by  stimulating  any  of  the  anterior 
roots  from  the  first  or  second  dorsal  to  the  second  or  third  lumbar. 
The  same  effect  is  produced  by  stimulation  of  the  white  rami  com- 
municantes  from  these  roots  to  the  sympathetic  system,  or  by  excita- 
tion of  the  sympathetic  system  itself. 

The  portion  of  the  medulla  concerned  with  the  sending  out  of  the 
tonic  vaso-constrictor  impulses  is  spoken  of  as  the  vaso-motor  centre. 
In  this  region  it  is  exposed  to  and  played  upon  by  afferent  impulses 


NERVOUS  CONTROL  OF  THE  BLOOD-VESSELS      1105 

from  all  portions  of  the  body,  from  the  hijiher  centres  of  the  brain 
and  the  cortex  cerebri,  and  especially  by  afferent  impulses  travelling 
by  the  vagi  from  the  viscera  of  the  chest  and  abdomen.  Whether 
in  the  absence  of  all  afferent  stimuli  the  centre  would  be  active  is 
doubtful ;  all  we  know  is  that  the  sum  of  the  stimuli  arriving  at  the 
centre  produces  a  state  of  average  continued  activity,  which  is  respon- 
sible for  the  maintenance  of  arterial  tone  and  for  the  regulation  of  the 
arterial  blood  pressure. 

The  centre  may  also  be  affected  directly  by  changes  in  its  blood- 
supply,  or  in  the  composition  of  the  blood  flowing  through  it.  Thus 
anything  which  interferes  with  the  oxygenation  of  the  centre,  whether 
obstruction  to  respiration,  absence  of  oxygen  in  the  air  breathed,  or  a 
failure  of  the  blood-supply,  as  by  ligature  of  the  cerebral  arteries,  calls 
forth  an  increased  state  of  activity  of  the  centre.  This  can  be  best 
studied  by  observing  the  changes  in  the  blood  pressure  produced  in  a 
curarised  animal  by  the  cessation  of  artificial  respiration. 

The  changes  occurring  in  the  blood  pressure  in  asphyxia  depend 
partly  on  the  stimulation  of  the  vaso-motor  and  vagus  centres  by  the 
venous_bkiod,  and  partly  on  the  affection  of  the^art  itself.  These 
phenomena  are  best  observed  in  a  curarised  animal,  and  we  \\'ill  first 
consider  them  with  both  vagi  cut,  in  order  to  shut  out  the  action  of 
the  vagus  centre.  The  blood  pressure  is  registered  by  means  of  a 
mercurial  manometer  in  connection  ^\^th  the  carotid  artery.  On 
leaving  off  the  artificial  respiration,  the  blood  pressure  remains  at  the 
same  height  for  twenty  or  thirty  seconds,  the  only  change  noticed 
being  the  absence  of  the  respiratory  oscillations.  At  this  point  the 
blood  pressure  suddenly  rises  rapidly  (Fig.  457,  a),  and  in  another  ten 
seconds  may  reach  a  height  twice  as  great  as  it  was  previously.  The 
heart  beats  a  little  more  forcibly  in  consequence  of  the  increased  cardiac 
tension,  but  its  frequency  is  almost  unaltered.  The  blood  pressure 
remains  at  this  height  for  about  a  minute,  and  then  gradually  falls,  the 
heart-beats  becoming  smaller  and  smaller,  until  the  pressure  has  sunk  to 
a  point  very  little  above  the  abscissa  line  (level  of  no  pressure).  This  fall 
in  iwessure  is  dite  to  the  failure  of  the  heart.  The  heart,  badly  supplied 
with  oxygen,  cannot  overcome  the  high  resistance  presented  by  the 
contracted  arterioles ;  it  gets  overfilled,  and  gradually  loses  the 
l)ower  of  expelling  any  of  its>contents.  If,  when  the  blood  pressure 
has  sunk  to  its  lowest  poiiikt^e  heart  be  rapidly  cut  out  of  the  body, 
it  will  begin  to  beat  fair^j^forcibly,  being  relieved  of  the  excessive 
internal  tension.  The  vessels,  hovvj'pver,  remain  constricted  until  the 
death  of  the  animal.  This  is  ^J^ii^n  by  two  facts.  If,  while  the 
pressure  is  sinking,  artificial  reJi^ation  be  recommenced,  the  heart 
supplied  with  oxygen  at  once  begins  to  beat  more  forcibly,  and  the 
blood  pressure  mav  rise  to  an  even  gireater  height  than  immediately 

70 


1106  PHYSIOLOGY 

after  the  commencement  of  the  asphyxia.  Again,  if  the  volume  of 
the  kidney  be  recorded  by  means  of  the  oncometer,  the  rise  of  general 
blood  pressure  produced  by  asphyxia  is  seen  to  be  accompanied  by  a 
marked  shrinking  of  the  kidney,  and  this  shrinking  endures  until  the 
animal  dies,  showing  that  the  fall  of  blood  pressure  following  the 
rise  is  due,  not  to  a  giving  way  of  the  arterial  resistance,  but  to  failure 
of  the  heart. 

Similar  results  are  obtained  when  the  vessels  to  the  brain  are 
ligatured,  or  when  the  animal  has  to  respire  an  indifferent  gas  free 


200     f\ 

/           -150  on 

1/ 

>  >. 

Resp.off    -100 

1  1 

MM       M    M   1 

' 1 

A    '220 

r\ 

roff\ 

J 

/                -ISO 

liN 

on 

-100 

1    1 

Nitrogen 

1    I    M    1    M    1 

Fig.  457.      Blood  pressure  changes  in  a  cut.      A.  after  cessation  of  respiratory 
movements.    B,  as  a  result  of  artiBci  il  respiration  with  nitrogen.    (Mathis  jn.) 

from  oxygen,  such  as  nitrogen  (Fig.  457,  b)  or  hydrogen.  In  the  uncu- 
rarised  animal  the  rise  of  blood  pressure  is  associated  with  increased 
respiratory  movements  and  finally  with  convulsive  spasms  which  may 
involve  practically  every  muscle  of  the  body. 

We  have  spoken  above  of  the  phenomena  of  asphyxia  as  being 
due  to  the  circulation  of  venous  blood.  There  are,  however,  two 
factors  which  may  be  concerned  and  which  may  influence  the  medullary 
centres  and  the  heart.  When  the  renewal  of  the  lung  ventilation  is 
stopped  by  ligature  of  the  trachea  or  by  cessation  of  the  respiratory 
movements,  the  increasing  venosity  of  the  blood  involves  a  diminished 
percentage  of  oxygen  and  an  increased  percentage  of  carbon  dioxide, 
and  when  asphyxia  is  excited  by  cessation  of  the  circulation  through 
the  medullary  centres,  these  centres  may  suffer  at  the  same  time  from 
lack  of  oxygen  and  from  the  accumulation  of  carbon  dioxide.  The 
question  arises  whether  one  or  both  of  these  factors  are  concerned.    It 


NERVOUS  CONTROL  OF  THE  BLOOD-VESSELS      1107 

is  easy  to  investigate  the  action  of  each  separately.  A  pure  oxygen 
lack  may  be  brought  about  by  allowing  an  animal  to  breathe  some 
inert  gas,  such  as  nitrogen  or  hydrogen,  or  in  the  curarised  animal  one 
of  these  gases  may  be  administered  by  the  pump  used  for  artificial 
respiration.  The  effects  of  accumulation  of  carbon  dioxide  in  the 
blood  and  tissues  may  be  produced  by  the  administration  of  gaseous 
mixtures  containing  excess  of  oxygen,  i.e.  30  to  40  per  cent.,  with 
varying  percentages  of  carbon  dioxide.  In  the  first  case,  the  tension 
of  the  carbon  dioxide  in  the  blood  will  be  kept  below  normal ;  in  the 


220- 


ido- 


'^4 

\  100- 


off 


on 


CO 2  12-'^ per  cent 
0^  30  per  cent 


Jj^iu.  '^a^.     Asphysical  blood  pressure  changes  iu  curarised  cut.    A,  inhalation  of 
CO.,.     B,  injection  of  lactic  acid.      (Mathison.) 

second  case,  the  tension  of  oxygen  in  the  blood  will  be  kept  above 
normal.  In  order  to  obtain  results  uncomplicated  by  the  influence  of 
anaesthetics,  the  experiments  may  be  carried  out  in  animals  which 
have  been  deprived  of  consciousness  by  destruction  of  the  brain  above 
the  superior  corpora  quadrigemina.  At  different  times  physiologists 
have  been  inclined  to  ascribe  the  excitatory  phenomenon  of  asphyxia 
either  to  absence  of  oxygen  or  to  excess  of  carbon  dioxide.  Mathison 
has  shown  that  both  conditions  may  concur  in  the  production  of  the 
rise  of  blood  pressure  in  asphyxia.  In  Figs.  457  and  458  the  rise  of 
arterial  pressure  produced  by  a  short  period  of  asphyxia  is  compared 
with  that  produced  by  oxygen  lack,  by  a  surplus  of  carbon  dioxide,  and 
by  the  injection  of  lactic  acid  into  the  circulation.  There  are  certain 
minor  details  in  these  curves  which  are  of  interest.  When  the  oxygen  of 
the  lungs  is  rapidly  washed  out  with  a  neutral  gas  the  asphyxial  rise 
comes  on  about  half  a  minute  later  than  it  would  with  pure  asphyxia. 


1108 


PHYSIOLOGY 


Int.  Vol. 


B.P. 


In  the  latter  case  it  seems  that  the  first  rise  is  due  to  the  accumulation 
of  carbon  dioxide.  The  rise,  however,  under  nitrogen  when  it  occurs  is 
extremely  abrupt,  and  the  subsequent  fall  of  blood  pressure,  i.e.  the 
heart  failure,  is  earlier  in  onset  and  more  rapid  than  with  ordi- 
nary asphyxia.  When  excess  of  carbon  dioxide  is  administered,  i.e. 
5  to  10  per  cent.,  a  marked  rise  of  pressure  occurs  which,  like  that 

produced  by  oxygen  lack,  is 
almost  entirely  conditioned 
by  stimulation  of  the  vaso- 
motor centres  and  resulting 
constriction  of  the  peripheral 
arterioles.  If  a  loop  of  in- 
testine be  placed  in  a  ple- 
thysmograph,  it  will  be  seen 
that  the  rise  of  pressure  co- 
incides with  a  shrinkage  in 
volume  of  the  intestine, 
pointing  to  a  vascular  con- 
striction (Fig.  459).  The 
heart's  action,  as  we  have 
seen,  is  improved  rather 
than  otherwise  by  moderate 
increase  in  the  tension  of  car- 
bon dioxide  in  the  blood  cir- 
culating through  it.  Hence 
the  rise  of  blood-pressure  due 
to  the  vascular  constriction 
,,,.,.,„.        ,     .    ■  111     1  1  may  be  maintained  for  a  con- 

I'lG.  4o!>.  iraeiiig  ot  arterial  blood  pressure   and      .     •'  .     ■ 

of   intestinal  vohmie,   to   show  the    infliionee    siderable  period,    e.(j.  ten   to 

""IX  '^^'^T^'',A^''''''''Z^'^  ^^^  ^^''    *"'''""  fifteen  minutes,  and  we  do 
of  the  blood.     (Matiiison.)  .' 

not  get  the  rapid  fall  of  pres- 
sure due  to  failure  of  the  heart  that  is  observed  in  an  ordinary 
asphyxia  tracing.  If  partial  oxygen  lack  or  abnormally  increased 
tension  of  carbon  dioxide  be  continued  for  some  time,  a  state  of 
narcosis  or  paralysis  finally  ensues  which  affects  not  only  the  higher 
centres  but  also  those  of  the  medulla,  so  that  death  may  ensue  without 
convulsions  or  excessive  rise  of  blood  pressure. 

Is  there  any  common  factor  in  the  two  conditions  of  oxygen  lack  and 
carbon  dioxide  excess  which  may  account  for  the  similarity  in  their 
effects  ?  It  has  been  shown  that  whenever  there  is  a  deficiency  of 
oxygen  the  metabohsm  of  the  tissues  undergoes  alteration,  so  that  as 
a  result  of  activity,  e.g.  in  muscles,  lactic  acid  is  formed  instead  of 
carbon  dioxide.  Lactic  acid  can  therfeore  be  detected  in  the  blood 
whenever  violent  exercise  is  taken  sufficient  to  produce  dyspnoea,  or 


NERVOUS  CONTROL  OF  THE  BLOOD-VESSKLS      1109 

wJioii  the  access  of  ()XV';j;cii  is  diiiiiiiished  by  poisoning  with  carbon 
monoxide,  or  by  reducin^^  the  tension  of  this  gas  in  the  air  breathed. 
Oxygen  lack  can  be  regarded  therefore  as  synonymous  with  the  pro- 
duction of  lactic  acid.  Lactic  acid  introduced  into  the  blood-stream, 
as  is  shown  in  the  curve  in  Fig.  458,  b,  is  equally  efficacious  with 
oxygen  lack  or  with  carbon  dioxide  excess  in  the  production  of  a  rise 
of  blood  pressure  indistinguishable  from  the  asphyxial  rise.  It  seems 
therefore  that  the  common  factor  in  asphyxia  is  the  increased  acidity 
or  H'  ion  concentration  of  the  blood.  We  shall  have  occasion  to 
return  to  this  question  in  dealing  with  the  origin  of  the  respiratory 
movements. 

If  in  the  dog,  and  to  a  less  extent  in  other  animals,  the  vagi  be 
left  intact,  the  blood-pressure  tracing  during  asphyxia  has  quite 
another  appearance.  At  the  point  of  the  tracing  corresponding  to  the 
rapid  rise  in  the  previous  experiment  there  is  in  this  case  only  a  slight 
rise  of  pressure,  but  the  heart  begins  to  beat  very  slowly.  At  each 
beat  it  necessarily  sends  out  a  greater  volume  of  blood  than  when  it 
is  beating  more  frequently,  and  hence  the  oscillations  on  the  blood- 
pressure  curve  caused  by  the  heart-beats  become  very  large.  This 
slow  beat  is  due  to  the  action  of  the  vagus  centre,  and  is  at  once 
abolished  by  section  of  the  two  vagi.  The  sparing  of  the  heart  by 
means  of  this  vagus  action  enables  it  to  last  longer,  and  the  final  fatal 
fall  of  blood  pressure  due  to  heart  failure  comes  on  rather  later  than 
when  the  vagi  are  divided.  In  the  increased  vagus  action  which  occurs 
during  asphyxia  two  factors  are  probably  involved.  The  cardio-inhibi- 
tory  centre  in  the  medulla  probably  partakes  of  the  general  excitation 
of  the  medullary  centres  due  in  the  first  place  to  carbon  dioxide  excess, 
in  the  second  to  oxygen  lack.  More  important  is  the  direct  action  of  the 
rise  of  blood- pressure  on  the  medullary  centre.  The  rise  of  arterial 
pressure  causes  increased  intracranial  tension,  and  any  increase  of  the 
latter  excites  the  vagus  centre  and  produces  slowing  of  the  pulse.  The 
vagus  slowing  is  therefore  absent  in  asphyxia  if  the  arterial  blood  be 
allowed  to  escape  through  a  mercury  valve  so  as  to  prevent  any  rise 
of  pressure  in  the  brain  cavity. 

During  the  period  of  increased  pressure  waves  are  often  observed 
on  the  blood-pressure  curve.  These  are  of  two  kinds.  In  the  first 
place,  in  completely  ciu-arised  animals  we  may  observe  oscillations  of 
blood  pressure  corresponding  with  the  respiratory  rhythm  before 
the  administration  of  curare,  or  if  the  vagi  are  cut,  presenting  a 
rhythm  similar  to  that  usual  in  animals  with  divided  vagi.  These 
waves  are  known  as  the  Traube-Hering  curves  from  the  physiologists 
by  whom  they  wimc  first  observed.  They  are  certainly  due  to  irradia- 
tion of  impulses  from  the  excited  respiratory  centre  to  the  vaso-motor 
centre  in  the  medulla.     In  fact,  if  the  curarisation  is  not  complete,  a 


1110 


PHYSIOLOGY 


slight  twitch  of  the  diaphragm,  insufficient  by  itself  to  have  any- 
mechanical  influence  on  the  circulation,  may  be  observed  to  accompany 
each  rise  on  the  blood-pressure  curve.  Besides  the  Traube-Hering 
curves  others  are  occasionally  seen  which  must  arise  in  a  slow  rhythmic 
variation  of  the  constrictor  impulses  sent  out  from  the  vaso-motor 
centre.  These  waves  are  known  as  the  Mayer  curves,  and  are  not  to  be 
confused  with  the  waves  on  an  ordinary  pressure  burve  due  to  respira- 
tion, being  much  slower  in  their  rhythm  than  the  latter.  They  are 
observed  not  only  during  asphyxia,  but  may  occur  in  blood- pressure 


Fig.  460.     Blood -pressure  tracings  showing  S.  Mayer  curves.     (C.  J.  Martin.) 

tracings  from  normal  dogs,  and  are  frequent  in  dogs  poisoned  with 
morphia.  Fig.  460  represents  tracings  obtained  from  a  dog  under  the 
influence  of  morphia  and  curare.  The  upper  curve,  taken  while 
artificial  respiration  was  being  carried  on,  shows  the  three  forms  of 
curves — the  oscillations  due  to  the  heart-beat,  next  in  size  those 
due  to  the  respiratory  movements,  which  in  their  turn  are  super- 
posed on  the  slow  prolonged  curves,  i.e.  the  Mayer  curves.  The  lower 
curve  is  taken  immediately  after  cessation  of  the  artificial  respira- 
tion, and  shows  only  the  heart-beats  and  the  Mayer  curves.  The 
presence  of  Mayer  curves  may  generally  be  ascribed  to  a  state  of 
abnormal  excitation  of  the  vaso-motor  centre.  This  excitation  may 
arise  in  various  ways.  A  very  frequent  cause  is  the  one  just  described, 
viz.  increased  venosity  of  the  blood  supplied  to  the  centre.  Well- 
marked  Mayer  curves  are  often  observed  in  cases'  of  haemorrhage. 
In  spite  of  the  loss  of  blood,  the  vaso-motor  centres  maintain  a  normal 
arterial  blood  pressure  by  means  of  vascular  constriction.  As  the 
bleeding  continues,  this  means  becomes  inadequate,  and  at  this  point 


NERVOUS  CONTROL  OF  THE  BLOOD-VESSELS      11 11 

the  *  efforts  '  of  the  centres  take  on  a  rhythmic  character,  giving  well  • 
marked  Mayer  curves,  just  as  the  arm  of  a  man  holding  up  a  weight 
begins  to  shake  before  he  is  obliged  to  give  way  through  fatigue.  If 
the  bleeding  still  continues,  the  pressure  sinks  steadily  and  the 
curves  disappear.  The  curves  may  also  be  often  observed  during 
operations  involving  exposure  of  the  cord,  and  may  possibly  be 
ascribed  in  this  case  to  abnormal  irritations  ascending  the  posterior 
columns. 

The  vaso-motor  centre  may  also  be  directly  affected  by  drugs  such 
as  digitalis  or  strophanthus,  both  of  which  cause  a  rise  in  general  blood 
pressure  from  stimulation  of  the  centre. 

SPINAL  CENTRES 

The  great  fall  of  blood  pressure  observed  after  section  of  the 
cord  in  the  lower  cervical  region  is  not  permanent.  After  one  or 
two  hours  the  pressure  begins  to  rise,  and,  if  the  animal  be  kept 
alive,  may  attain  a  height  only  a  little  inferior  to  that  found  in  normal 
animals. 

If  the  spinal  cord  of  such  an  animal  be  destroyed,  the  blood 
pressure  sinks  practically  to  zero  and  the  circulation  comes  to  an  end, 
because  the  animal  has  been,  so  to  speak,  bled  to  death  into  its  own 
dilated  blood-vessels.  In  addition  to  the  chief  vaso-motor  centre 
in  the  medulla  there  is  a  series  of  subsidiary  centres  in  the  spinal 
cord,  centres  which  we  may  probably  locate  in  the  portions  of  grey 
matter  situated  in  the  lateral  horns  of  the  cord  and  giving  origin 
to  the  fibres  which  go  to  make  up  the  white  rami  com.municantes. 
By  means  of  these  spinal  centres  a  certain  degree  of  adaptation  is 
possible  between  the  blood-supply  of  the  various  parts  of  the  trunk. 
The  important  co-ordination  between  the  state  of  the  blood-vessels 
and  the  condition  of  the  central  pump,  the  heart,  is,  however,  wanting, 
since  the  blood-vessels  are  now  cut  off  from  the  cardiac  centres  and 
from  the  part  of  the  central  nervous  system  which  receives  the  afferent 
impulses  carried  by  the  vagi. 

The  spinal  centres,  like  the  chief  vaso-motor  centre,  are  susceptible 
to  changes  in  the  composition  of  the  blood  supplied  to  them.  If  an 
animal  be  kept  alive  by  means  of  artificial  respiration  for  a  little  time 
after  division  of  the  cord  just  below  the  medulla,  the  blood  pressure 
slowly  rises  as  the  spinal  centres  begin  to  take  on  their  automatic 
functions.  If  artificial  respiration  be  now  discontinued  the  asphyxia 
excites  the  centres  of  the  cord.  The  motor  discharge  to  the  skeletal 
muscles  reveals  itself  in  a  single  prolonged  spasm,  since  the  respiratory 
cenlivi  is  unable  to  take  any  part  in  directing  the  motor  discharges. 
Simultaneously   with   the   spasm   of    the   skeletal   muscles  [  general 


1112 


PHYSIOLOGY 


constrictions  of  the  blood-vessels  occur  which  outlast  the  muscular 
spasms  and  cause  a  considerable  rise  of  blood  pressure  (Fig.  461). 

In  this  rise  of  pressure  the  main  factor  is  lack  of  oxygen,  and 
precisely  similar  curves  are  obtained  whether  the  asphyxia  be  pro- 
duced by  cessation  of  artificial  respiration  or  by  administration  of 
nitrogen.  The  same  effect  may  be  produced  by  a  very  large  excess 
of  carbon  dioxide,  or  by  the  injection  of  acids  into  the  circulation. 
There  is  a  striking  difference  between  the  sensibility  of  the  spinal 
centres  to  these  substances  as  compared  with  the  medullary  centres. 


Fig.  461.  Blood-pressure  tracing  taken  by  a  mercurial  manometer  from 
carotid  artery  of  a  dog,  three  hours  after  section  of  the  cord,  just 
below  the  medulla  oblongata.  At  o  the  artificial  respiration  was  dis- 
continued .  A  general  spasm  of  the  skeletal  muscles  occurred  between 
X  and  X.  The  muscles  then  relaxed,  and  were  flaccid  during  the  rest  of 
the  rise  of  blood  pressure. 

Thus  the  medullary  vaso-motor  centre  is  readily  excited  by  5  per  cent, 
carbon  dioxide,  whereas  a  rise  of  blood  pressure  is  only  obtained  from 
the  spinal  animal  when  mixtures  containing  25  per  cent,  and  upwards 
of  carbon  dioxide  are  employed.  The  excitation  of  the  medullary 
centre  comes  on  about  thirty  seconds  after  the  administration  of 
nitrogen  has  commenced  in  contrast  to  that  of  the  spinal  centres, 
which  does  not  occur  until  two  minutes  or  more  have  elapsed.  In  the 
intact  animal  a  maximal  stimulation  of  the  vaso-motor  centre  is  pro- 
duced by  the  injection  of  2  c.c.  N/20  lactic  acid,  whereas  5c.c.  of  N/2 
acid  are  required  to  excite  spinal  cord  centres.  Here  therefore,  as  in 
the  medulla,  the  common  factor  is  probably  increased  H'  ion  concentra- 
tion, the  excitation  threshold  for  the  medullary  centres  being  only 
about  one-fifth  that  of  the  spinal  centres. 

The  local  spinal  centres  are  connected  with  the  medullary  vaso- 
motor centre  on  each  side  by  tracts  of  nerve  fibres  which  descend  in 
the  lateral  columns  of  the  cord. 


NERVOUS  CON'TROL  OF  THE  BLOOD-VESSELS      111.) 

THE  PERIPHERAL  TONE   AND   ADAPTATION  OF  THE 
BLOOD-VESSELS 

Division  of  the  sciatic  nerve  causes  an  immediate  dilatation  of  the 
vessels  of  tlie  lower  limbs  in  consequence  of  their  severance  from  the 
tonic  activity  of  the  vaso-motor  centres.  This  dilatation  passes  off 
i:i  a  day  or  two  and  the  vessels  acquire  a  tone,  i.e.  remain  in  a  state  of 
average  constriction  wliich  can  be  increased  or  diminished  by  local 
conditions.    This  recovery  of  tone  has  been  ascribed  by  many  physic- 


Spl.  exc. 

Time 
10  sec. 


Fig.  462.    EfEcct  of  excitation  of  splanchnic  nerves  on  the  blood  pressure  and 
on  the  volume  of  the  denervatcd  hind  limb  of  the  cat.     (Bayliss.) 


logists  to  the  existence  of  a  third  set  of  nerve-centres  in  the  walls  of  the 
arteries.  In  the  absence  of  any  direct  histological  evidence  of  the  exist- 
ence of  such  centres  it  seems  more  rational  to  ascribe  the  tonus  to  the 
automatic  activity  of  the  muscular  fibres  themselves.  Like  all  muscu- 
lar tissues,  the  arterial  wall  after  severance  from  all  its  nervous  connec- 
tions is  largely  influenced  by  tension,  increased  tension  acting  as  a 
stimulus  to  increased  contraction.  This  effect  may  be  observed  in 
the  isolated  arteries.  A  strip  of  the  carotid,  even  a  day  or  two  after 
death,  if  warmed,  may  respond  to  a  sudden  distending  force  by  a  slow 
contraction.  The  same  response  may  be  observed  in  denervated 
blood-vessels  through  which  the  circulation  is  well  maintained.  Thus, 
as  Bayliss  has  shown,  if  the  hind  limb,  after  division  of  all  its  nerves, 
be  placed  in  a  plothysmograph,  a  sudden  rise  of  general  blood  pressure, 
such  as  that  produced  by  stimulation  of  the  splanchnic  nerves,  may 
cause  an  immediate  passive  dilatation,  which  is  rapidly  followed  by  an 


1114  PHYSIOLOGY 

active  constriction  of  the  blood-vessels  of  the  limb  (Fig.  462).  On  the 
other  hand,  a  fall  of  blood  pressure  causes  relaxation  of  the  arterial 
wall,  so  that  the  primary  passive  fall  of  the  plethysmograph  lever  is 
succeeded,  even  during  the  maintenance  of  the  low  general  blocd 
pressure,  by  a  rise  to  its  normal  level  (Fig.  463).  Thus  increased  blood 
pressure  causes  contraction,  while  diminished  blood  pressure  causes 
relaxation  of  the  wall  of  the  arterioles — a  state  of  things  eminently 
adapted  to  the  maintenance  of  a  continuous  flow  of  blood  through  a 


Hind  limb 


Signal 

Time  10  sec. 

Fig.  463.  Effect  of  temporary  compression  of  the  abdominal  aorta  on  tlie 
volume  of  the  denervated  hind  limb.  Two  compressions,  the  second  not 
marked  by  the  signal.  Blood  pressure  taken  in  the  femoral  artery  of  one 
hind  limb,  the  other  hind  limb  being  in  the  plethysmograph.    (BayliSS.  ) 

part,  and  to  minimising  the  local  effects  of  the  alterations  of  general 
blood,  pressure  which  may  be  conditioned  by  changes  occurring  in  other 
parts  of  the  body. 

THE  COURSE   AND   DISTRIBUTION  OF  THE 
VASO-MOTOR  NERVES 

Since  the  blood-vessels,  like  the  heart,  are  the  seat  of  an  automatic 
activity,  complete  nervous  control  of  these  tubes  can  only  be  secured 
by  the  provision  of  two  sets  of  nerves  :  one  set — augmentor  or  motor 


NERVOUS  CONTROL  OF  THE  BLOOD-VESSELS      1115 

— which  will  increase  the  state  of  constriction  of  the  vessels  ;  another 
set — inhibitor  or  dilator — which  will  diminish  the  tone  of  the  arteriole 
muscle  and  cause  vascular  dilatation.  Our  knowledge  of  the  existence 
of  this  second  class  of  nerve  fibres  to  the  vessels  we  owe  also  to  Claude 
Bernard,  who  observed  that  stimulation  of  the  chorda  tympani  nerve 
not  only  evoked  secretion  from  the  submaxillary  gland  but  also  in- 
creased the  blood-flow  through  its  vessels  five-  or  sixfold.  Subsequent 
researches  have  revealed  the  fact  that  nearly  all  the  vessels  of  the  body 
receive  vaso-constrictor  fibres,  and  that  many  receive  also  vaso-dilator 
fibres.    In  order  to  determine  the  course  and  distribution  of  the  vascular 


Fig.  464. 


nerves  it  is  necessary  to  have  means  at  our  disposal  for  investigating 
the  condition  of  the  blood-flow  through  difierent  parts  and  organs  of 
the  body.  Let  us  see  what  effects  will  ensue  on  the  local  circulation 
by  constriction  or  dilatation  of  the  arterioles  with  which  it  is  supplied. 
If  the  arterioles  a  in  the  organ  b  dilate  (Fig.  -iGi),  the  first  effect  is  a 
diminution  of  the  resistance  to  the  flow  of  blood  into  the  capillaries 
beyond.  Supposing  that  the  arterial  pressure  in  the  trunk  c  remain 
constant,  a  local  diminution  of  resistance  in  a  will  at  once  determine  an 
increased  flow  of  blood  through  the  arterioles,  and  the  fall  of  pressure 
from  A  to  the  capillaries  ^vill  be  less  than  when  the  arteriole  was  con- 
stricted. If  the  organ  is  distensible  and  elastic,  the  increased  pressure 
in  the  arterioles  and  capillaries  will  cause  dilatation  of  these  vessels, 
and  a  consequent  dilatation  of  the  whole  organ.  The  same  effect  on 
intracapillary  pressure,  and  therefore  on  the  volume  of  the  part,  may 
be  caused  by  obstruction  to  the  flow  of  blood  from  the  veins.  Provided 
that  there  is  no  obstruction  to  the  flow  ofhhod  throvgh  the  vein,  and  that 
the  general  blood  pressure  in  c  remains  constant,  dilatation  of  an  organ 
may  be  taken  as  an  expression  of  vaso-dilatation  in  the  arteries  with 
which  it  is  supplied.    The  diminution  of  the  resistance  in  a  may  also 


1116 


PHYSIOLOGY 


increase  the  velocity  of  the  flow  through  the  part,  since  the  amount  of 
blood  flowing  in  a  given  period  of  time  through  any  vessel  varies 
directly  as  the  difference  of  pressure,  and  inversely  as  the  resistance 
in  the  vessel. 

We  can  therefore  use  the  following  criteria  for  the  occurrence  of 
a  vaso-dilatation  in  the  arterial  supply  to  any  part  or  organ : 

(1)  If  the  surface  of  the  part  is  translucent,  the  increased  filUng 
of  the  blood-vessels  will  cause  redness  or  blushing. 

(2)  The  increased  size  of  the  vessels  will  cause  an  increase  in  the 
volume  of  the  organ  concerned. 

(3)  An  increased  velocity  of  blood-flow  will,  if  the  part  be  normally 


>y'. 

I 


wmrnmim. 


IT 


to  oncometer 


Fic;.  465.     UiaKi'aiu  of  oncometer. 


Fig.  46(3.     Diagram  of  oncograph. 


below  the  temperature  obtaining  in  the  central  organs  of  the  body, 
raise  its  temperature,  and  vaso-dilatation  can  thus  be  detected  by 
the  application  of  the  hand  or  of  a  thermometer. 

(4)  Any  of  the  methods  mentioned  in  a  previous  chapter  may  be 
used  to  determine  the  velocity  in  the  arteries  going  to  the  part,  and  an 
increased  velocity  may  be  interpreted  as  due  to  vaso-dilatation. 

(5)  The  increased  flow  through  the  part  may  be  detected  by  cutting 
the  main  efferent  vein  and  measuring  the  total  volume  of  blood  which 
flows  from  it  in  a  given  time. 

Of  these  methods  the  two  most  used  are  those  based  on  determina- 
tion either  of  the  volume  of  the  part,  or  of  the  venous  outflow  from  the 
part.  A  fallacy  may,  however,  arise,  unless  means  be  taken  to  ensure 
that  the  general  arterial  pressure  remain  constant  during  the  experi- 
ment. A  rise  of  general  blood  pressure  wall  cause  an  expansion  of  the 
vessels  and  of  the  part  supplied,  and  also  increased  velocity  of  blood- 
flow  through  the  part.  In  all  cases  therefore  where  it  is  desired  to 
investigate  the  conditions  of  the  local  circulation,  it  is  necessary  to 
combine  a  determination  of  the  general  blood  pressure  with  some  means 
of  estimating  changes  in  the  local  conditions.  We  may  take  as  an 
instance  an  experiment  on  the  blood-supply  to  the  kidney. 


XERV0U8  CONTROL  OF  THE  BLOOD-VESSELS      1117 

For  this  purpose  we  may  use  a  kidney  plethysmograph  or  onco- 
meter. The  structure  of  Roy's  oncometer  is  shown  in  Fh^.  405. 
The  oncometer  is  a  metal  capsule,  the  two  halves  of  which  are  hinged 
together  and  come  in  contact  at  the  whole  of  their  circumference 
except  at  A,  where  a  small  depression  is  left  in  each  half  for  the  passage 
of  the  kidney  vessels  and  ureter.  A  piece  of  peritoneal  membrane  is 
attached  to  the  rim  of  each  half  of  the  oncometer,  the  space  between 
this  and  the  brass  capsule  being  filled  with  warm  oil.  The  kidney 
rests  in  the  oncometer  on  this  bed  of  warm  oil,  from  which  it  is  separated 
by  a  membrane.     A  tube  leads  from  the  cavity  between  the  brass 


Fig.  467.     Diagram  of  Schiifei's  air  plethysmograph. 

capsule  and  membrane  to  a  registering  apparatus,  or  oncograph  (Fig. 
466),  which  is  a  piston  recorder  containing  oil.  Any  swelling  of  the 
kidney  will  drive  oil  out  of  the  oncometer  into  the  cylinder  of  the 
oncograph  and  so  raise  the  piston,  the  excursions  of  which  are  recorded 
by  a  lever  writing  on  a  blackened  surface. 

Schafer's  plethysmograph  (Fig.  467),  which  can  be  adapted  to 
almost  any  organ  of  the  body,  is  made  of  vulcanite  *  previously  moulded 
to  the  size  of  the  organ  whose  volume  is  the  object  of  investigation.  In 
one  side  of  the  box  a  depression  is  left  sufficient  to  accommodate 
easily  the  vessels,  nerves,  or  ureter  going  to  the  organ.  The  oncometer 
is  covered  with  a  glass  lid  which  is  made  air-tight  by  means  of  vaseline, 
the  space  between  the  lid  and  the  vessels  being  also  packed  with  cotton- 
wool and  vaseline.  A  glass  tube  is  fixed  into  one  corner  of  the  plethys- 
mograph and  leads  to  a  piston  recorder  or  tambour.  Every  variation 
in  the  volume  of  the  organ  causes  a  movement  of  air  into  or  out  of  the 
oncometer  and  thus  gives  rise  to  a  corresponding  movement  of  the 
recording  lever. 

*  A  very  good  material  for  tlxis  purpose  is  '  Stent's  eomposition,'  used  hy 
dentists  for  taking  a  mould  of  the  jaw  in  fitting  artificial  teeth. 


1118 


PHYSIOLOGY 


The  kidney  being  placed  in  some  such  apparatus,  a  cannula  is  also 
placed  in  the  carotid  artery  and  connected  with  a  mercurial  mano- 
meter, so  that  two  tracings  are  obtained  at  the  same  time  on  the 
moving  blackened  surface.  In  the  figure  given  (Fig.  468),  the  upper 
curve  represents  the  carotid  blood  pressure,  while  the  lower  is  the 
tracing  of  the  oncograph  lever.  At  the  beginning  of  the  experiment 
the  lower  dorsal  nerve-roots  had  been  dissected  out  and  prepared  for 
stimulation  at  the  point  marked  with  a  cross  on  the  tracing.  The  peri- 
pheral end  of  the  anterior  root  of  the  tenth  dorsal  nerve  was  excited  by 
means  of  an  interrupted  current.  This  stimulation  was  followed  by  a 
rise  of  blood  pressure  together  with  a  diminution  in  the  kidney  volume. 
The  increased  blood   pressure  would  by  itself  tend  to  force  more 


^■""^ 

.,.^~" 

^ 

■'""''^''"----v--^ 

3od  pressure 

' 

Kidney 

volume 

""^..y''^ 

\ 
\ 

/ 

V  '"* 

n^c\ 

./'....     1      ,     ...     1     ....     1     1    L^-^ 

i\ 

\    ^ 

...]... 

\        _-/ 

Fig.  4G8.     Simultaneous  tracings  of  carotid  blood  pressure  and  volume  of 
y  ^kidney.    Between  x  and  x  the  peripheral  end  of  the  divided  tenth  dot'sal 
nerve  was  stimulated.    Time-mar  king  =  seconds.     (Bradfokd.) 

blood  into  the  kidney  and  so  increase  its  volume.  The  fact  that  the 
kidney  volume  diminished  shows  that  there  must  have  been  active 
contraction  of  the  arterioles  of  the  kidney,  emptying  this  organ  of 
blood  and  so  causing  it  to  decrease  in  size.  This  contraction  of  the 
vessels  would  tend  to  cause  a  rise  in  general  blood  pressure  and  must 
have  taken  some  part  at  any  rate  in  the  rise  actually  observed.  If  the 
oncometer  in  this  experiment  had  been  used  alone,  it  would  have 
been  impossible  to  have  determined  whether  the  shrinkage  of  the 
kidney  might  not  have  been  due  to  a  lowering  of  general  blood 
pressure,  in  consequence  of  vaso-dilatation  occurring  elsewhere,  or  in 
consequence  of  the  failure  of  the  heart's  activity.  On  the  other  hand, 
without  the  oncometer  it  would  only  have  been  possible  to  determine 
that  there  was  increased  peripheral  resistance  somewhere  or  other  in 
the  body. 


NERVOUS  CONTROL  OF  THE  BLOOD-VESSELS      1119 

Instead  of  taking  the  volume  of  tlie  kidney  \\v  might  liavu  determined  llie 
blood-llow  tlirough  its  vessels  cither  directly  by  means  of  a  cannula  in  the  renal 
vein,  or  by  the  indirect  method  of  Brodie.  'J'his  method  depends  on  the  fact  that 
under  normal  conditions  the  amount  of  blood  leaving  an  organ  is  equal  to  that 
entering  it  during  any  short  space  of  time.  If  the  efferent  vein  be  clamped  fo 
five  or  ten  seconds,  the  blood  entering  the  organ  during  this  time  cannot  escape, 
and  therefore  accumulates  in  the  organ  and  increases  its  volume.  If  the  organ 
be  in  a  plethysmograph  the  increase  of  volume  during  tliis  period  may  be  measured 
and  is  exactly  equal  to  the  volume  of  blood  passing  through  the  artery  into  the 
organ  during  the  five  or  ten  seconds  of  the  closure.  The  vein  must  not  be 
ob.structed  too  long,  otherwise  the  increasing  distension  of  the  organ  Avill  appre- 
ciably increase  the  resistance  to  the  entry  of  blood,  and  so  diminish  the  velocity 
of  the  blood  in  the  artery. 

The  direct  determination  of  the  venous  outflow  is  not  well  adapted  to  large 
organs  on  account  of  the  very  rapid  loss  of  blood  wliich  occurs  through  the  open 
vein.  The  method  is,  however,  of  great  value  in  dealing  with  the  circulation 
through  small  organs  such  as  the  submaxillary  glands.  In  such  a  caae  it  is  usual 
to  hinder  or  prevent  the  clotting  of  the  blood  by  the  prehminary  injection  of 
leech  extract,  and  then,  after  placing  a  cannula  in  the  efferent  veins  of  the  organ, 
to  allow  blood  from  the  cannula  to  drop  on  to  a  mica  disc  attached  to  a  Marey 
tambour.  This  tambour  is  connected  by  a  tube  with  a  registering  tambour,  every 
drop  on  the  disc  giving  rise  to  a  small  elevation  of  the  lever  of  the  second  tambour. 


COURSE  OF  THE  VASO-CONSTRICTOR  FIBRES 

In  investigating  the  course  of  the  vaso-constrictor  fibres  we  have 
to  determine  : 

(1)  The  origin  of  the  fibres  from  the  central  nervous  system  ; 

(2)  The  course  of  the  fibres  on  their  way  to  their  peripheral  dis- 
tribution in  the  blood-vessels ; 

(3)  Their  connections  with  nerve-cells. 

The  two  first  details  can  be  found  by  stimulating  various  nerves 
and  nerve-roots  in  different  parts  of  their  course  and  observing  the 
effects  produced  on  the  local  and  general  circulation.  The  importance 
of  the  third  heading  is  due  to  the  fact  that  the  vascular  nerves,  like  the 
visceral  nerves  generally,  do  not  have  their  last  cell-station  in  the 
spinal  cord.  The  fibres  carrying  vaso-constri(?tor  impulses,  on  leaving 
the  cord,  do  not  pass  direct  to  the  blood-vessels,  but  come  to  an  end  in 
a  collection  of  ganglion-cells,  which  may  belong  to  the  main  chain  of 
the  sympathetic,  or  be  situated  more  distally  and  belong  to  the  group 
of  collateral  or  peripheral  ganglia.  These  fibres,  as  they  leave  the 
central  nervous  system,  are  small  medulhited  nerves.  They  end  in 
the  gangUon  by  arborising  round  ganglion-cells,  whence  a  fresh  relay 
of  fibres  starts  and  carries  the  impulses  on  to  the  muscle  fibres  of 
the  blood-vessels.  The  post-ganglionic  fibres  differ  from  the  pre- 
ganglionic fibres  in  being  non-medullated. 

The  discovery  of  the  ganglia,  with  which  any  given  set  of  nerve 
fibres  is  connected,  is  rendered  easy  by  the  fact  that  in  many  animals 


1120  PHYSIOLOGY 

the  sympathetic  ganglion -cells  are  paralysed  by  nicotine  (Langley). 
The  nicotine  may  be  painted  on  the  ganglion  or  may  be  injected  into 
the  blood-stream.  The  first  effect  of  the  drug  is  a  powerful  stimula- 
tion of  the  ganglion-cells,  so  that,  if  the  drug  be  injected,  there  is  an 
enormous  rise  of  blood  pressure  owing  to  the  universal  vaso-con- 
striction  that  is  produced.  The  stimulation  gives  place  to  a  condition 
of  paralysis ;  the  blood  pressure  falls  below  normal,  owing  to  the 
cutting  off  of  the  peripheral  vascular  nerves  from  the  vaso-motor  centre. 
Stimulation  of  the  pre-ganglionic  fibre  is  now  without  effect,  although 
the  normal  results  follow  stimulation  of  the  post-ganglionic  non- 
medullated  fibre. 

By  these  methods  it  has  been  determined  that  all  the  vaso-con- 
strictor  nerves  of  the  body  leave  the  spinal  cord  by  the  anterior  roots 
of  the  spinal  nerves  from  the  first  dorsal  to  the  third  or  fourth  lumbar 
inclusive.  From  the  roots  they  pass  by  the  white  rami  communicantes 
to  the  gangha  of  the  sympathetic  chain  lying  along  the  front  of  the 
vertebral  column.  Here  they  take  different  courses  according  to  their 
destination. 

The  fibres  to  the  head  and  neck  leave  by  the  first  four  thoracic  nerves, 
pass  into  the  sympathetic  chain  through  the  ganglion  stellatum  and 
ansa  Vieussenii  to  the  inferior  cervical  ganglion,  and  up  the  cervical 
sympathetic  trunk  to  the  superior  cervical  ganglion.  Here  they  end, 
and  the  impulses  are  carried  by  a  fresh  relay  of  fibres,  which  start  from 
cells  in  this  ganglion  and  travel  as  non-medullated  fibres  on  the  walls 
of  the  carotid  artery  and  its  branches. 

The  constrictors  to  the  fore  limb  in  the  dog  leave  the  cord  by  the 
white  rami  of  the  fourth  to  the  tenth  thoracic  nerves.  The  fibres  run 
up  the  sympathetic  chain  to  the  stellate  ganglion,  where  they  all  end 
in  synapses  round  the  cells  of  this  ganglion.  The  impulses  are  carried 
on  by  non-medullated  fibres  along  the  grey  rami  of  the  sympathetic 
to  the  cervical  nerves  which  make  up  the  brachial  plexus,  and  run 
down  in  the  branches  of  this  plexus  to  be  distributed  to  the  vessels 
of  tlie  fore  limb. 

The  constrictor  impulses  to  the  hind  limb  in  the  dog  arise  from 
the  nerve-roots  between  the  eleventh  dorsal  and  third  lumbar  roots. 
All  the  fibres  end  in  connection  with  cells  in  the  sixth  and  seventh 
lumbar  and  first  and  second  sacral  ganglia  of  the  sympathetic  chain, 
whence  the  impulses  are  carried  by  grey  rami  to  the  nerves  making 
up  the  sacral  plexus. 

The  most  important  vaso-motor  nerve  of  the  body  is  the  splanchnic 
nerve.  This  nerve  receives  most  of  the  fibres  forming  the  white  rami 
from  the  lower  seven  dorsal  and  upper  two  or  three  lumbar  roots,  the 
latter  fibres  often  taking  a  separate  course  as  the  lesser  splanchnics. 
The  fibres  can  be  seen  to  pass  through  the  sympathetic  chain  of  the 


NERVOUS  CONTROL  OF  THE  BLOOD-VESSELS      1121 

thorax  without  interruption,  and  for  the  most  part  have  their  cell- 
station  in  the  large  ganglia,  especially  the  semilunar  ganglia,  of  the 
solar  plexus,  whence  a  thick  meshwork  of  n<ni-niedullated  fibres  is 
distributed  along  all  the  vessels  of  the  abdominal  viscera.  The  area 
of  the  vessels  innervated  by  this  nerve  is  so  large  that  section  of  this 
nerve  on  each  side  causes  a  large  fall  in  the  general  blood  pressure. 
This  fall  is  more  marked  in  animals  such  as  the  rabbit  and  other  herbi- 
vora,  in  which  the  alimentary  canal  is  proportionately  very  much 
developed,  and  has  consequently  a  very  large  blood-supply. 


VASO-DILATOR  NERVES 

Since  the  arteries  are  in  a  constant  condition  of  moderate  con- 
traction, a  dilatation  might  be  brought  about  by  a  relaxation  of  this 
tone  by  an  inhibition  of  the  normal  constrictor  impulses  proceeding 
to  the  vessels  from  the  vaso-motor  centre.  We  find,  however,  in  many 
parts  of  the  body  evidence  of  the  existence  of  a  nerve-supply  to  blood- 
vessels antagonistic  in  its  function  to  the  vaso-constrictors.  Thus,  if 
the  chorda  tympani  nerve  going  to  the  submaxillary  gland  be  cut,  no 
change  is  evident  in  the  blood-vessels  of  the  gland.  But  if  its  peri- 
pheral end  be  stimulated  there  is  instantly  free  secretion  of  saliva 
from  the  gland,  and  all  the  blood-vessels  are  largely  dilated.  In 
consequence  of  this  dilatation  the  blood  rushes  through  the  capillaries 
so  quickly  that  it  has  no  time  to  lose  much  of  its  oxygen  ;  the  blood 
flowing  from  the  vein  is  therefore  bright  arterial  in  colour,  and  is 
increased  to  six  or  eight  times  the  pre\'ious  amount.  If  atropine  be 
injected  into  the  animal,  the  action  of  the  chorda  t}Tnpani  on  the 
blood-vessels  is  unaffected,  although  the  secretion  on  stimulation  is 
abolished.  The  chorda  tympani  is  therefore  said  to  contain  vaso- 
dilator fibres  for  the  vessels  of  the  submaxillary  gland.  Other  examples 
of  vaso-dilator  (or  dilatator)  nerves  are  the  small  petrosal  nerve  to  the 
parotid  gland,  the  lingual  nerve  to  the  blood-vessels  of  the  tongue,  and 
the  nervi  erigentes  or  pelvic  visceral  nerves  to  those  of  the  penis. 

The  course  of  these  typical  dilator  nerves  differs  widely  from  that 
of  the  constrictors.  Whereas  the  latter  leave  the  central  nervous 
system  over  a  limited  area  of  the  cord,  the  vaso-dilators  take  their  origin 
together  with  any  of  the  cerebro-spinal  nerves.  Thus  the  chorda 
tympani  fibres,  and  probably  those  contained  in  the  petrosal  nerve, 
arise  from  the  nervus  intermedins  between  the  seventh  and  eighth 
cranial  nerves.  The  nervi  erigentes  leave  the  lower  end  of  the  cord  by 
the  anterior  roots  of  the  second  and  third  sacral  nerves.  All  of  them, 
like  the  vaso-constrictors  and  probably  all  visceral  nerve  fibres,  are 
interrupted  by  ganglion-cells  before  reaching  to  their  destination. 
These  cells,  however,  lie,  not  in  the  lateral  chain  of  the  sjTiipathetic, 

71 


1122 


PHYSIOLOGY 


with  which,  the  nerves  have  no  connection  at  all,  but  peripherally,  and 
are  generally  embedded  in  the  organs  to  which  the  nerves  are  dis- 
tributed. Thus  the  chorda  tympani  fibres  to  the  submaxillary  glands 
are  interrupted  by  cells  embedded  in  the  gland  itself.  The  nervi 
erigentes  pass  to  ganglion-cells  in  the  hypogastric  plexus  lying  on  the 
neck  of  the  bladder. 

Whether  any  large  numbers  of  the  fibres  making  up  the  sympa- 
thetic system  of  nerves  are  vaso-dilator  in  function  is  still  uncertain. 
In  the  dog  dilatation  of  the  vessels  of  the  soft  palate  and  gums  can 
be  produced  by  stimulation  of  the  cervical  sympathetic  of  the  same 


~^ 

/ 

Nerve  freshly  divided. 
Constriction. 


Nerve  four  days  degenerated. 
Dilatation. 


Fig.  469.  Plethysmographic  tracing  of  hind  limbs,  showing  effect  of  stimu- 
lating the  sciatic  nerve  on  the  volume  of  the  limb,  A,  immediately  after 
section  of  the  nerve  ;  B,  four  days  after  section.  The.  nerve  was  stimu- 
lated between  the  two  vertical  lines.  Curves  to  be  read  from  right  to 
left.     (BowDiTCH  and  Wakken.) 

side,  or  of  the  stellate  ganglion  or  its  rami  communicantes.  The  effect 
has  not  yet  been  observed  in  any  other  animals.  It  is  probable  that 
the  splanchnic  nerves  convey  vaso-dilator  fibres  to  the  vessels  of  the 
abdomen,  since  stimulation  of  these  nerves  may  cause  a  fall  of  blood- 
pressure,  provided  that  the  constrictor  fibres,  which  predominate,  have 
been  paralysed  by  the  previous  administration  of  large  doses  of  the 
active  principle  of  ergot. 

The  presence  of  vaso-dilator  fibres  in  the  nerves  going  to  the  limbs 
has  been  the  subject  of  much  debate.  Since  these  nerves  contain 
also  constrictor  fibres,  the  effect  of  the  constriction  overpowers  any 
effects  due  to  simultaneous  stimulation  of  possible  dilator  fibres. 
Moreover  the  dilators  apparently  do  not  conduct  any  tonic  influences 
to  the  blood-vessels,  so  that  the  only  effect  of  section  of  a  mixed  nerve 
is  that  due  to  the  removal  of  the  tonic  constrictor  influences,  and  the 
vessels  in  the  area  of  distribution  of  the  nerves  are  dilated. 

Various  methods  have  been  employed  to  show  the  presence  of 
dilator  fibres  in  such  a  mixed  nerve-trunk.  Of  these  the  chief  two  are 
those  depending  on  the  unequal  time  taken  for  the  two  sets  of  fibres  to 
degenerate  and  on  the  varying  excitability  of  the  two  sets  of  fibres 
to  different  kinds  of  stimulation.  Thus,  if  the  sciatic  nerve  be  cut, 
a  primary  dilatation  of  the  vessels  of  the  leg  and  foot  is  produced, 


NERVOUS  CONTROL  OF  THE  BLOOD-VESSELS      1123 

which,  however,  passes  of!  after  two  or  three  days.  If  now  the  peri- 
pheral end  of  the  divided  nerve  is  stimulated,  dilatation  of  the  vessels 
is  produced  (Fig.  4(59).  Apparently  the  constrictor  fibres  degenerate 
before  the  dilator  fibres,  so  that  at  a  certain  period  after  the  nerve 
section  only  the  latter  respond  to  stimulation.  On  the  other  hand, 
it  is  often  possible  in  the  freshly  cut  nerve  to  obtain  dilatation  by 
stimulating  its  peripheral  end  with  induction  shocks  repeated  at  slow 


1   jjcr  sec. 


4  per  sec. 


6  per  sec. 
64  per  sec. 


Fig.  470.  Effect  on  the  volume  of  the  hind  limbs  of  the  cat  of  stimulating 
the  sciatic  nerve  with  induction  shocks  at  different  rates.  It  will  be 
noticed  that  \vith  one  shock  per  second  there  is  hardly  any  constriction, 
but  considerable  dilatation,  whereas  with  64  shocks  per  second  the 
only  effect  produced  Is  vaso-constrictiou.  Curves  to  be  rcixd  from  right 
to  left.     (BowDiTcn  and  AVarren.) 


intervals — one  to  four  per  second.     The  effects  of  different  rates  of 
stimulation  on  the  limb-nerves  of  the  cat  are  shown  in  Fig.  470. 

When  we  endeavour  to  trace  these  limb  dilator  fibres  back  to  the 
cord  we  find  no  trace  of  their  passage  through  the  sympathetic  system. 
It  was  shown  by  Strieker  and  Morat  that  dilatation  of  the  vessels 
of  the  hind  limb  can  be  produced  by  stimulating  the  posterior  roots 
of  the  nerves  going  to  the  limb,  i.e.  far  below  the  point  of  origin  of 
the  constrictor  fibres  to  the  same  part  of  the  body.  Since  it  has  been 
definitely  shown  by  embryologists  and  histologists  that  in  higher 
mammals  all  the  fibres  making  up   the  posterior  roots  have   their 


1124 


PHYSIOLOGY 


origin  in  the  cells  of  the  posterior  root-ganglion,  this  observation  was 
widely  discredited,  until  it  was  confirmed  by  Bayliss  for  all  manner 
of  stimuli.  Stimulation  of  the  posterior  roots,  either  before  or  after 
they  have  passed  through  the  ganglia,  causes  dilatation  of  the  vessels 
in  the  area  of  the  supply  of  the  roots,  whatever  be  the  nature  of  the 
stimulus  employed,  whether  electrical,  chemical,  or  mechanical  (Fig. 
471).  This  effect  is  not  destroyed  by  previous  section  of  the  posterior 
roots  on  the  proximal  side  of  the  ganglia,  showing  that  the  fibres 
by  means  of  which  the  dilatation  is  produced  have  the  same  origin 
and  course  as  the  ordinary  sensory  nerves  to  the  limbs.     Since   the 


^''((Ntm^^it^^ 


Fig.  471.     Effect  of  excitation  of  peripheral  end  of  seventh  lumbar  posterior 
^         root  in  the  dog.     (Bayliss.) 
Uppermost    curve,    volume  of  left  hind  limb  ;   next  below,   arterial 
blood  pressure  ;  the  third  line  marks  the  period  of  stimulation  ;   bottom 
line,  time-marking  in  seconds. 


vaso-dilator  impulses  pass  along  these  nerves  in  a  direction  opposite 
to  that  taken  by  the  normal  sensory  impulses,  Bayliss  has  designated 
them  as  antidromic  impulses.  So  far  this  phenomenon  of  a  nerve- 
fibre  functioning  (not  merely  conducting)  in  both  directions  is  almost 
without  analogy  in  our  knowledge  of  the  other  nerve-functions  of 
the  body.  There  is  no  doubt,  however,  that  similar  antidromic 
impulses  are  involved  in  the  production  of  the  so-called  trophic  changes, 
such  as  localised  erythema  or  the  formation  of  vesicles  (as  in  herpes 
zoster),  which  may  occur  in  the  course  of  distribution  of  a  sensory  nerve, 
and  is  always  found  to  be  associated  with  changes,  inflammatory  or 
otherwise,  in  the  corresponding  posterior  root  ganglia.  Moreover 
evidence  has  been  brought  forward  that  these  fibres  may  take  part 
in  ordinary  vascular  reflexes  of  the  body,  that  in  fact  they  are  normally 
traversed  by  impulses  in  either  direction. 

Some  observations  by  Hans  Meyer  and  Bruce  tend  to    indicate 


NERVOUS  CONTROL  OF  THE  BLOOD-VESSELS      1125 

that  in  the  antidromic  vaso-dilatation,  as  well  as  in  the  redden- 
ing and  inflammatory  changes  ensuing  on  local  excitation,  we  are 
dealing  with  axon  reflexes,  perhaps  the  only  remains  of  the  local 
reflexes  of  a  primitive  peripheral  subcutaneous  nervous  system. 
If  croton  oil  or  mustard  oil  be  applied  to  the  skin  or  to  the  conjunc- 
tiva, redness,  swelling,  and  all  the  signs  of  a  local  inflammation  are 
produced.  The  course  of  events  is  not  altered  by  destruction  of  the 
central  nervous  system  or  by  section  of  the  sensory  nerve-roots  (pos- 
terior spinal  root  or  trigeminus)  on  the  central  side  of  the  ganglion. 
If,  however,  they  be  divided  peripherally  of  the  ganglion,  and  time  be 


sup.  nerve  plex. 


1 


.n.f. 


FiQ.  472.     Diagram  to  illustrate  the  production  of  vaso-dilatation  in  the 

area  of  distribution  of  a  sensory  nerve. 

frg,  posterior  root  ganglion ;  sens.nf,  sensory  nerve  fibre,  branching  to 

supply  dilator  fibres  to  the  skin  arteries,  and  sensory  fibres  to  the  skin. 

allowed  for  complete  degeneration  of  the  nerve  fibres  to  their  peri- 
pheral terminations,  the  application  of  croton  or  mustard  oil,  even  to  the 
delicate  conjunctiva,  is  without  effect.  The  same  results  may  be  pro- 
duced if  the  peripheral  terminations  of  the  nerves  be  paralysed  by  the 
subcutaneous  injection  of  local  anaesthetics.  We  must  assume  that 
the  axons  of  the  peripheral  sensory  nerves  branch,  some  branches 
going  to  the  surface,  others  to  the  muscle-cells  of  the  cutaneous 
arterioles,  as  indicated  in  the  diagram  (Fig.  472). 

Gaskell  has  drawn  an  analogy  between  the  nerves  distributed  to  the 
blood-vessels  and  those  going  to  the  heart,  which  is  indeed  only  a 
specialised  part  of  the  general  blood-tubes  of  the  body.  These  nerves, 
according  to  their  action  on  the  metabolic  activity  of  the  tissues  supplied, 
are  divided  by  Gaskell  into  anabolic  and  catahoJic  nerves.  The  anabolic 
nerves,  as  indicated  by  their  name,  cause  a  building  up  or  regeneration 
of  the  contractile  tissue.     They  therefore  act  as  inhibitory  nerves. 


1126  PHYSIOLOGY 

This  class  would  include  the  vagus  and  the  vaso-dilator  fibres.  The 
catabolic  nerves  cause  an  increased  activity  of  the  contractile  tissue, 
and  active  contraction  is  associated  with  and  derives  its  energy 
from  disintegration  or  catabolism  of  the  muscular  substance.  An 
ordinary  motor  nerve  to  a  muscle  is  therefore  a  catabolic  nerve. 
This  class  would  include  the  accelerator  nerves  to  the  heart,  and  the 
vaso-constrictors.  The  course  of  these  two  sets  of  nerves  bears  out 
this  comparison,  the  path  taken  by  the  accelerator  nerves  being 
identical  at  first  with  that  of  the  vaso-constrictor  fibres  to  the  head  and 
neck. 

VASO-MOTOR  REFLEXES 

The  vaso-motor  centre  with  its  efferent  tracts  is  constantly  played 
upon  by  impulses  arriving  at  it  from  the  vascular  system,  including 


Fig.  473.  Blood-pressure  ctirve  from  carotid  of  dog.  Between  the  arrows 
the  central  end  of  a.  sensory  nerve  was  stimidated.  (Hurthle's 
manometer. ) 

both  heart  and  blood-vessels,  from  the  viscera,  from  the  muscles, 
and  from  the  surface  of  the  body.  The  reflex  effects  produced  by 
stimulation  of  the  various  afferent  nerves  may  be  classified,  according 
as  they  affect  the  general  blood  pressure  or  the  circulation  through 
restricted  areas  of  the  body,  as  general  and  local. 

The  afferent  impulses  affecting  the  general  blood  pressure  are  dis- 
tinguished as  pressor  and  depressor,  and  these  names  are  sometimes 
applied  to  the  nerves  which  carry  the  impulses.  A  pressor  reflex  is 
one  which  induces  a  rise  of  general  blood  pressure  by  constriction  of 
the  blood-vessels,  especially  in  the  splanchnic  area  (Fig.  473).  Effects 
of  this  kind  are  produced  by  stimulation  of  nearly  all  the  sensory  nerves 
of  the  skin.  Practically  all  impulses  which,  if  consciousness  were 
present,  would  be  attended  with  pain  cause  also  a  rise  of  general  blood 
pressure.  A  rise  of  pressure  may  be  produced  by  the  stimulation  of 
such  nerves  as  the  fifth,  the  central  end  of  the  splanchnic  nerves, 
or  of  the  nerves  distributed  to  the  surface  of  the  body.  This  rise 
occurs  in  all  animals  under  morphia  and  curare.     In  the  rabbit,  when 


NERVOUS  CONTROL  OF  THE  BLOOD-VESSELS      1127 

anaesthesia    is    induced  by   means  of  chloral  or  chloroform,  stimula- 
tion of  sensory  nerves  may  cause  a  fall  of  blood  pressure. 

The  chief  example  of  a  depressor  nerve  we  have  already  studied 
in  dealing  with  the  reflexes  from  the  heart.  ^  The  fall  of  pressure  pro- 
duced by  stimulation  of  this  nerve  is  effecte'd  chiefly  by  dilatation  of 
the  splanchnic  area  (Fig.  474),  though,  as  Bayliss  has  shown,  practically 
all  the  vessels  of  the  body  partake  in  the  relaxation.  The  lowering  of 
blood  pressure  produced  by  stimulation  of  this  nerve  differs  from  that 
obtained  on  stimulating  the  sensory  nerves  of  the  rabbit  under  chloral, 
in  that  its  effect  lasts  as  long  as  the  stimulation  is  continued,  whereas 


i;,p, 


Spleen 


Fig.  474.  Simultaneous  tracing  of  arterial  blood  pressure  and  splenic  volume 
from  a  rabbit,  showing  the  marked  swelling  of  the  spleen  associated 
with  fall  of  general  blood  pressure  on  stimulation  of  the  central  end 
of  the  depressor  nerve.  The|nerve  was  excited  between  a  and  h.  (  Bayliss. ) 


in  the  latter  case  the  effect  shows  signs  of  fatigue  and  disappears 
before  the  excitation  is  shut  off. 

So  far  as  the  general  blood  pressure  is  concerned  the  most 
important  impulses  arriving  at  the  centre  are  those  from  the  vascular 
system,  especially  from  the  heart  itself,  and  those  from  the  higher 
parts  of  the  brain.  Whatever  the  condition  of  the  heart  the  brain 
always  demands  a  normal  arterial  pressure,  since  on  this  depends 
the  supply  of  a  proper  quantum  of  blood  to  the  master  tissues  of  the 
body.  A  failing  heart  therefore  evokes  indirectly  constriction  of  the 
blood-vessels,  a  fact  which  may  lead  to  a  vicious  circle  in  cases  where 
the  heart  is  unable  to  perform  its  normal  functions  and  to  empty  itself 
against  the  resistance  of  the  blood-vessels.  In  this  case  the  heart 
dilates  more  and  more,  until  the  sUghtest  increase  in  the  demands 
upon  it,  as  by  a  slight  muscular  exertion,  may  suffice  to  stop  its  action 
altogether. 

Under  normal  circumstances  every  part  of  the  body  receives 
just  so  much  blood  as  it  needs  for  its  metabolic  requirements.    Hence 


1128 


PHYSIOLOGY 


activity  must  be  associated  with  an  increased  flow  of  blood  through 
the  part.  Two  mechanisms  are  involved  in  the  production  of  this 
adaptation.  In  the  first  place,  stimuli  arising  in  any  part  of  the 
body  may  affect  the  vascular  system  in  two  directions,  causing  reflexly 
dilatation  of  blood-vessels  in  the  part  which  is  the  origin  of  the 
impulses  and  constriction  of  the  blood-vessels  in  the  rest  of  the  body, 
so  that  a  normal  or  raised  blood  pressure  is  available  for  driving 
an  increased  supply  of  blood  through  the  dilated  vessels  of  the  part. 
Thus,  if  both  hind  limbs  of  an  animal  be  placed  in  a  plethysmograph, 
it  w\\\  be  seen  that  stimulation  of  the  anterior  crural  or  peroneal  nerve 
in  the  left  leg  causes  dilatation  of  this  leg  and  constriction  of  the 
leg  of  the  other  side.  At  rest  the  organs  of  the  chest  and  abdomen 
contain  more  than  half  of  the  total  quantity  of  blood  in  the  body,  so 
that  very  little  change  in  the  capacity  of  these  organs  suffices  to 
furnish  the  extra  supply  of  blood  needed  by  any  part  during  a  state 
of  increased  activity. 

Another  factor  which  is  possibly  involved  in  the  production  of  the 
increased  blood-flow  through  active  organs  is  a  chemical  stimulation 
of  the  vessels  themselves,  by  means  of  substances  (metabolites)  pro- 
duced as  a  result  of  the  chemical  changes  accompanying  activity. 
The  great  increase  in  the  flow  through  the  muscles  which  accom- 
panies muscular  exercise  is  probably  brought  about  largely  by  this 
means.  It  has  been  shown  that  the  passage  of  blood  containing 
lactic  acid  or  carbon  dioxide  (both  results  of  muscular  metabolism) 
causes  a  marked  dilatation  of  the  blood-vessels  of  a  limb.  The  following 
figures  may  be  given  as  showing  the  influence  of  activity  on  the  blood- 
flow  through  various  organs  : 

Flow  ix  Cubic  Centimetees  per  Minute  per  100  Grm.  Tissue 


At  rest 

Active 

Levator  labii  superioris  (of  the  horse) 

17-5 

85 

Kidney      ...... 

— 

140 

Hind  limb          ..... 

3-4 

— 

Hind  limb  (after  section  of  nerves) 

9-9 

— 

Thyroid  gland    ..... 

590-0 

— 

Rabbit's  brain  ..... 

1360 

— 

SECTION  XII 

THE  INFLUENCE  ON  THE  CIRCULATION  OF 
VARIATIONS  IN  THE  TOTAL  QUANTITY  OF 

BLOOD 

PLETHORA  AND  HYDREMIC  PLETHORA 

The  effects  of  increasing  the  total  volume  of  circulating  fluid  may 
be  studied  by  injecting  several  hundred  cubic  centimetres  of  defi- 


260  - 
250- 
240- 
230  - 
2?0  - 
210  . 
200 
190  - 
180  •■ 
170  - 
160- 
(50- 
140- 
130- 

... 

,    :     :     :     '     i   /21Q 1 2^0 ;  290  i  Z20  i  71q'^^    :    i     :     —     ;     ^         '     :     :    i     i    i     :     :    i 

-4-j- 
4.£;4 

4.. .4...;.. 
4.4.-4.. 

\ l__J_ 

.4 4-->4- 

■-* -♦ *- 

:4;4:M4::!44jl!i 
;:tfp:4:i!p:4::ti:: 

- 

... 

— 

4q4:j:tjq5:^4=tittt444:^ 

-4---r-''4-T-|-T--T-4--i--|--f-|---;--i--T-4--j--i"4--t--i--f-4 

:4:4q:in:fifffi-Ji^ 

J20  - 
no  - 
100  - 

90- 

80 

70- 

60  - 

..•...'4..\..},..X-X-\—i..i..i..\... 

::tdi:iH:i±tit:l::: 

4J^.i.4-i-l-i-i-4-i-4.4-., 

■liar 

[|ilTi^i~:1iii'i!:il!^rr 

50- 
40- 
70  -' 

/  1  4    :    ■    '  1    ;    '4    ;  4 
...  ..J..J-.I.4..L.L4..L. L..!   . 

-T-]-4-4--r4--— r-r-r-7-t-4-4-r-^-|-4"4"r~|  ""r 

,..j..u..4-j...4—;-;.-4— 4-4— i—!—4..a-.J.-a..j...4..4-..4— 4.-4— |. 

..4.-'..i--4--4--*--4--'---l— +-i '-- 

1     !     1 

90 

'     i      '      '     -!-    ^-   i-  i-    i      '      i-    -i  -1 

-i    J    1.  i  i    i   4    4    4    l.J    .l_J    4    4-144    4-4  -4     '     I 

j    1 

10 

/ntmvMO}/s\  /^/ei;^  oA  500  parm, 

sa/'.    \    r  1    11:14:    !    1  1"TT  I    1   T4-4--T-4 

!    i 

:    ;    ! 

:     1 

;    :    ! 

)  3 

0  60  SEC           1     1     1          1 

1     1     1     1     1     1     1     1     1     1     1     1 

1        1 

9      10     II      12      B     1^     15     16     17      18        21     22 


Fig.  475.  Effects  of  hydraemic  plethora  on  the  pressures  in  the  carotid  artery 
(thick  line),  portal  vein  (thin  line),  and  inferior  vena  cava  (dotted  line). 
(B.vYLiss  and  Stabling.) 

The  arterial  pressure  is  in  mm.  Hg.  ;   the  venous  pressures  in  mm.  H.^O. 


brinated  blood  or  normal  saline  fluid  into  a  vein.  In  the  latter  case, 
since  the  blood  is  rendered  more  dilute,  the  condition  is  called  hydrae- 
mic plethora  (Fig.  475).  On  the  arterial  pressure  the  result  of  such  an 
injection  is  not  very  marked.  There  is  a  slight  initial  increase  in  the 
pressure,  but  the  increase  is  by  no  means  proportional  to  the  amount  of 

1129 


1130 


PHYSIOLOGY 


fluid  injected,  showing  that  the  fluid  is  not  to  any  large  extent  con- 
tained in  the  arterial  system.  On  examining  the  pressure  in  the  veins, 
however,  we  find  a  very  great  relative  rise  of  pressure,  and  on  opening 
the  abdomen  it  is  seen  that  all  the  veins  are  distended  and  that  the  liver 
is  swollen.  The  effect  of  increasing  the  volume  of  circulating  fluid  would 
be  to  increase  the  mean  systemic  pressure,  and  therefore  one  would 


Systole 


Diastole 


Seconds 


Fig.  476.  Cardiometer  tracing  from  dog's  heart  to  show  effect  of  increasing 
the  volume  of  circulating  blood  (hydrsemic  plethora)  on  the  total  output 
and  the  volume  of  the  heart.  Between  the  parts  A  and  B  30  c.c.  of 
warm  normal  salt  solution  were  injected  intravenously,  and  between  B 
and  c  20  c.c.  more.  It  will  be  noticed  that  both  the  systolic  and  the 
diastolic  volume  are  increased,  i.e.  the  heart  is  more  distended  during 
diastole,  and  does  not  contract  to  its  normal  size  in  systole.  The  con- 
traction volume,  and  therefore  the  output,  are  very  largely  increased. 
(Roy.) 

expect  to  find  a  large  increase  both  in  arterial  and  venous  systems. 
But  the  organism  prevents  the  rise  on  the  arterial  side  by  relaxing  the 
whole  system  of  arterioles,  so  that  the  distribution  of  pressures  is 
altered,  and  the  venous  approximates  more  closely  to  the  arterial 
pressure.  This  arterial  dilatation  augments  the  velocity  of  the  blood  : 
it  has  been  found  that  the  velocity  may  be  accelerated  to  six  or  eight 
times  the  normal  rate  by  injecting  an  amount  of  salt  solution  equiva- 
lent to  50  per  cent,  of  the  total  blood. 

The  high  venous  pressure  causes  increased  diastolic  filling  of  the 


VARIATIONS  IN  TOTAL  QUANTITY  OF  BLOOD      ]  i;,l 

heart,  and  therefore  augments  both  strength  and  frequency  of  the 
beat.     Thus  the  work  of  the  heart  is  increased  in  three  ways,  viz.  by  ; 

(1)  Rise  of  arterial  pressure. 

(2)  Greater  frequency  of  beat. 

(3)  Increased  output  at  each  beat  (Fig.  476). 

These  series  of  changes  result  in  the  relief  of  the  vascular  system. 
The  heightened  pressure  in  the  abdominal  veins  and  capillaries 
causes  a  great  leakage  of  fluid  in  the  form  of  lymph  from  the  capil- 
laries of  the  intestines  and  liver,  while  the  increased  pressure  and 
velocity  of  the  blood  in  the  glomeruli  of  the  kidney  induce  a  copious 
secretion  of  urine,  so  that  within  a  couple  of  hours  after  the  injection 
of  salt  solution  the  volume  of  the  circulating  fluid  may  have  returned 
to  normal. 

This  recovery  is  effected  with  greater  difficulty  if  the  plethora  has 
been  brought  about  by  the  injection  of  defibrinated  blood,  since  this 
fluid  cannot  escape  rapidly  from  the  capillaries,  nor  can  it  be  excreted 
unchanged  by  the  kidneys.  Hence  it  is  easy  to  kill  an  animal  by 
wearing  out  its  heart,  if  too  large  quantities  of  defibrinated  blood  be 
injected.  The  ultimate  fate  of  the  injected  blood  is  to  be  used  as  food 
by  the  tissues,  and  to  be  eliminated  by  the  ordinary  channels. 

It  must  be  remembered  that  the  blood-serum  of  one  animal  is  often  poisonous 
for  the  corpuscles  of  another.  Thus  a  few  cubic  centimetres  of  dog's  serum 
injected  into  the  peritoneal  cavity  of  a  rabbit  will  cause  death.  This  poisonous 
action  is  also  shown  by  mixing  dog's  serum  with  defibrinated  rabbit's  blood,  in 
which  case  the  red  corpuscles  of  the  latter  are  broken  up,  setting  free  haemoglobin 
(hcemolysis). 

THE  EFFECTS  OF  HAEMORRHAGE.  ANAEMIA 
Any  diminution  of  the  total  volume  of  the  blood,  as  by  bleeding, 
would  tend  to  lower  the  pressure  on  both  sides  of  the  system.  The 
vaso-motor  centre,  however,  strives  to  maintain  a  normal  arterial 
pressure,  and  so  the  circulation  through  the  brain,  unaltered.  This 
object  is  carried  out  by  a  general  vascular  cojistriction,  which  diminishes 
the  total  capacity  of  the  system  and  alters  the  distribution  of  pressures 
throughout  the  system,  so  as  to  keep  the  blood  as  much  as  possible 
on  the  arterial  side.  Thus  a  slight  loss  of  blood  has  no  influence 
on  the  arterial  blood  pressure,  but  causes  a  fall  of  pressure  in  the 
veins,  blanching  of  the  abdominal  organs,  and  diminished  flow  of  urine. 
The  heart  beats  very  frequently,  and  so  aids  in  emptying  the  venous  into 
the  arterial  system. 

Tiie  deficiency  of  circulating  fluid  caused  by  bleeding  is  soon 
remedied  by  a  transfer  of  fluid  from  the  tissues  to  the  blood.  This 
transfer  is  independent  of  the  flow  of  lymph  from  the  thoracic  duct 
into  the  blood,  and  is  the  direct  consequence  of  the  universal  fall  of 


1132  PHYSIOLOGY 

capillary  pressure  which  results  from  the  bleeding.  The  abstraction 
of  fluid  from  the  tissues  is  responsible  for  the  extreme  thirst  which  is 
the  result  of  hsemorrhage.  and  which  directs  the  animal  to  take  up  by  the 
alimentary  canal  the  fluid  which  is  wanting  to  the  body.  The  transfer 
of  fluid  from  tissues  to  blood  is  extremely  rapid  ;  even  during  the 
course  of  a  bleeding  it  is  found  that  the  later  samples  of  blood  are 
more  dilute  than  those  obtained  at  the  beginning.  This  mechanism 
suffices  only  to  make  up  the  supply  of  circulating  fluid.  After  a 
bleeding,  however,  an  animal  has  lost  proteins  and  blood-corpuscles, 
and  these  constituents  of  the  blood  are  but  slowly  restored,  the  former 
directly  from  the  food,  the  latter  by  an  increased  activity  of  the  blood- 
forming  cells  in  the  red  marrow. 


CHAPTER  XIV 

LYMPH  AND  TISSUE  FLUIDS 

In  no  part  of  the  body  does  the  blood  come  in  actual  contact  with 
the  hving  cells  of  the  tissue.  In  all  parts  the  blood  flows  in  capillaries 
with  definite  walls  consisting  of  a  single  layer  of  cells,  and  is  thus 
separated  from  the  tissue-elements  by  these  walls  and  by  a  varying 
thickness  of  tissue.  In  some  organs,  such  as  the  liver  and  lung,  every 
cell  is  in  contact  with  the  outer  surface  of  some  capillary  ;  while  in 
others,  such  as  cartilage  (which  is  quite  avascular),  a  considerable 
thickness  of  tissue  may  separate  any  given  cell  from  the  nearest 
capillary.  A  middleman  is  thus  needed  between  the  blood  and  the 
tissues,  and  this  middleman  is  the  tissue-fluid  or  lymph  which  fills 
spaces  between  all  the  tissue-elements,  so  that  any  tissue  can  be 
regarded  as  a  sponge  soaked  with  lymph. 

Throughout  these  spaces  we  find  a  close  network  of  vessels  lined, 
and  separated  from  the  tissue  spaces,  by  a  layer  of  extremely  thin 
endothelial  cells,  and  this  plexus  communicates  with  definite  channels 
— lymphatics,  by  which  any  excess  of  fluid  in  the  part  is  drained  off. 
The  lymphatics  all  run  towards  the  chest,  where  those  of  the  limbs  join 
a  large  vessel  (the  receptaculum  chyli),  which  receives  the  IjTiiph  from 
the  alimentary  canal,  to  form  the  thoracic  duct.  This  runs  up  on  the 
left  side  of  the  oesophagus,  to  open  into  the  venous  system  at  the  junc- 
tion of  the  left  internal  jugular  with  the  subclavian  vein.  A  small 
vessel  on  the  right  side  drains  the  lymph  from  the  right  upper 
extremity  and  right  side  of  the  chest  and  neck. 

The  lymph  may  be  looked  upon  as  a  part  of  the  plasma  which 
exudes  through  the  capillary  wall,  bathes  all  the  tissue-elements, 
passes  between  the  endothelial  cells  into  the  peripheral  Ivmphatic 
network,  whence  it  is  carried  by  lymphatic  trunks  into  the  thoracic 
duct,  by  which  it  is  returned  again  to  the  blood. 

It  is  easy  to  obtain  lymph  for  examination  by  putting  a  cannula 
(a  small  tube  of  glass  or  metal)  into  the  thoracic  duct,  and  collecting 
the  fluid  that  drops  from  it  in  a  glass  vessel. 

We  may  also  tap  in  a  similar  way  one  of  the  large  l\Tnphatic  trunks 
of  the  limbs  ;  but  in  the  latter  case  we  have  to  use  artificial  means  to 
induce  a  flow  of  lymph,  since  little  or  none  can  be  obtained  from  a 
limb   at   rest,   the   only  part  of    the    body  where  there  is  normally 

1133 


1134  PHYSIOLOGY 

a  constant  flow  of  lymph  being  the  alimentary  canal.  And  thus 
we  cannot  regard  the  flow  of  lymph  from  a  part  as  any  index 
of  the  chemical  changes  going  on  at  that  part.  In  a  limb  at  rest 
food-stuffs  are  being  taken  up  from  the  blood  and  being  burnt  up  by 
the  muscles  with  the  production  of  CO2,  although  we  may  not  be  able 
to  obtain  a  drop  of  lymph  from  a  cannula  in  one  of  the  lymphatics. 
The  lymph  is  thus  truly  a  middleman  ;  as  any  substance,  oxygen 
or  food-stuff,  is  taken  up  by  a  tissue-cell  from  the  lymph  surrounding 
it,  this  latter  recoups  itself  at  once  at  the  expense  of  the  blood. 
Thus  there  would  seem  to  be  no  need  for  lymphatics  to  drain  the 
limb,  were  it  not  that  under  many  conditions  which  we  shall  study 
directly,  the  exudation  of  lymph  from  the  blood-vessels  is  so  excessive 
that,  if  it  were  not  carried  off  at  once  and  restored  to  the  blood,  it 
would  accumulate  in  the  tissue  spaces,  give  rise  to  dropsy,  and  by 
pressure  on  the  cells  and  blood-vessels  affect  them  injuriously. 

PROPERTIES  OF  LYMPH 

Lymph  obtained  from  the  thoracic  duct  of  an  animal  varies  in 
composition  and  appearance  according  to  the  condition  of  the  animal, 
whether  recently  fed  or  fasting.  From  a  fasting  animal  the  lymph  is 
a  transparent  liquid,  generally  slightly  yellowish,  and  sometimes 
reddish  from  admixture  of  blood-corpuscles.  When  obtained  from 
an  animal  shortly  after  a  meal,  it  is  milky  from  the  presence  of  minute 
particles  of  fat  that  have  been  absorbed  from  the  alimentary  canal. 
In  the  latter  case,  if  the  intestines  be  exposed,  the  small  lymphatics 
are  to  be  seen  as  white  lines  running  from  the  intestine  to  the  attached 
part  of  the  mesentery.  It  is  owing  to  this  fact  that  these  lymphatics 
have  received  the  special  name  lacteals,  the  lymph  in  them  being  called 
the  chyle.    The  fatty  particles  form  the  molecular  basis  of  the  chyle. 

On  microscopic  examination  the  transparent  lymph  of  fasting 
animals  presents  colourless  corpuscles  similar  to  those  of  blood,  or 
perhaps  we  ought  to  say  identical,  since  the  leucocytes  of  the  blood 
are  partly  derived  from  the  corpuscles  that  have  entered  with  the 
lymph  through  the  thoracic  duct. 

All  the  lymphatics  pass  at  some  point  of  their  course  through 
lymphatic  glands,  which  we  may  look  upon  as  factories  of  leucocytes, 
since  these  are  much  more  numerous  in  the  lymph  after  it  has  traversed 
the  gland  than  before.  Leucocytes  are  also  formed  in  all  the  numerous 
localities  where  we  find  adenoid  tissues,  such  as  the  tonsils,  air  passages, 
ahmentary  canal  (Peyer's  patches  and  solitary  follicles),  Malpighian 
bodies  of  the  spleen,  and  thymus. 

The  lymph  from  the  thoracic  duct  is  alkaline,  has  a  specific  gravity 
of  about  1015,  and  clots  at  a  variable  time  after  it  has  left  the  vessels, 
forming  a  colourless  clot  of  fibrin,  just  like  blood-plasma.     It  contains 


LYMPH  AND  TISSUE  FLUIDS  1135 

about  6  per  cent,  of  solid  matters,  the  proteins  consisting  of  fibrinogen, 
paraglobulin,  and  serum  albumen.  The  salts  are  similar  to  those  of 
the  liquor  sanguinis,  and  are  present  in  the  same  proportions. 

THE  PRODUCTION  OF  LYMPH 

Many  physiologists  have  thought  that,  in  the  transudation  of  the  . 
fluid  which  forms  the  lymph,  there  is  an  active  intervention  on  the  ' 
part  of  the  endothelial  cells  forming  the  capillary  wall,  and  that  lymph 
is  therefore  to  be  regarded  as  a  true  secretion.     A  careful  investigation 
of  the  known  experimental  facts  has  failed  to  show  that  the  endo- 
thelial cells  act  other^^^se  than  passively,  as  filtering  membranes  of 
variable   permeability.     The  factors  which  are  responsible  for  the 
transudation  of  lymph  may  be  divided  into  two  classes — mechanical 
and  chemical,  the  former  depending  largely  on  the  pressure  of  the  ^^^ 
blood  in  the  vessels,  and  the  latter  chiefly  on  the  metabolism  of  the 
cells  outside  the  vessels. 

According  to  the  views  here  laid  down,  the  formation  of  lymph 
may  be  compared  to  a  process  of  filtration.  If  this  be  correct 
the  amount  of  lymph  formed  in  any  given  capillary  area  must  be 
dependent  on  the  difference  of  pressure  between  the  blood  in  the 
vessels  and  the  fluid  in  the  extravascular  tissue  spaces.  This  latter 
pressure  is  normally  extremely  low,  so  that  in  attempting  to  test 
the  truth  of  this  view  we  must  try  the  effects  of  altering  the  pressure 
inside  the  vessels,  in  the  expectation  of  finding  that  the  lymph  pro- 
duction will  rise  and  fall  as  the  capillary  pressure  is  increased  or 
diminished.  On  attempting  to  carry  out  such  experiments  in  different 
parts  of  the  body,  we  have  to  recognise  another  factor  besides  the 
capillary  pressure,  viz.  the  permeability  of  the  vessel-wall.  Whereas 
the  capillary  walls  in  the  limbs  and  connective  tissues  generally 
present  a  very  considerable  resistance  to  the  filtration  of  lymph 
through  them,  and  keep  back  the  larger  portion  of  the  proteins  of  the 
blood-plasma,  the  intestinal  capillaries  are  much  more  permeable, 
giving  at  moderate  capillary  pressures  a  continual  flow  of  lymph  and 
separating  off  only  a  small  proportion  of  the  proteins.  It  is  in  the 
liver,  however,  that  we  find  the  greatest  permeability.  Here  a  very 
small  pressure  sufiices  to  produce  a  great  transudation  of  lymph, 
containing  practically  the  same  amount  of  protein  as  the  blood-plasma 
from  which  it  is  formed. 

The  ease  with  which  fluid  passes  out  from  the  capillaries  of  the  Uver  is  probably 
due  to  the  fact  that  these  vessels,  unUko  most  other  capillaries  of  the  body,  have 
not  a  complete  endothelial  lining.  Thus  it  is  impossible  to  display  a  continuous 
endotheUal  lining  by  means  of  silver  nitrate.  The  cells  surrounding  the  capil- 
laries are  large  and  branched,  and  possess  marked  phagocytic  powers,  so  that 
after  an  injection  of  carmine  granules  or  bacteria  into  the  blood-stream  these 
bodies  are  found  in  quantity  within  the  cells.    Owing  to  the  incompleteness  of 


1136  PHYSIOLOGY 

this  investment  the  liver-cells  in  many  places  abut  on  the  lumen  of  the  capillary. 
On  injecting  the  blood-system  of  the  liver  the  injection  is  found  to  run  with  ease 
into  channels  situated  within  the  cells  themselves,  and  it  is  reasonable  to  conclude 
that  the  blood-plasma  takes  the  same  course  through  these  intracellular  channels, 
by  which  it  passes  into  the  lymphatics  which  lie  at  the  periphery  of  the  lobules. 

In  experiments  on  the  lymph  production  in  the  limbs  alterations 
of  capillary  pressure  have  but  slight  effect.  The  lymph-flow  from  a 
limb  lymphatic  is  practically  unaltered  by  changes  in  its  arterial 
supply,  although  a  definite  increase  may  be  obtained  by  ligaturing  all 
the  veins  of  the  limb  so  as  to  cause  a  very  great  rise  of  capillary 
pressure.  The  lymph-flow  from  the  intestines  can  be  measured  by 
collecting  the  lymph  from  the  thoracic  duct.  If  the  lymphatics 
which  leave  the  liver  in  the  portal  fissure  be  previously  ligatured,  the 
whole  of  the  thoracic  duct  lymph  in  an  animal  at  rest  is  derived  from 
the  intestines.  It  will  be  found  that  lowering  of  the  capillary  pressure 
in  these  organs  by  obstructing  the  thoracic  aorta  stops  the  flow  of 
lymph  absolutely,  whereas  a  rise  of  capillary  pressure,  such  as  that 
produced  by  ligature  of  the  portal  vein,  causes  a  four-  or  fivefold 
increase  of  the  lymph. 

The  effect  of  rise  of  capillary  pressure  on  the  lymph-flow  is  still 
more  striking  in  the  case  of  the  liver.  If  the  inferior  vena  cava  be 
obstructed  just  above  the  opening  of  the  hepatic  veins,  there  is  a  great 
fall  of  arterial  pressure,  but,  owing  to  the  damming  back  of  the  blood, 
a  rise  of  pressure  in  the  liver  capillaries  to  three  or  four  times  the 
normal  height.  This  rise  causes  a  large  increase  in  the  lymph-flow 
from  the  thoracic  duct.  The  lymph  may  be  increased  eight  to  ten 
times  in  amount,  and  it  contains  more  protein  than  before.  If  the  portal 
lymphatics  be  previously  ligatured,  obstruction  of  the  inferior  vena 
cava  has  no  effect  on  the  l)anph-flow,  showing  that  the  whole  of  this 
increase  is  derived  from  the  one  region  of  the  body  where  the  capillary 
pressure  is  increased,  viz.  the  liver. 

We  must  conclude  that  in  those  regions  of  the  body  where  the 
capillaries  are  fairly  permeable  the  most  important  factor  in  lymph 
production  is  the  intracapillary  pressure. 

In  the  case  of  the  limbs  and  connective  tissues  generally,  the 
pressure  factor  is  probably,  under  normal  conditions,  of  less  im- 
portance, so  that  the  second  condition,  the  chemical,  comes  here  more 
into  prominence.  The  capillary  wall  not  only  permits  of  filtration 
under  certain  pressures  but  also  allows  the  passage  of  water  and  dis- 
solved substances  by  diffusion  and  osmosis.  These  osmotic  inter- 
changes between  blood  and  cell  through  the  intermediation  of  the 
lymph  are  constantly  going  on  in  the  normal  life  of  the  tissue,  and 
are  quite  independent  of  the  amount  of  lymph  produced.  Thus  a 
gland-cell  may  use  up  oxygen,  calcium,  or  sugar,  and  create  a  vacuum 


LYMPH  ANT)  TISSUE  FLUIDS  1137 

of  these  substances  in  the  layer  of  lymph  immediately  surrounding 
the  cell.  There  is  at  once  a  disturliance  of  the  equilibrium,  and  a  flow 
of  these  substances  from  blood  to  lymph  is  set  up.  In  consequence  of 
the  wonderful  arrangements  in  the  tissues  for  ensuring  the  intimate 
contact  of  blood  and  lymph  without  intermingling,  these  changes  can 
occur  with  gi'eat  rapidity.  We  find,  for  instance,  that  if  a  very  large 
amount  (40  grm.)  of  dextrose  be  injected  into  the  circulation,  osmotic 
equilibrium  between  blood  and  lymph  is  established  within  half  a 
minute  of  the  termination  of  the  injection.  In  this  case  the  rise  of 
osmotic  pressure  caused  by  the  injection  of  the  sugar  attracts  water 
from  the  tissue-fluid,  and  this  in  its  turn  from  the  tissue-cells,  until  the 
osmotic  pressure  inside  and  outside  the  vessels  is  the  same.  By  this 
means  the  volume  of  the  circulating  blood  is  increased  at  the  expense  of 
the  tissues.  A  process  of  this  character  may,  however,  work  under 
normal  circumstances  in  the  reverse  direction,  and  lead  to  a  passage  of 
fluid  from  blood  to  tissues  and  tissue  spaces.  Every  active  contrac- 
tion of  a  muscle,  for  instance,  is  attended  by  the  breaking  down  of  a 
few  large  molecules  into  a  number  of  smaller  ones,  and  this  increase 
in  the  number  of  molecules  causes  a  rise  of  osmotic  pressure  in  the 
muscle  fibre  and  surrounding  lymph,  and  therefore  a  passage  of  fluid 
from  blood  to  lymph.  In  the  same  way  a  cell  of  the  submaxillary 
gland,  when  stimulated  by  means  of  its  nerve,  pours  out  a  quantity  of 
fluid  into  the  gland-duct,  and  so  into  the  mouth.  This  fluid  comes 
in  the  first  instance  from  the  cell  itself,  but  the  cell  recoups  itself 
from  the  surrounding  lymph,  raising  the  concentration  of  this  fluid, 
and  the  difference  in  concentration  thus  caused  at  once  induces  a 
passage  of  water  from  blood  to  Ijonph.  Hence  salivary  secretion 
is  associated  with  a  large  flow  of  fluid  through  the  capillary  walls 
of  the  gland.  In  this  passage  the  endothelial  cells  of  the  capillaries 
play  no  part,  the  whole  process  being  conditioned  by  changes  in  the 
extravascular  gland-cell.  We  have  only  to  paralyse  the  gland-cell 
by  means  of  atropin  in  order  to  see  that  the  active  flushing  of  the 
gland  which  accompanies  activity  produces  merely  a  minimal  increase 
in  the  lymph-flow  from  the  gland. 

The  influence  of  tissue  activity  in  the  production  of  hiiiph  is 
still  better  8ho\NTi  in  the  case  of  a  large  gland,  such  as  the  liver.  Stimu- 
lation of  this  organ  by  the  injection  of  bile  salts  into  the  blood-stream 
causes  a  large  increase  in  the  lymph-flow  from  the  organ,  and  there- 
fore in  the  lymph-flow  from  the  thoracic  duct. 

It  is  important  to  remember  that  the  relative  insusceptibility  of  the 
limb  capillaries  to  pressure  holds  only  for  the  absolutely  normal 
capillary.  Any  factor  which  leads  to  impaired  nutrition  of  the 
vascular  wall,  such  as  deficiency  of  supply  of  blood  or  oxygen,  the 
presence  of  poisons  in  the  blood  or  in  the  surrounding  tissues,  scalding 

72 


1138 


PHYSIOLOGY 


or  freezing,  increases  at  the  same  time  its  permeability.  Under  such 
conditions  the  limb  capillary  reacts  to  changes  of  pressure  like  a  liver 
capillary,  the  slightest  increase  of  pressure  causing  an  appreciable 
increase  in  the  lymph  production.  This  increased  lymph  production 
may  be  too  great  to  be  carried  off  by  the  lymphatic  channels,  so  that 
the  exuded  fluid  stays  in  the  tissue  spaces,  distending  them  and 
causing  the  condition  known  as  oedema  or  dropsy. 

LYMPHAGOGUES.  Among  the  substances  which  have  a  direct 
action  on  the  vessel  wall  are  a  number  of  bodies  which  were  described 
by  Heidenhain  as  lymphagogues  of  the  first  class.  As  their  name 
implies,  these  bodies  on  injection  into  the  blood-stream  cause  an 
increased  flow    of  lymph  from  the   thoracic   duct.      They   may  be 


_j    I  I  I  ii-m^-M-ii'h   Mill 
_a  j_L  iipil  I  ffi.n^  j-Lilii-L-t 

-T4-H-i-^-^-|-+H-Kl-f+-4-|t 


gpmlhutes 


Ini  of  mussel  extract 


Fig.  477.  Changes  in  lymph  flow  in  portal,  inferior  cava,  and  arterial  pres.sures. 
resulting  from  injection  of  a  member  of  the  first  class  of  lymphagogues  (extract 
of  mussels).     (Starling.) 

extracted  from  the  dried  tissue  sof  crayfish,  mussels,  or  leeches  by  simple 
boiling  with  water.  Commercial  peptone  has  a  similar  effect.  Heiden- 
hain regarded  these  bodies  as  direct  excitants  of  the  secretory  activities 
of  the  endothelial  cells.  They  are,  however,  general  poisons,  having 
a  special  action  on  the  vascular  system,  and  their  effect  on  lymph 
production  is  probably  due  simply  to  their  deleterious  action  on  the 
capillary  wall.  Although  these  bodies  act  chiefly  on  the  liver  capil- 
laries, so  that  the  main  increase  in  the  thoracic  duct  lymph  is  derived 
from  the  liver,  they  can  be  shown  also  to  have  some  effect  in  the 
same  direction  on  the  intestinal  and  skin  capillaries.  In  fact  the 
injection  or  ingestion  of  these  bodies  often  gives  rise  to  a  copious  erup 
tion  of  nettle-rash,  i.e.  swelhngs  of  the  skin  due  to  an  increased  exuda- 
tion of  lymph  into  the  meshes  of  the  cutis. 

An  increased  lymph-flow  from  the  thoracic  duct  may  be  produced 
also  by  the  injection  of  large  amounts  (10  to  40  grm.)  of  innocuous 


LYMPH  AND  TISSUE  FLnDS 


1139 


crystalloids,  such  as  dextrose,  urea,  or  sodium  chloride,  intot  he  circu- 
lation. In  this  case  the  lymph  becomes  much  more  dilute.  The 
explanation  of  the  action  of  these  bodies  is  very  simple.  We  have 
already  seen  that  injection  of  large  amounts  of  dextrose  into  the 


60mrnuC.es 


inJoF 40qrams  dextrose 


-r-}-t-^n-T-FP.-,-  ~-~~ — r-r-r^^-^-r-H — •,- 

-.-H .     I     .     I     I — i    I     I     I     I     I     |.  I 


•Jr^W^-^^A  ^y??-J— .  -4.  -«  -(-  - 


■T->-!-r!-i-t-izhr  -M-  t-r  t  ■ 


I  I  I  i  i  I  I  I 


01  234^5678910 


50 


60  minutes 


Bled  to  240  ccm      Inj.  18 grams  dextrose 


Fig.  478.     Effect  on  lymph  flow  and  on  arterial  and  venous  pressures  of  injection 
of  confentrattd  solution  of  glucose. 
In  B  the  animal  was  bled  to  240  c.c.  before  the  injection.     The  double  line 
=  lymph  flow  in  c.c.  per  ten  minutes;  thin  line  =  portal  vein  ;   thick  line  ^ 
carotitl  artery  ;   dotted  line  =  inferior  vena  cava. 

circulating  blood  raises  the  osmotic  pressure  of  this  fluid.  The  blood 
therefore  imbibes  water  from  the  tissues  and  swells  up,  i.e.  a  con- 
dition of  hydra?mic  plethora  is  brought  about  as  surely  as  if  several 
hundred  cubic  centimetres  of  normal  salt  solution  were  injected  into 
the  circulation.  This  increase  in  the  total  volume  of  the  blood  causes 
a  rise  of  pressure  throughout  the  vascular  system — arteries,  capillaries, 


1140  PHYSIOLOGY 

and  veins — and  the  increased  capillary  pressure,  combined  with  the 
watery  condition  of  the  blood,  induces  a  great  transudation  of  lymph, 
especially  in  the  abdominal  organs  (Fig.  478).  The  lymph  is  more 
watery  because  the  blood  also  is  diluted.  That  the  action  of  these  bodies 
is  purely  mechanical  is  shown  by  the  fact  that,  if  the  rise  of  capillary 
pressure  be  prevented  by  bleeding  the  animal  immediately  before  the 
injection,  the  increase  in  the  lymph-flow  is  also  prevented  (Fig.  478,  b), 
although  the  concentration  of  the  sugar  or  salt  in  the  blood 
is  still  greater  than  in  the  experiments  in  which  bleeding  was  not 
performed. 

MOVEMENT  OF  LYMPH 

In  the  frog  the  circulation  of  lymph  is  maintained  by  rhythmically 

contracting  muscular  sacs,  which  are  placed  in  the  course  of  the  main 

ymph- channels,  and  pump  the  lymph  into  the  veins.     In  the  higher 

animals  and  in  man  the  onward  flow  of  lymph  is  effected  partly  by 


^^ll'lVM 


Flo.  47f).     A  lymphatic  vessel  Laid  open  to  show  arrangement  of  the 
valves.     (Testut.) 

the  pressure  at  which  it  is  secreted  from  the  capillaries  into  the  inter- 
stices of  the  tissues,  but  also  to  a  large  extent  by  the  contractions  of 
the  skeletal  muscles.  In  the  smaller  lymph-radicles  the  pressure  of 
lymph  may  attain  8  to  10  mm.  soda  solution.  In  the  thoracic  duct, 
at  the  point  where  it  opens  into  the  great  veins  of  the  neck,  the  pres- 
sure is  obviously  the  same  as  in  these  veins,  that  is  to  say,  from  —  4  to 
0  mm.  Hg,  the  negative  pressure  being  occasioned  by  the  aspiration  of 
the  thorax.  This  difference  of  pressure  is  sufficient  to  cause  a  certain 
amount  of  flow.  It  must  be  remembered,  however,  that  under  normal 
circumstances  no  lymph  at  all  flows  from  a  resting  limb.  The  only 
part  of  the  body  which  gives  a  continuous  stream  of  l}inph  during  rest 
is  the  alimentary  canal,  the  lymph  in  which  is  poured  out  into  the 
lacteals,  and  thence  makes  its  way  through  the  thoracic  duct.  Move- 
ment, active  or  passive,  of  the  limbs  at  once  causes  a  flow  of  lymph  from 
thom.  Since  the  lymphatics  are  all  provided  with  valves  (Fig.  479), 
the  efiect  of  external  pressure  on  them  is  to  cause  the  lymph  to  flow 
in  one  direction  only,  i.e.  towards  the  thoracic  duct  and  great  veins. 
Hence  we  may  look  upon  muscular  exercise  as  the  greatest  factor 
in  the  circulation  of  lymph.  The  flow  of  lymph  from  the  commence- 
ment of  the  thoracic  duct  in  the  abdominal  cavity  to  the  main  part  of 


LYMPH  AND  TISSl"^  FLUIDS  1141 

it  in  the  thoracic  cavity  is  materially  aided  by  the  respiratory  move- 
ments ;  since,  with  every  inspiration,  the  lacteals  and  abdominal  part 
of  the  duct  are  subjected  to  a  positive  pressure,  and  the  intrathoracic 
part  of  the  duct  to  a  negative  pressure,  so  that  lymph  is  continually 
being  sucked  into  the  thorax. 

THE  ABSORPTION  OF  LYMPH  AND  TISSUE  FLUIDS 
On  injecting  a  coloured  solution  or  suspension  into  the  connective 
tissues  of  any  part  of  the  body,  and  gently  kneading  the  part,  it  is  found 
that  the  fluid  fills  all  the  lymphatic  channels  running  from  the  part ; 
and  we  can  in  this  way  inject  the  lymphatics  of  the  limb  and  trace  their 
course  on  to  the  thoracic  duct.  The  same  path  is  taken  by  micro- 
organisms as  .they  spread  in  the  tissues,  or  by  particles  of  carmine 
or  Indian  ink  which  have  been  introduced  in  tattooing.  It  is  on  account 
of  these  facts  that  the  lymphatics  are  often  spoken  of  as  the  '  absorbent 
system.' 

This  process  of  lymphatic  absorption  is,  however,  a  slow  one, 
unless  aided  to  a  large  extent  by  passive  or  active  movements  of  the 
siu-rounding  parts,  and  cannot  therefore  account  for  the  rapid  symp- 
toms of  poisoning  which  supervene  Anthin  two  or  three  minutes  after 
the  hypodermic  injection  of  a  solution  of  strychnine  or  other  poison. 
That  this  absorption  is  not  dependent  on  the  lymphatics  is  shown 
by  the  fact  that  the  symptoms  occur  almost  as  quickly  when  all  the 
tissues  of  the  limb  have  been  severed  with  the  exception  of  the  main 
artery  and  vein.  In  the  same  way,  after  injecting  methylene  blue  or 
indigo  carmine  into  the  pleural  cavity  or  subcutaneous,  tissues,  the 
dyestufE  appears  in  the  urine  long  before  any  trace  of  colour  can  be 
perceived  in  the  lymph  flowing  from  the  thoracic  duct.  The  absorption 
in  these  cases  is  by  the  blood-vessels,  and  consists  in  an  interchange 
between  blood  and  extra  vascular  fluids,  apparently  dependent  entirely 
upon  processes  of  difiusion  between  these  two  fluids.  So  long  as  any 
diiference  in  composition  exists  between  the  intra-  and  extra  vascular 
fluids,  so  long  will  diffusion-currents  be  set  up,  tending  to  equalise  this 
difference. 

More  difficulty  is  presented  by  the  question  of  the  mechanism  of 
absorption  by  the  blood-vessels  of  the  normal  tissue  fluids — such  an 
absorption  as  we  have  seen  to  occur  after  loss  of  blood  by  hiemorrhage. 
It  seems  probable  that  this  absorption  depends  on  tlie  small 
proportion  of  protein  contained  in  the  tissue  fluid  as  compared  with 
the  blood-plasma,  and  is  due  to  the  Of?m«>tic  pressure  of  the 
protein.  If  blood-serum  be  placed  in  a  bell-shaped  vessel  (the 
mouth  of  which  is  closed  by  a  gelatinous  membrane  whicli  does  not 
permit  the  passage  of  protein),  and  suspended  in  normal  salt  solution, 
it  is  found  that  the  serum  absorbs  the  salt  solution  until  the  manometer 


1142  PHYSIOLOGY 

attached  to  the  bell-jar  indicates  a  pressure  of  25-30  mm.  Hg.  Thus 
we  may  conceive  that  there  is  normally  a  balance  in  the  capil- 
laries between  the  processes  of  exudation  and  of  ab.sorption,  the 
former  being  conditioned  by  the  capillary  blood  pressure  and  the 
latter  by  the  difEerence  in  protein  content,  and  therefore  of  osmotic 
pressure  between  the  blood-plasma  and  tissue-lymph.  A  rise  of 
capillary  pressure  will  upset  this  balance  in  favour  of  transudation 
and  the  blood  will  become  more  concentrated,  whereas  a  fall  of  pressure 
will  turn  the  scale  in  favour  of  absorption  and  the  volume  of  blood 
will  be  increased  at  the  expense  of  the  tissue  fluids. 

THE  PART  PLAYED  BY  THE  LYMPH  IN  THE  NUTRITION 
OF  THE  TISSUES 

The  fact  that  the  tissue-cells  are  separated  by  the  Ijrmph  and  the 
capillary  wall  from  the  blood  shows  that  in  all  interchanges  between  the 
blood  and  tissues  the  lymph  must  act  as  the  medium  of  communication. 
The  lymph-flow  plays  very  little  part  in  this  process.  The  muscles 
of  a  resting  limb  are  taking  up  nourishment  as  well  as  oxygen 
from  the  blood  and  giving  off  their  waste  products — carbonic  acid 
and  ammonia,  though  not  a  drop  of  lymph  may  flow  from  a  cannula 
placed  in  a  lymphatic  trunk  of  the  limb.  In  fact  the  interchange  of 
material  between  tissue-cell  and  blood  through  the  mediation  of  the 
lymph  is  carried  out  in  the  same  way  as  are  the  gaseous  interchanges, 
viz.  by  a  process  of  diffusion.  This  explanation,  however,  holds  good 
only  for  the  difiusible  constituents  of  the  blood  and  will  not  account 
for  the  supply  of  the  indifiusible  protein  molecules  to  the  cell.  Ap- 
parently the  only  way  in  which  the  tissues  can  obtain  their  supply 
of  protein  is  from  the  small  proportion  of  this  substance  which  has 
filtered  through  the  vessel  wall  into  the  lymph.  The  increased 
exudation  of  concentrated  Ijrtiph  to  the  tissues  which  occurs  in 
inflammatory  conditions  or  as  the  result  of  injury  is  therefore  of 
advantage,  since  it  furnishes  an  abundant  supply  of  protein  food  to 
be  used  up  in  the  regeneration  of  the  damaged  cells. 


CHAPTER  XV 

THE  DEFENCE  OF  THE  ORGANISM  AGAINST 
INFECTION 

SECTION  I 

THE  CELLULAR   MECHANISMS   OF   DEFENCE 

One  of  the  main  distinctions,  perhaps  the  most  important,  between 
the  animal  and  vegetable  kingdoms  lies  in  the  inability  of  animals  to 
build  up  their  tissues  at  the  expense  of  inorganic  salts,  and  especially 
to  synthetise  the  various  groups  necessary  for  the  formation  of  the 
protein  molecule.  They  are  thus  rendered  dependent  on  the  assimila- 
tive powers  of  the  vegetable  kingdom,  and  have  to  supply  their 
needs  by  using  the  members  of  this  kingdom  as  food.  The  protozoa, 
for  example,  subsist  largely  on  bacteria.  To  obtain  a  pure  culture 
of  any  form  of  amoeba  it  is  necessary  to  cultivate  this  along  with  some 
form  of  bacteria.  The  power  of  the  unicellular  animals  to  digest  ^ 
bacteria  meets  with  a  response  on  the  part  of  the  latter,  many  of  them 
developing,  by  way  of  self-defence,  the  habit  of  forming  and  excreting 
poisons  which  will  deter  the  amoeba  from  taking  them  up  or  injure  it 
after  it  has  ingested  them.  There  is  thus  a  continuous  struggle  among 
the  various  grades  of  unicellular  organisms  in  which  sometimes  one, 
sometimes  another  type  survives.  An  amoeba  placed  in  contact 
with  most  kinds  of  bacteria,  living  or  dead,  will  rapidly  englobe  and 
digest  them.  There  is,  however,  a  small  organism  known  as  micro- 
sphera  which  is  taken  up  by  the  amoeba,  but  is  not  thereby  destroyed. 
Retaining  its  vitality,  it  reproduces  itself  rapidly  in  the  body  of  its 
host  and  finally  leads  to  disintegration  of  the  latter.  In  the  same 
way  the  flagellate  protozoa  are  often  infected  by  a  species  of  fungus 
known  as  chytridium,  and  die  in  consequence. 

The  liability  of  organisms  to  infection  by  others  endeavouring 
to  live  a  parasitic  existence  at  their  expense  extends  throughout  the 
whole  of  the  animal  and  vegetable  kingdoms.  In  some  cases  the 
host  and  the  parasite  arrive  at  a  compromise  in  whicii  ouch  benefits 
the  other.  This  condition  is  known  as  symbiosis.  We  hav^e  examples 
of  it  in  the  union  of  fungi  and  algie  which  occurs  in  lichens  ;  in  the 
association  of  nitrogen-fixing  bacteria  with  many  plants,    eapecially 

1143 


1144  PHYSIOLOGY 

those  beionging  to  the  natural  order  Leguminosse.  In  herbivorous 
animals  the  presence  of  specific  bacteria  in  the  paunch  or  caecum 
causes  the  breakdown  of  the  cellulose  walls  of  the  food  and  may 
indeed  lead  to  a  building  up  of  protein  from  amino-acids  or  even  from 
salts  of  ammonia.  It  is  probable  that  in  these  cases  the  animal  is 
decidedly  benefited  from  the  presence  of  these  bacteria  in  its 
alimentary  canal,  so  that  here  also  we  may  speak  of  a  symbiosis.  In 
most  cases  invasion  of  a  higher  animal  or  plant  by  some  lower  organism 
is  fraught  with  danger  to  the  host,  so  that  special  mechanisms  have 
to  be  provided  for  the  protection  of  the  tissues  from  infection.    The 


^  Fiti.  480.      A,  aiuceba.  infected  by  Micros phcera:  a,  early  stage.     B,   a  dying 
amoeba,  full  of  parasitic  Micros-phceroE.     (Metchnikoi'f.) 

most  primitive  means  of  defence,  and  one  which  is  found  through- 
out the  whole  animal  kingdom,  is  exactly  analogous  to  the  process 
by  which  the  amoeba  destroys  and  utilises  any  bacteria  present 
in  its  environment.  The  prevention  of  infection  is  of  course  the 
function  of  the  external  layers  of  the  organism,  i.e.  the  epithelial 
covering,  either  of  the  skin  or  of  the  surface  of  the  gut.  Protection 
here  may  be  of  a  physical  or  chemical  character.  The  cells  may 
secrete  a  horny  or  chitinous  layer  which  presents  a  mechanical 
obstruction  to  the  entry  of  bacteria.  They  may  secrete  mucin,  which 
entangles  and  hinders  the  movements  of  invading  micro-organisms,  or 
they  may  secrete  substances  which  actually  destroy  the  life  of  such 
organisms.  When,  however,  a  micro-organism  has  obtained  entrance 
to  the  interior  of  the  body,  e.g.  through  a  wound  of  the  surface  epithe- 
lium, the  task  of  dealing  with  the  invader  becomes  the  office  of  a 
special   type  of  cells   belonging  to   the  inesoblast.     These    cells  are 


THE  CELLULAR  MEOHANLSMS  OF  DEFENCE        1  U5 

similar  in  character  to  the  amoeba.  They  have  the  power  of  extruding 
pseudopodia,  of  wandering  from  place  to  place,  and  of  englobing  and 
digesting  particles  of  food  from  bacteria  with  which  they  come  in  con- 
tact. On  account  of  these  latter  properties  they  have  been  called 
by  Metchnikoft"  phagoci/tes,  and  the  whole  process  by  which  foreign 
material  or  the  animal's  own  dead  tissues  are  got  rid  of  is  spoken  of 
as  phagocytosis.  The  process  can  be  well  studied,  as  has  been  shown 
by  Metchiiikoff,  in  the  sponge  or  in  the  larva  of  the  echinoderm.  At 
one  stage  in  the  development  of  the  latter  the  larva  consists  of  a  sack 
which  is  involuted  at  one  extremity  to  form  the  alimentary  cavity, 


Fig.  481.  1,  gastiula  stage  of  staifisli  embryo,  with  a  foreign  substance,  pi,  in  its 
body  cavity  ;  end,  cndodcrm  ;  ect,  ectoderm  ;  mes,  wandering  mcsoblastic 
cells.  2,  the  foreign  body  of  1,  surroimded  by  a  plasmodium  of  phagocytes 
(highly  magnified).     (After  MiiTCUNiKOFF.) 


while  the  mesoblast  is  represented  by  amoeboid  cells  suspended  in  a 
semi-liquid  substance  filling  the  body  cavity.  If  a  particle  of  foreign 
substance  be  introduced  into  the  body  cavity  the  wandering  mesoderm 
cells  collect  round  the  particle  and  fuse  into  plasmodial  masses,  thus 
forming  a  wall,  as  it  were,  around  it.  If  bacteria  be  introduced,  the 
phagocytes  may  be  seen  to  adhere  to  and  ingest  the  still  living  bacteria, 
which  are  then  rapidly  digested  and  destroyed.  A  similar  process 
may  be  observed  in  the  transparent  crustacean  known  as  the  water- 
flea  (Daphnia),  and  here  it  may  be  noted  that  the  process  of  phago- 
cytosis is  not  always  successful  in  maintaining  the  health  or  life  of  the 
host.  Thus  if  the  spores  of  a  yeast-like  organism,  the  Mothospora,  be 
introduced  into  the  body  cavity  of  Daplmia,  the  leucocytes  may,  if 
the  spores  be  few  in  number,  lay  hold  of  the  latter  and  digest  them. 
If  the  spores  be  in  excess  the  phagocytes  may  fail  to  ingest  them 
or  may  indeed  be  destroyed  as  soon  as  they  ap|)roach  them.  In  this 
case  the  spores  germinate,  iill  up  the  bod)   cavity,  and  luially  lead 


1146  PHYSIOLOGY 

to  the  death  of  the  host.  The  same  process  of  phagocytosis  may  be 
studied  in  its  simple  form  by  injuring  or  infecting  some  tissue  which 
is  free  from  blood-vessels.  Thus  the  tail  fin  of  an  embryonic  axolotl 
may  be  cauterised  with  silver  nitrate,  or  a  small  c^uantity  of  fluid  con- 
taining carmine  granules  may  be  introduced  by  means  of  a  hypo- 
dermic syringe.  In  either  way  a  certain  number  of  cells  are  destroyed 
and  the  dead  tissue  thereupon  acts  as  a  foreign  body.  As  a  result 
the  wandering  mesoderm  cells  or  leucocytes  move  from  the  surround- 
ing tissues  towards  the  seat  of  the  injury,  and  the  day  after  the  injury 
has  been  inflicted  a  collection  of  leucocytes  can  be  seen,  many  of  which 
contain  particles  of  carmine  or  debris  of  the  destroyed  tissue  which 
they  have  taken  up.  The  cells  finally  wander  5way  from  the  part, 
and  the  destruction  is  made  good  by  the  proliferation  of  the  connec- 
tive tissue-cells  and  of  the  epithelium  immediately  adjoining  the  injury. 
In  the  lowest  types  of  metazoa  it  is  impossible  to  speak  of  more  than 
one  type  of  wandering  mesoderm  cell.  It  is  probable  indeed  that  the 
same  type  of  cell  may  at  one  time  act  as  a  scavenger  and  at  another 
as  the  chief  agent  in  the  formation  of  connective  tissues.  Even  in 
Daphnia,  according  to  Hardy,  only  one  form  of  leucocyte  is  present, 
whereas  in  the  much  more  highly  organised  crayfish,  belonging, 
however,  to  the  same  family,  three  different  types  of  leucocyte  may 
be  distinguished.  These  leucocytes  may  be  present  free  in  the  body 
cavity  or  they  may  form  an  element  of  the  connective  tissues.  With 
the  formation  of  a  closed  vascular  system  many  of  the  wandering 
mesoderm  cells  became  attached  to  this  system,  so  that  we  may 
distinguish  a  group  of  blood  leucocytes  or  phagocytes  and  a  group  of 
connective  tissue  or  body-cavity  leucocytes.  Moreover  by  the  formation 
of  a  blood  vascular  system  all  the  tissues  of  the  body  are  brought  into 
material  relationship  with  one  another,  so  that  distant  parts  may  be 
drawn  upon  to  supply  the  needs  of  any  one  part.  It  is  evident  that 
injury  of  a  tissue  in  a  higher  animal  containing  blood-vessels  will 
involve  more  complex  consequences  than  a  similar  injury  or  infection  of 
the  avascular  tissue  of  an  invertebrate,  and  that  the  accumulation  of 
cells  for  the  defence  of  the  organism  against  invading  microbes  will  be 
much  more  effective  if  the  blood-vessels  participate  in  the  process  so 
that,  by  their  means,  the  phagocytic  resources  of  all  parts  of  the  body 
can  be  drawn  upon  to  ward  off  a  localised  attack.  The  process  of 
phagocytosis  thus,  in  the  higher  animals,  becomes  merged  into  the  more 
complex  series  of  phenomena  to  which  the  term  '  inflammation  '  has 
been  applied.  This  process  can  be  studied  by  observing  the  effects 
of  slight  injury  to  some  transparent  part  of  the  body,  e.g.  the 
frog's  tongue  or  mesentery,  or  the  web  of  the  frog's  foot.  For 
this  purpose  a  small  piece  of  the  skin  of  the  frog's  web  is  snipped 
off  with  tine  curved  scissors,  the  section  being  sufficiently  deep  to 


THE  CELLULAR  MECHANISMS  OF  DEFENCE        1147 

remove  the  skin  witliout  causinj^  haemorrhage.  The  first  effect 
noticed  in  the  immediate  neighbourhood  of  the  injury  is  a  dilatation 
of  the  vessels,  especially  of  the  venules,  with  acceleration  of  the  blood- 
flow.     In  the  course  of  an  hour  the  capillaries  also  become  dilated, 


Fig.  4S2.  InHamcd  mesentery  of  frog,  to  show  margination  of  leueocytes 
in  the  inliamcd  capillaries,  a;  migration  of  leucoeytes,  b ;  escape  of  red 
corpuscles,  c ;  accumulation  of  leucocytes  outside  the  capillaries,  d. 
(From  Adami  after  Ribbert.) 

and  many  capillary  channels,  previously  invisible,  are  now  occupied 
with  blood.  Through  the  dilated  capillaries  there  is  a  rapid  blood- 
stream, the  corpuscles  occupying  the  axis  of  the  vessel,  so  that  there 
is  a  periaxial  layer  of  plasma.  A  little  later  this  acceleration  gives 
place  to  a  slowing  of  the  blood-stream,  and  simultaneously  the  leuco- 
cytes of  the  blood  are  seen  to  be 
adherent  to  the  capillary  wall. 
Apparently  the  latter  becomes  what 
we  may  call  '  sticky,'  the  effect  of 
the  stickiness  being  to  increase  the 
resistance  to  the  passage  of  the  blood 
through  the  vessel  and  also  to  cause 
the  adhesion  of  the  leucocytes  to 
the  wall.  As  the  current  becomes  still  slower  the  distinction  between 
axial  and  peripheral  streams  disappears.  The  corpuscles  are  closely 
packed  together,  the  white  corpuscles  being  predominant  at  the 
margins  of  the  capillary,  where  they  fonu  a  lining  to  the  vessel  (Fig. 
482).  The  next  stage  is  the  emigration  of  the  leucocytes.  Those  may  be 
observed  to  thrust  a  process  through  the  vessel-wall  (according  to 
Arnold  this  process  of  emigration  always  occurs  through  the  stigmata, 
i.e.  the  points  where  the  endothelial  cells  come  in  contact — Fig.  483). 
The  prolongation  enlarges  on  the  outer  side  of  the  vessel,  while  the  por- 
tion of  the  leucocyte  within  the  vessel  becomes  smaller,  so  that  finally 


Fic.    483.     Emigration   of   leucoe3'ted 
through  capillary  wall.     (Akxolo.) 


1148  PHYSTOLOOY 

the  whole  leucocyte  passes  through  and  lies  in  the  lymph  spaces  outside 
the  capillary.  In  the  course  of  five  or  six  hours  all  the  capillaries  and 
small  veins  in  the  neighbourhood  of  the  injury  may  show  a  crowd  of 
leucocytes  along  their  outer  surfaces.  The  use  of  this  emigration 
seems  to  be  to  remove  the  tissue  injured  by  the  primary  lesion.  As 
soon  as  this  is  effected,  regeneration  of  the  injured  tissue  occurs  by  a 
proliferation  of  the  connective-tissue  corpuscles  and  the  epithelium, 
while  the  leucocytes  move  away  and  disappear.  The  essential  phago- 
cytic character  of  the  inflammatory  process  may  be  shown  if  the 
primary  lesion  be  attended  with  infection.  Thus  if  a  small  quantity 
of  the  staphylococcus  be  injected  into  the  subcutaneous  tissue  of  the 
rabbit,  the  vessels  surrounding  the  point  of  injection  within  four  hours 
may  be  found  densely  filled  with  corpuscles.  In  ten  hours'  time 
the  leucocytes  are  present  in  large  numbers  outside  the  vessels,  while 
the  injected  cocci  have  spread  for  some  distance  along  the  lymphatic 
spaces  and,  while  partly  free,  have  been  to  a  large  extent  ingested  by 
the  leucocytes.  In  twenty  hours'  time  the  connective-tissue  fibrils  at 
the  point  of  injection  are  found  to  be  widely  separated  by  the  aggrega- 
tion of  leucocytes.  In  forty-eight  hours'  time  a  well-defined  abscess  is 
produced.  At  the  centre  all  traces  of  previous  connective  tissue  have 
disappeared  and  its  place  has  been  taken  by  a  dense  mass  of  leucocytes, 
many  in  a  state  of  degeneration,  mingled  with  staphylococci,  partly 
within,  partly  outside  the  cells.  The  margin  of  the  abscess  is  formed 
by  connective  tissue  infiltrated  with  living  leucocytes.  A  certain 
number  of  cocci  are  to  be  seen  free  in  the  tissue  outside  this  layer,  but 
in  the  course  of  a  day  or  two  these  free  cocci  disappear,  and  there  is 
thus  a  continuous  layer  of  phagocytes  surrounding  the  abscess  cavity 
and  preventing  any  further  invasion  of  the  body  as  a  whole  from  the 
seat  of  infection.  The  abscess  subsequently  discharges  on  to  the 
exterior  by  a  process  of  necrosis  of  the  superjacent  skin,  and  regenera- 
tion of  tissue  takes  place  in  the  same  manner  as  in  the  more  trivial 
injury.  Inflammation  in  warm-blooded  animals  thus  gives  rise  to 
dilatation  of  vessels  and  increased  vascularity  of  a  part,  to  alteration 
of  the  vessel-wall,  and  therefore  to  increased  effusion  of  fluid.  There 
are  increased  warmth  and  redness  of  the  part  from  the  vascular  dilata- 
tion, swelling  from  the  increased  diffusion  of  lymph,  and  very  often, 
as  a  result  of  the  injury  or  the  swelling  and  the  consequent  involve- 
ment of  sensory  nerves,  pain.  The  four  cardinal  symptoms  of 
infiaiuination,  namely,  rubor,  color,  turyor,  and  dolor,  which  have  been 
described  for  generations  as  typical  of  this  condition,  leave  out  of 
account  altogether  the  phenomenon  which  Waller's  and  Cohnheim's 
observations,  in  the  light  of  the  comparative  studies  of  Metchnikofi, 
have  shown  us  to  be  the  essential  feature  of  the  process,  namely,  phago- 
cytosis, the  accumulation  of  wandering  mesoderm  cells  round  the  seat 


THE  CELLULAR  MErHANISMS  OF  DEFENCE       1149 

of  injury  with  the  objects  of  removing  injured  tissue,  of  destroying 
micro-organisms,  of  protecting  the  body  from  general  infection,  and 
of  preparing  the  way  for  reintegration  of  tissue. 

Prior  to  tlie  work  of  Metchnikoff,  the  changes  in  the  l)lood- vessels 
fettered  the  attention  of  physiologists,  and  the  accumulation  of 
leucocytes  was  regarded  as  secondary  to  these  changes.  Though  the 
alteration  of  the  capillary  wall,  by  permitting  the  adhesion  of  the 
leucocytes,  n\ust  no  doubt  favour  their  emigration  and  their  passage 
from  all  parts  of  the  body  into  the  inflamed  })art,  we  know  that  the 
same  accumulation  of  leucocytes  occurs  in  the  entire  absence  of 
a  vascular  system.  The  movement  of  the  corpuscles  towards  dead 
or  injured  tissue  must  therefore  have  some  other  explanation.  We 
have  abundant  evidence  to  show  that  the  essential  factor  in  this 
aggregation  of  leucocytes  is  their  chemical  sensibility,  and  that 
the  phenomenon  is  simply  one  of  chemiotaxis.  A  capillary  glass  tube 
containing  a  suspension  of  dead  micrococci,  or  peptone,  or  broth 
extracted  from  dead  tissue,  if  introduced  into  the  anterior  chamber 
of  the  eye  or  into  the  subcutaneous  tissue,  is  found  after  a  short  time 
to  be  full  of  leucocytes.  We  must  assume  that  the  chemical  products 
diffusing  out  of  the  ends  of  the  capillary  tube  have  acted  like  the  malic 
acid  discharged  by  the  cells  forming  the  female  organ,  the  arche- 
gonium,  of  ferns.  Just  as  the  latter  causes  a  movement  of  the  anthero- 
zoids,  the  male  cells,  towards  the  o^^de,  so  the  chemical  substances 
diffusing  from  the  capillary  tube  have  occasioned  a  positive  chemio- 
taxis on  the  part  of  the  leucocytes.  It  is  worthy  of  note  that  the 
positive  chemiotactic  influence  exerted  by  any  given  species  of  patho- 
genic bacterium  is  roughly  inversely  proportional  to  its  virulence. 
A  culture  lacking  in  virulence  may  cause  a  very  pronounced  aggrega- 
tion of  leucocytes  which  speedily  ingest  and  destroy  the  micro- 
organism, whereas  if  a  culture  of  a  more  virulent  variety  of  the  same 
microbe  be  injected,  there  may  be  all  the  signs  of  inflammation, 
swelling,  and  large  effusion  of  fluid,  but  the  tissues  may  contain  very 
few  leucocytes.  Under  these  circumstances  the  micro-organism 
rapidly  proliferates  and  spreads  from  the  seat  of  the  lesion,  giving  rise 
finally  to  general  infection. 

So  far  we  have  spoken  merely  of  leucocytes  or  phagocj'tes.  and 
have  not  attempted  to  distinguish  between  the  parts  played  by  the 
various  types  of  leucocyte  which  are  found  in  the  blood  and  con- 
nective tissues.  In  the  higher  animals  there  are,  however,  very  many 
varieties  of  leucocytes  belonging  partly  to  the  blood,  partly  to  the  con- 
nective tissues.  The  following  Table,  modified  from  Adami,  enu- 
merates the  leucocytes  which  may  be  concerned  with  inflammation  in 
a  mammal  or  man  : 


1150 


PHYSIOLOGY 


Polymorphonuclear  (polynuclear.  fuiely 
granular  oxj'phile,  neutrophile,  or 
amphophile  cell). 

Eosinophile  (coarsely  granular  oxyphile, 
raacroxycyte). 

Lymphocj'te  (?  of  two  tj'pe.s). 

Plasma-cell  (?  histogenous). 

Endothelioid  leucocyte  (mononiiclear 
leucocji:<?,  hyaline  cell  (in  part),  '  epi- 
thelioid cell  '(in  part). 

Connective  tissue  wandering  cell  (in- 
cluding clasmatocyte). 


Originating  in  adult  mammals  from 
the  bone  marrow,  and  migrating 
from  the  blood  into  the  inflam- 
matory area. 

Originating  from  lymphoid  tissue  and 
from  vascular  and  other  endothelia 
respectively  ;  present  in  inflamed 
area  either  by  migration  from  blood 
or  as  residt  of  local  proliferation. 

Originating  locally  as  result  of  tissue 
proliferation. 


The  part  played  by  each  of  these  forms  is  still  to  a  large  extent 
the  subject  of  discussion.  There  is  no  doubt  that  in  all  active 
inflammations  the  polymorphonuclear  leucocyte  is  the  form  which 
is  attracted  first  and  in  largest  numbers  to  the  seat  of  injury.  It 
is  the  characteristic  cell  from  which  pus  is  formed,  and  is  actively 
phagocytic.  It  has  nothing  to  do  with  the  regeneration  of  the 
destroyed  tissue.  The  eosinophile  corpuscle  is  also  present  at  an 
early  stage  around  the  inflammatory  focus,  but  is  never  present  in 
numbers  at  all  comparable  with  those  of  the  polymorphonuclear 
leucocyte.  It  is  especially  abundant  in  chronic  inflammations  of 
certain  tissues,  such  as  the  skin.  According  to  Kanthack  and  Hardy, 
these  cells  discharge  their  granules  into  the  surrounding  fluid,  render- 
ing this  fluid  toxic  for  bacteria.  Although  later  observations  have 
failed  to  confirm  these  views,  no  other  satisfactory  explanation  has 
been  given  as  to  the  part  played  by  these  cells.  They  are  rarely  seen 
to  ingest  bacteria  and  therefore  cannot  be  spoken  of  as  phagocytic. 
The  lymphocyte  predominates  in  certain  chronic  inflammations, 
especially  in  those  caused  by  the  tubercle  bacillus.  They  do  not  ingest 
bacteria.  The  histogenous  wandering  cells  appear  in  the  inflam- 
matory area  at  a  later  period  than  the  polymorphonuclear  and  eosino- 
phile cells.  They  are  actively  phagocytic  and  are  motile.  As  a  rule 
their  phagocytic  properties  are  exerted,  not  on  bacteria,  but  on  other 
cells  and  cell-debris.  After  an  acute  inflammation  their  chief  office 
is  to  clear  away  the  remains  of  the  polymorphonuclear  leucocytes  and 
dead  tissues  so  as  to  prepare  the  way  for  subsequent  regeneration.  It 
is  possible  that  these  cells  may  take  a  part  in  the  formation  of  new 
connective  tissue.  They  are  indistinguishable  from  the  immature 
form  of  connective  tissue-cells.  It  is  therefore  difficult  to  be  certain 
whether  the  wandering  and  the  fixed  connective-tissue  corpuscles  are 
of  identical  or  of  different  origin.  MetchnikofT  speaks  of  these  cells  as 
macrophages,  to  distinguish  them  from  the  pol}Tnorphonuclear  type, 
which  he  terms  micwphages. 

We  thus  see  that  several  types  of  the  wandering  cells  of  meso- 
blastic  origin  which  take  part  in  inflammation  do  not  exert  active 


THE  CELLULAR  MECHAXI8MS  OF  DEFENCE        1151 

phagoc}i:ic  properties  and  cannot  therefore  destroy  bacteria  or  other 
invading  organisms  by  the  process  of  ingestion  and  digestion.  Yet 
we  have  evidence  that  the  part  played  by  such  cells  in  the  defence  of 
the  organism  is  no  less  important  than  that  of  the  actively  phagocytic 
cells.  In  the  alimentation  of  the  more  primitive  invertebrata  the 
cells  lining  the  digestive  cavity  take  up  the  particles  of  food  directlv, 
and  the  processes  of  digestion  are  carried  out  in  vacuoles  within 
the  cells  themselves.  In  the  higher  animals  this  process  of  intra- 
cellular digestion  has  almost  disappeared,  and  the  cells  lining  the 
alimentary  tract  have  become  differentiated  into  those  which  secrete 
digestive  ferments  and  those  which  absorb  the  products  of  the  action 
of  the  ferments  on  the  food-stuffs.  Digestion  has  thus  become  extra- 
cellular. It  seems  that  a  similar  modification  has  taken  place  to 
some  extent  in  the  means  adopted  by  the  organism  for  its  defence 
from  infection,  and  that  the  leucocytes  destroy  bacteria  not  only  by  the 
process  of  intracellular  digestion  but  also  by  the  excretion  of  sub- 
stances into  the  surrounding  body  fluids  which  have  a  deleterious 
influence  on  bacteria.  Thus  normal  blood-serum  is  found  to  have  a 
strong  destructive  influence  on  most  species  of  bacteria,  whether 
pathogenic  or  not.  Since  this  property  is  not  shared  to  anything  like 
the  same  extent  by  the  blood-plasma,  it  may  be  ascribed  to  the  breaking 
down  of  leucocytes  in  the  process  of  clotting  and  the  consequent 
liberation  of  bactericidal  substances.  Extracts  made  from  anv 
collection  of  leucocytes  have  a  similar  bactericidal  effect,  and  it  has 
been  shown  by  Wright  that  the  ingestion  of  bacteria  by  normal  leuco- 
cytes goes  on  much  more  rapidly  in  the  presence  of  blood-serum  or 
,  if  the  bacteria  have  been  previously  subjected  to  the  action  of  blood- 
serum.  This  adj  uvant  action  of  blood-serum  on  phagocytes  is  destroyed 
if  the  serum  be  heated  to  55°  C,  so  that  it  must  be  due  to  the  presence 
of  some  chemical  substance  in  the  serum  which  is  unstable  and  destroyed 
by  heat  at  a  temperature  far  below  the  coagulation-point  of  the  senun 
proteins.  Moreover  there  are  many  species  of  pathogenic  bacteria 
which  cannot  infect  the  animal  as  a  whole.  These  nevertheless  mav 
multiply  on  the  surface  of  the  body  or  in  an  abscess  cavity  and  lead 
to  the  death  of  the  host,  in  consequence  of  the  production  by  the 
bacteria  of  soluble  toxins  which  are  absorbed  into  the  blood-stream. 
Examples  of  such  micro-organisms  are  those  which  are  associated  with 
tetanus  and  diphtheria.  The  process  of  intracellular  digestion  is 
obviously  inadequate  to  deal  with  such  cases,  and  since  we  have  the 
power  of  resisting  and  recovering  from  these  diseases  there  must  be 
other  mechanisms  at  the  disposal  of  the  body  for  the  neutralisation  of 
these  toxins.  The  protection  of  the  body  against  destruction  by 
bacterial  toxins  involves  in  fact  a  whole  series  of  chemical  mechanisms 
which  we  must  regard  as  of  equal  importance  and  as  co-operating  with 
the  phagocytic  mechanism. 


SECTION  II 

THE  CHEMICAL  MECHANISMS  OF  DEFENCE 

IMMUNITY.  All  infectious  diseases  are  caused  by  the  agency  of 
micro-organisms.  The  greater  number  of  these,  the  bacteria,  belong 
to  the  class  of  fungi  or  schizomycetes  ;  a  certain  number  must  be  classed 
with  the  yeasts,  while  others  are  protozoal  in  character.  It  is  especially 
in  the  first  class  of  diseases,  namely,  those  due  to  bacteria,  that^  the 
organism  has  developed  chemical  mechanisms  of  defence.  In^tfe  pro- 
tozoal diseases  the  micro-organisms  occur  for  the  greater  part  as  intra- 
cellular parasites.  One  attack  of  the  disease  does  not  as  a  rule  confer 
immunity,  and  the  treatment  has  to  be  sought  along  the  lines  of  medica- 
tion by  drugs  rather  than  by  the  development  of  methods  of  protection 
normally  displayed  or  developed  by  the  animal  which  is  the  subject  of 
the  infection.  The  diseases  due  to  bacteria  include  diphtheria,  tetanus, 
tubercle,  anthrax,  pyaemia,  and  many  others.  In  these  diseases  we 
have  to  deal  with  a  number  of  phenomena  more  or  less  common  to 
all.  The  infection  in  each  case  is  due  to  the  actual  transference  of 
the  specific  organism  from  one  animal  to  another.  After  the  micro- 
organism has  attained  entrance  into  the  system  there  is  a  period  of 
incubation  before  the  disease  actually  breaks  out.  When  this  occurs 
the  specific  microbe  is  to  be  found  in  large  quantities  either  in  the 
blood  or  in  the  tissues  of  the  body.  The  disease  is  generally  charac-  ^ 
terised  by  fever  and  often  by  local  lesions,  such  as  the  intestinal  ulcers 
of  typhoid,  or  the  glandular  swellings  of  bubonic  plague.  The  micro- 
organisms may  develop  in  the  animal  until  its  death,  or  the  disease 
may  terminate  in  recovery  and  the  total  disappearance  of  the  microbes 
from  the  body.  After  recovery  it  is  found  that  the  patient  is  protected 
from  reinfection  by  the  bacterium  which  was  the  cause  of  the  disease, 
and  this  condition  of  immunity  may  last  as  long  as  the  patient  lives. 
The  incidence  of  these  bacterial  diseases  is  not  the  same  for  all  animals, 
so  that  in  the  case  of  many  diseases  we  can  speak  of  a  natural  immunity 
of  certain  animals  for  the  diseases  in  question. 

The  pathogenic  micro-organisms  can,  in  a  number  of  cases,  be  culti- 
vated on  artificial  media  outside  the  body.  It  is  then  found  that 
they  may  be  divided  into  two  classes.  One  class,  of  which  the  diph- 
theria and  tetanus  bacilli  are  examples    secrete  into  the  surrounding 

culture  fluid  substances  which  act  as  virulent  poisons  when  injected 

1152 


THE  CHEMICAL  MECHANISMS  OF  DEFENCE        115:5 

into  animals.  Other  bacteria  do  not  form  such  extracellular  toxins, 
but  in  their  case  it  is  found  that  if  the  bodies  of  the  bacilli  be  broken  up 
the  injection  of  the  contents  of  the  bacteria  is  attended  with  poisonous 
effects.  The  bacteria  may  be  thus  classified  according  as  they  pro- 
duce extracellular  or  intracellular  toxins.  We  may  deal  first  with 
the  manner  in  which  the  body  reacts  to  the  toxins  excreted  bv  the 
first  class.  If  a  culture  of  diphtheria  or  tetanus  bacilli  he  filtered, 
the  clear  filtrate  free  from  bacilli  is  found  to  exercise  as  poisonous 
results  as  if  the  culture  itself  of  the  living  bacilli  had  been  employed. 
The  toxins  contained  in  these  fluids  are  extremely  potent.  Thus  five- 
•  millionths  of  a  gramme  of  tetanus  toxin  is  a  fatal  dose  for  a  mouse, 
and  -00023  grm.  would  kill  a  man.  These  weights  apply  to  the 
mixture  obtained  by  the  evaporation  of  the  solution  of  toxin,  so  that 
the  pure  toxin  must  be  even  more  powerful  than  ia  represented  in  these 
figures.  We  have  at  present  no  means  of  preparing  a  toxin  in  a  pure 
condition,  nor  do  we  know  to  what  class  of  compounds  it  should  be 
assigned.  The  toxin  is  an  unstable  body  and  is  destroyed  by  heating 
to  65°  C.  Similar  toxins  are  widely  distributed  throughout  the 
vegetable  and  animal  kingdoms.  Thus  they  form  the  active  con- 
stituent of  snake  venom  and  of  the  poison  of  scorpions  and  spiders. 
They  also  occur  in  the  seeds  of  castor  oil  and  of  jequirity,  the  toxins 
of  which  seem  to  be  of  protein  character  and  are  known  as  ricin  and 
abrin.  There  is  a  great  variability  in  the  reaction  of  different  animals 
to  these  toxins.  Thus  to  the  poison  of  tetanus  the  rabbit  is  two 
thousand  times  and  the  hen  twenty  thousand  times  more  resistant 
than  the  guinea-pig.  As  in  the  case  of  infection  by  bacteria  them- 
selves, a  certain  incubation  tin^e  is  necessary  after  the  introduction 
of  the  toxin  before  its  effects  are  displayed.  There  is  a  striking 
difference  in  this  respect  between  the  action  of  these  complex  bodies 
and  the  action  of  drugs,  such  as  strychnine  or  morphine.  Thus 
by  increasing  the  dose  of  strychnine  it  is  possible  to  kill  an  animal 
within  half  a  minute.  The  period  of  survival  after  the  injection  of  a 
dose  of  toxin  cannot  be  reduced  beyond  a  certain  limit,  however  much 
toxin  be  injected.  Thus  a  lethal  dose  of  diphtheria  toxin  kills  a  guinea- 
pig  in  fifteen  hours.  If  ninety  thousand  such  doses  be  injected  into  a 
guinea-pig  it  is  not  possible  to  reduce  the  time  of  survival  below 
twelve  hours.  Another  characteristic  of  these  toxins  is  the  specificity 
of  their  action.  One  kind  of  toxin  may  act  chiefly  on  the  central 
nervous  system,  another  on  the  peripheral  nerves,  another  on  the  red 
blood-corpuscles.  In  this  respect  of  course  they  resemble  ordinary 
drugs.  Associated  with,  however,  and  apparently  a  necessary  con- 
dition of,  this  specific  action  is  the  actual  combination  which  occurs 
between  the  toxin  and  the  organ  on  which  it  exerts  its  effect.  Thus 
tetanus  toxin  has  a  specific  affinity  for  the  central  nervous  system, 

73 


1154  PHYSIOLOGY 

and  may  be  removed  from  a  solution  by  shaking  the  latter  up  with 
an  emulsion  of  brain.  In  spite  of  the  excessively  fatal  character  of 
these  toxins  it  is  possible  to  render  an  animal  immune  to  their  action. 
If  a  dose  of  diphtheria  or  tetanus  toxin  which  is  smaller  than  the  fatal 
dose  be  injected  into  an  animal,  the  latter  may  show  signs  of  injur}^ 
from  which  it  recovers.  When  recovery  is  complete  it  is  found  that 
three  or  four  times  the  fatal  dose  may  be  injected  without  producing 
any  e\al  effects,  and  this  process  of  injection  of  toxin  may  be  repeated 
in  continually  increasing  doses  until  the  animal  is  able  to  withstand 
a  dose  one  hundred  thousand  times  as  large  as  that  which  would  have 
been  fatal  to  it  in  the  first  instance.  When  a  condition  of  immunity 
has  been  produced  in  this  way  it  is  found  that  the  blood-serum  of  the 
animal  has  the  power  of  neutralising  the  toxin.  Thus  if  the  blood- 
serum  from  a  horse  which  has  been  treated  "with  large  doses  of  diph- 
theria toxin  be  mixed  with  an  equal  quantity  of  the  toxin  itself,  the 
mixture  may  be  injected  into  susceptible  animals  without  the  produc- 
tion of  any  effect.  It  is  possible  in  this  way  to  get  a  serimi  1  c.c.  of 
which  will  neutralise  many  fatal  doses  of  the  toxin,  and  the  antitoxic 
serum  may  be  injected  into  a  susceptible  animal  and  used  to  confer 
an  artificial  immunity  on  the  latter,  or  may  be  injected  into  a  diseased 
animal  and  used  thus  as  a  curative  agent.  Antitoxin  thus  plays  a 
great  part  in  modern  therapeutics,  especially  of  diphtheria.  In  the 
case  of  tetanus  the  toxin  has  a  specific  affinity  for  the  nervous  system 
and  apparently  travels  up  the  axis  cylinders  of  the  nerves  to  the  central 
nervous  system.  By  the  time  that  it  has  arrived  at  the  central 
nervous  system,  and  the  spasms  typical  of  tetanus  have  broken 
out,  the  toxin  is  already  so  firmly  bound  to  the  reacting  tissue  that 
the  injection  of  antitoxin  into  the  blood-stream  has  Uttle  or  no 
eSect  on  the  course  of  the  disorder.  The  use  of  the  tetanus  antitoxin  is 
therefore  chiefly  as  a  prophylactic  agent. 

The  question  of  the  manner  in  which  the  antitoxin  is  able  to  com- 
bine with  and  neutralise  the  toxin  is  one  of  considerable  practical 
importance.  In  this  process  we  have  relations  presenting  marked 
analogies  with  the  neutralisation  of  acids  by  bases.  If  we  define  a 
unit  of  toxin  as  that  amount  which  possesses  a  certain  power,  i.e. 
which  will  kill  a  guinea-pig  in  so  many  days,  or  \a\\  cause  the  complete 
haemolysis  of  1  c.c.  of  blood  in  two  and  a  haK  hours,  we  can  find  the 
amount  of  anti-body  which  is  just  sufficient  to  neutralise  this  effect, 
and  this  amount  of  anti-body  can  be  regarded  also  as  one  unit.  If 
instead  of  one  unit  of  each  we  take  100  units,  the  neutralisation  is 
effected  in  the  same  way.  The  process  is  found,  however,  to  be  more 
complex  when  we  take  100  units  of  toxin  or  lysin  and  attempt  to  neu- 
tralise them  by  the  fractional  addition  of  antitoxin.  In  the  case 
of  a  strong  acid  and  strong  alkali  we  know  that  if  100  c.c.  of  alkali 


THE  CHEMICAL  MECHANISMS  OF  DEFENCE        1155 

are  just  sufficient  to  neutralise  100  c.c.  of  acid,  the  addition  of  50  c.c. 
of  alkali  will  leave  half  the  acid  unneutralised.  If,  however,  we  try 
the  same  experiment  in  the  case  of  mixtures  of  toxin  and  antitoxin,  it 
will  be  found  that  the  addition  of  50  c.c.  of  antitoxin  will  neutralise 
much  more  than  half  of  the  toxin,  and  the  same  applies  to  other  bodies 
of  this  class.  Ehrlich  has  attempted  to  explain  this  result  by  assuming 
that  in  any  toxin  there  is  a  mixture  of  substances,  some  having  a  | 
strong  affinity  for  the  antitoxin,  and  others,  which  he  calls  toxones, 
possessing  only  a  slight  affinity.  In  the  50  c.c.  of  toxin  first  added 
the  toxins  would  satisfy  all  their  combining  powers,  whereas  the  toxones 
would  not  begin  to  combine  until  they  were  present  in  large  excess. 
Arrhenius  and  Madsen  have  drawn  an  analogy  between  the  neutralisa- 
tion of  toxin  by  antitoxin  and  the  neutralisation  of  a  weak  acid,  such 
as  boracic  acid,  by  a  weak  base,  such  as  ammonia.  They  show  that  in 
this  case  the  general  course  of  events  would  be  similar  to  that  observed 
by  Ehrlich.  At  no  time  would  there  be  complete  neutralisation,  owing 
to  the  fact  that  hydrolysis  constantly  occurs,  so  that  when  equivalent 
quantities  of  each  substance  had  been  added,  the  fluid  would  still 
contain  a  certain  amount  of  free  base  alongside  of  free  acid,  in  addition 
to  the  salt  produced  by  the  combination  of  the  two.  It  is  impossible, 
however,  to  account  for  all  the  phenomena  presented  in  the  neutralisa  • 
tion  of  toxin  by  antitoxin  in  this  simple  manner.  Thus  seventeen 
parts  of  ammonia  would  neutralise  exactly  an  equivalent  quantity  of 
boracic  acid,  whether  these  substances  were  dissolved  in  10  c.c.  or 
in  100  c.c.  of  water.  If,  however,  it  be  found  that  1  c.c.  of  antilysin 
exactly  neutralises  1  c.c.  of  lysin,  these  two  substances  will  no  longer 
be  in  equilibrium  when  the  whole  is  diluted  up  to  10  c.c.  with  water. 
If  a  neutral  mixture  of  lysin  and  antilysin  be  taken  and  filtered  under 
pressure  through  a  gelatin  filter,  no  lysin  or  antilysin  passes  through 
the  filter,  so  that  the  residue  on  the  filter  becomes  concentrated.  On 
examining  this  residue  it  is  found  that  it  has  a  strong  haemolytic  action, 
and  the  vSame  is  true  of  the  substance  which  may  be  obtained  by 
melting  the  gelatin  out  of  the  pores  of  the  filter.  It  is  evident  that, 
even  in  a  neutralised  mixture,  both  free  lysin  and  free  antilysin,  or 
free  toxin  and  free  antitoxin,  are  present,  and  it  needs  only  the  altera- 
tion of  the  physical  condition  of  the  mixture  in  order  to  display  the 
action  of  one  or  other  of  these  bodies.  How  then  are  we  to  regard  this 
combination  of  toxin  with  antitoxin  ?  Craw  has  pointed  out  that 
the  combination  is  in  alL  respects  comparable  to  that  which  occurs 
between  adsorbing  surfaces  and  many  dyestufEs.  If  we  place  some 
filter  paper  in  a  solution  of  fuchsin  or  Congo  red,  the  filter  paper  will 
take  up  the  dye  substance.  The  amount  taken  up  by  the  paper  will 
increase  with  increase  in  concentration  of  the  solution.  There  will, 
however,  be  a  tendency  to  the  formation  of  false  equilibrium  points. 


1156  PHYSIOLOGY 

as  in  the  case  of  the  reaction  of  toxin  and  antitoxin.  Thus  if  two 
sohitions  of  fiichsin  be  made  and  to  each  a  sheet  of  filter  be  added, 
but  in  one  case  the  paper  be  added  at  once,  and  in  the  other  case  in  three 
parts  at  intervals  of  twelve  hours,  at  the  end  of  thirty-six  hours  the  paper 
which  has  been  added  in  parts  will  have  removed  more  dyestuff  from 
the  solution  than  is  the  case  where  the  whole  amount  of  paper  was 
added  at  once.  In  the  same  way,  when  treating  a  suspension  of 
bacilli  with  an  aggiutinatjug  Si?jum^  it  is  found  that  the  successive 
addition  of  the  bacillary  suspension  to  the  serum  removes  more 
agglutinin  from  the  solution  than  when  the  addition  is  made  at  one 
time. 

The  interactions  therefore  between  these  bodies  must  be  looked 
upon  as  special  examples  of  the  group  of  phenomena  known  as  adsorp- 
tion, such  as  the  adsorption  of  iodine  from  solutions  by  charcoal,  of 
iodine  from  water  by  starch,  or  of  ammonia  by  charcoal.  The  exact 
adsorption  which  takes  place  must  be  a  function  of  the  chemical  con- 
figuration of  the  substance  forming  the  surface,  since  otherAnse  it 
would  be  impossible  to  account  for  the  extremely  specific  character 
of  the  interaction  between  toxins  and  their  corresponding  anti- 
toxins. The  interaction  must  therefore  be  assigned  to  that  special 
class,  in  which  we  have  already  placed  the  action  of  ferments,  which 
is  not  entirely  chemical  nor  entirely  physical,  but  depends  for  its 
existence  on  a  co-operation  of  both  chemical  and  physical  factors. 

How  are  we  to  account  for  the  production  of  the  antitoxin  as  a 
result  of  the  injection  of  toxins  into  the  body,  a  production  which  is 
proportional  to,  but  far  transcending  in  amount,  the  toxin  injected  ? 
In  all  the  speculations  on  the  mode  of  production  and  action  of  anti- 
toxins an  imj)ortant  part  has  been  played  by  a  conception  put  forward 
by  Ehrlich  in  1885  of  the  nature  of  the  living  protoplasmic  molecule. 
According  to  this  conception,  which  is  spoken  of  as  the  '  side-chain 
theory,'  each  unit  of  hving  matter  consists_of_a  centrally  placed 
protein  gi'oup  with  a  number  of  side-chains  attached  to  it,  on  the 
analogy  of  the  hypothetical  configuration  of  the  benzene  ring,  to  each 
corner  of  which  may  be  attached  an  aliphatic  chain.  To  explain  the 
phenomena  of  nutrition  and  oxidation  Ehrlich  regarded  some  of  these 
side-chains  as  corresponding  to  unoxidised  food  substances,  while 
others  of  the  side-chains  had  a  strong  afl&nity  for  oxygen  and  might  be 
regarded,  when  fully  saturated  with  this  substance,  as  peroxide  in 
character.  Activity  in  such  a  unit  would  be  associated  with  inter- 
action between  these  two  sets  of  side-chains.  As  a  result  the  food 
chain  would  be  converted  to  carbon  dioxide  and  an  affinity  left 
unsaturated  until  it  could  take  up  another  food-molecule.  In  the  same 
way  the  oxygen  side-chain,  having  lost  the  greater  part  of  its  oxygen, 
would  have  a  strong  affinity  for  this  element  and  would  re-saturate 


THE  CHEMICAL  MECHANISMS  OF  DEFENCE        1157 

itself  at  the  expense  of  the  oxygen  brought  to  it  by  the  blood.  Ehrlich 
regards  the  toxins  as  partaking  essentially  of  the  same  character  as  the 
protoplasmic  molecule,  as  being  in  fact  protoplasmic  fragments 
differing  only  from  the  protoplasm  of  the  cell  in  the  greater  simplicity 
of  arrangement  of  their  side-chains.  According  to  him  the  central 
group,  or  nucleus,  of  the  toxin  possesses  two  side-chains,  one  of  which 
by  its  stereomeric  configuration  is  peculiarly  adapted  to  fit  on  to  the 
organ  or  cell  of  the  body  which  the  toxin  or  active  body  attacks,  and 
is  known  as  the  haptophore  group,  and  another  side-chain,  the  toxo- 
pJiore  group,  which  is  responsible,  wJien  t£e  toxin  is  once  anchored, 
for  the  destructive  changes  ^^'rought  by..th.e  toxin  on  the  cell  of  the  , 
body.  The  antitoxins  or  antilysins  are  thus  supposed  to  act  in 
virtue  of  their  adaptation  to  the  haptophore  gi"0up,  so  as  to  combine 
with  the  toxin  or  lysin  and  prevent  these  from  exercising  their 
injurious  effects  on  the  body.  Ehrlich  has  shown  that  in  many  toxins 
the  toxophore  can  undergo  weakening  or  destruction  Avithout  any 
alteration  of  the  haptophore  group  ;  such  modifications  he  designates 
as  '  toxoids.'  They  have  the  same  combining  power  for  antitoxins 
as  is  possessed  by  the  ordinary  toxins,  but  are  either  without  physio- 
logical effect,  or  their  poisonous  characters  are  only  a  fraction  of  that 
possessed  by  ordinary  toxin. 

The  formation  of  antitoxins  is  accounted  for  (or  rather  described) 
on  this  hypothesis  in  the  following  mamier.  When  a  receptor  side- 
chain  of  the  cell  is  occupied  by  becoming  attached  to  the  haptophore 
group  of  the  toxin,  this  side-chain  is,  so  to  speak,  shut  out  from  the 
normal  activities  of  the  cell.  A  defect  is  thus  produced  in  the  cell 
which  the  latter  endeavours  to  adapt  itself  to  by  the  production  of 
other  side-chains  of  the  same  character.  It  may  be  regarded  as  a 
general  rule  in  living  tissues  that  a  reaction  tends  to  be  an  over- 
reaction,  so  that  the  compensation  by  the  cell  should  more  than  make 
good  the  defect  produced  by  the  attachment  of  the  toxin.  We  thus 
get,  not  one,  but  a  number  of  side-chains  produced  of  the  same  character 
as  that  occupied  by  the  toxin  molecule,  and  therefore  able  also  to  act 
as  receptors  for  the  haptophore  group  of  the  toxin.  These  new  receptor 
side-chains,  being  produced  in  excess,  are  supposed  by  Ehrlich  to  be 
thrown  off  from  the  cell  and  to  circulate  in  the  body-fluids  (Fig.  484,  4). 
A  nunil)er  of  prcjtoplasmic  fragments  are  thus  set  free  wliich  have  a 
specific  power  of  uniting  with  the  toxin,  and  it  is  this  excess  of  side- 
chains  thrown  off  from  the  coll  which  represents  the  antitoxin  molecules 
found  circulating  in  the  blood  after  the  injection  of  toxins.  It  will 
be  noted  that  this  theory,  though  chemical  in  form,  is  really  purely 
biological.  It  does  not  explain  the  phenomena  by  reference  to  the 
kn6wn  laws  of  chemistry,  but  is  a  manner  of  viewing  the  biological 
phenomena  which  facilitates  their  description  and  discussion  and 


1158 


PHYSIOLOGY 


enables  us  to  classify  the  very  complex  phenomena  of  immunity  in  a 
more  or  less  imperfect  fashion. 

The  property  of  giving  rise  to  anti-bodies  on  injection  into  an  animal 
is  not  confined  to  toxins,  a  large  number  of  substances,  e.g.  egg  albumin, 
serum,  proteins,  ferments,  albumoses,  partaking  of  the  same  property. 
All  such  substances  are  classed  together  as  antigens.  Thus  human 
serum  injected  into  a  rabbit  produces  in  the  rabbit's  serum  some 
body  which  will  give  a  precipitate  when  mixed  with  human  serum 


Fig.  484.  Schematic  representation  of  formation  of  antitoxin  as  side-chains  of 
protoplasmic  molecule.  The  black  bodies  are  the  toxin  molecules  which  fit 
by  their  haptophore  end  on  to  the  side-chains  of  the  cell.     (Ehklich.) 


even  in  minute  traces.  This  precipitin  forraation  is  specific,  so  that 
it  may  be.  used  as  a  test  1ofHie~origin  of  any  unknown  specimen  of 
serum.  In  the  same  way  rennet  fejnient  when  injected  gives  rise  to  the 
production  of  an  anti-rennin  which  will  neutralise  the  action  of  this 
ferment  on  milk.  Antigens  are  all  colloidal  in  character  and  probably 
optical  y  active.  Ordinary  drugs  do  not  give  rise  to  the  formation  of 
anti-bodies,  a  necessary  condition  being  apparently  some  similarity  in 
the  molecular  structure  of  the  antigen  to  the  protoplasm  of  the  animal 


THE  CHEMICAL  MECHANISMS  OF  DEFENCE        1159 

on  which  it  acts  and  to  which  it  becomes  linked  by  its  haptophore 
group. 

CYTOLYSINS.  The  bacteria  of  tetanus  and  diphtheria  cannot 
exist  in  the  body,  infection  by  thena  being  limited  to  a  surface  or  abscess 
cavity.  When  a  disease  involves  infection  of  the  tissues  themselves  by 
living  micro-organisms,  somewhat  more  complicated  mechanisms  are 
brought  into  play  for  the  defence  of  the  organism.  We  have  already 
seen  that  normal  blood-serum  may  exert  a  paralytic  or  destructive 
action  on  bacteria.  Light  has  been  thrown  on  the  factors  involved  in 
this  destruction  by  a  study  of  the  phenomenon  of  hcemolysis,  i.e.  the 
destruction  of  red  blood-corpuscles.  Normal  goat's  serum  may  be  mixed 
with  the  red  blood-corpuscles  of  the  sheep  without  any  injury  to  the 
latter.  If,  however,  sheep's  corpuscles,  previously  washed  in  normal 
saline,  be  injected  at  intervals  of  a  few  days  into  a  goat,  the  goat's  serum 
is  found  to  have  acquired  the  power  of  rapidly  dissolving  the  red  blood- 
corpuscles.  This  hsemolytic  power  is  obvious,  since  it  is  only  necessary 
to  mix  the  serum  and  the  washed  blood-corpuscles  together  and  allow 
the  mixture  to  stand  in  a  narrow  tube.  The  corpuscles  rapidly  sink  to 
the  bottom,  leaving  the  colourless  serum  above,  unless  haemolysis  has 
occurred,  in  which  case  the  serum  will  be  of  a  transparent  red  colour. 
If  the  ha)molytic  serum  be  heated  to  55°  C.  it  is  found  to  have  lost  its 
power  of  dissolving  sheep's  corpuscles.  This  power  is  at  once  restored 
if  to  the  heated  serum  be  added  any  normal  blood-serum,  even  of  the 
sheep  itself.  It  seems  therefore  that  two  substances  are  involved 
in  the  haemolysis,  namely,  (a)  a  substance  present  in  most  normal 
sera  which  is  destroyed  at  a  temperature  of  60°  C.  and  has  been  called 
the  comflement,  and  (6)  a  substance  present  in  the  serum  only  as  a 
result  of  the  previous  injection  of  some  species  of  red  blood-corpuscle, 
which  is  resistant  to  the  action  of  heat,  and  is  called  the  amhoceptor. 
The  reason  for  these  names  will  be  at  once  apparent  from  the  following 
experiment.  Heemolytic  goat's  serum  is  mixed  with  sheep's  red  blood- 
corpuscles  and  the  whole  mixture  kept  at  0°  C,  at  which  temperature 
haemolysis  is  indefinitely  delayed.  After  some  time  the  corpuscles 
are  separated  by  means  of  the  centrifuge.  On  testing  the  supernatant 
fluid  it  is  found  to  have  no  action  on  sheep's  corpuscles,  though  it  still 
possesses  the  power  of  activating  another  specimen  of  serum  which 
has  been  heated.  The  serum  separated  from  the  corpuscles  has  thus 
lost  the  amboceptor,  but  retained  the  complement.  The  amboceptor 
is  found  to  have  attached  itself  to  the  red  blood-corpuscles.  If  these 
be  washed  and  then  added  to  normal  sheep's  serum,  i.e.  serum  con- 
taining the  complement,  they  are  rapidly  dissolved.  When  solution 
has  taken  place  both  complement  and  amboceptor  are  found  to  have 
disappeared.  The  function  of  the  amboceptox  thus  seems  to  be  to 
enable  the  complement  already  present  in  normal  serum  to  act  upon 


1160  PHYSIOLOGY 

the  red  blood-corpuscles.  We  may  regard  the  amboceptor  therefore 
as  having  two  haptophore  grovips,  one  of  which  anchors  on  to  the  red 
blood-corpuscle,  while  the  other  attaches  itself  to  the  complement  (Fig. 
485,  7).  The  amboceptor  plus  the  complement  thus  comes  to  resemble 
the  toxin  molecule,  having  a  free  haptophore  group  at  one  end  and  a 
toxophore  group  (the  complement)  at  the  other  end.  The  reaction 
to  the  injection  of  the  red  blood-corpuscles  consists  in  the  formation 
of  the  amboceptor,  which  is  essentially  the  anti-body  of  the  red  blood- 
corpuscle  (Fig.  485,  8).  Similar  specific  anti-bodies  effecting  the 
dissolution  of  cells  or  organisms  maybe  produced  by  the  injection  of 
various  species  of  bacterium  or  of  animal  cells,  such  as  leucocytes,  sper- 
matozoa, liver-cells,  &c.,  and  there  can  be  no  doubt  that  bacteriolytic 
substances  play  a  considerable  par^  in  acquired  immunity. 


Fig.  485.     Diagram  to  show  the  rtlation  of  amboceptor  ami  complement 
to  the  animal  cell  (7)  and  to  red  coriniscles  (8).     (Ehrlich.) 

OPSONINS.  In  some  cases  the  anti-bodies  produced  by  the 
injection  of  living  or  dead  micro-organisms  do  not  bring  about  actual 
destruction  of  the  bacteria,  but  alter  them  in  such  a  way  as  to  make 
them  more  susceptible  to  the  action  of  the  phagocytes.  If  washed 
white  blood-corpuscles  be  mixed  with  micrococci,  such  as  those  found 
in  an  ordinary  boil,  they  are  found  to  take  up  the  micro-organisms  in 
considerable  numbers.  The  numbers  taken  up  are  much  increased  in 
the  presence  of  serum  derived  from  an  individual  who  has  received 
repeated  minute  injections  of  the  dead  micrococci  in  question.  To  the 
substance  in  the  serum  whicli  thus  prepares  the  micrococci  for  ingestion 
by  the  phagocytes  Wright  has  given  the  name  of  ojj.snniu.s.  The 
opsonic  index  of  the  leucocytes  of  any  individual  m  reference  to 
a  given  species  of  microbe  is  determined  by  observing  the  number  of 
the  microbes  taken  up  by  the  leucocytes  after  treatment  with  the 
serum  of  the  individual  and  comparing  it  with  the  number  taken 


THE  CHEMICAL  MECHANISMS  OF  DEFENCE         IHW 

up  by  the  same  leucocytes  when  the  bacteria  have  been  treated  with 
the  serum  of  an  average  individual. 

We  thus  see  that  immunity,  whether  innate  or  acquired,  is 
extremely  complex  in  character  and  may  depend  on  one  or  more  of 
many  factors.  The  immunity  of  an  animal  to  any  given  infection 
may  be  determined  by  the  absence  of  haptophore  groups  in  his  body 
for  the  toxin  excreted  by  the  microbe  responsible  for  the  infection, 
or  by  the  fact  that  the  haptophore  groups  are  present  but  are  con- 
fined to  tissues  on  which  the  toxophore  group  can  have  no  iriflueiice. 
Thus,  e.g.,  an  attachment  of  the  tetanus  toxin  to  a^connective-tissue 
cell  would  bo  without  effect  on  the  health  of  the  body.  Again, 
immunity  may  be  due  to  the  efficacy  of  the  phagocytes,  either  of  the 
ftef(Js  or  the  connective  tissues,  iiTirigesting  and  destroying  the  micro- 
organism, and  this,  as  we  have  seen,  may  again  be  dependent  on  the 
])resence  or  absence  in  the  body-fluids  of  substances  which,  while  not 
destroying  the  micro-organisms,  render  them  more  accessible  to  the 
action  of  the  phagocytes.  In  those  cases  where  the  infecting  organism 
secretes  a  specific  toxin,  the  main  line  of  defence  and  the  main  factor 
in  the  production  of  immunity  is  the  formation  of  specific  antitoxins 
to  the  poison  in  question.  FiioaJly  there  may  be  produced  as-a-*esult 
of  the  excess  of  micro-organisms  substances  such  as  the  amboceptprs, 
which  render  the  micro-organisms  susceptible  to  destruction  by  the 
complements  or  cytases  normally  present  in  the  circulating  fluids  and 
possibly  themselves  derived  from  the  activity  or  destruction  of  the 
leucocytes  and  other  phagocytes  of  the  body. 

In  this  short  description  we  have  only  been  able  to  touch  upon  the 
most  salient  features  of  the  immunity  problem.  The  question  enters 
strictly  into  physiology  since,  as  we  have  seen,  it  involves  adaptations 
on  the  part  of  the  organism  to  changes  in  itself  or  its  environment. 
For  the  practical  application  of  these  facts,  as  well  as  the  consideration 
of  the  minuter  details  and  exceptions,  we  must  refer  the  student  to 
works  especially  dealing  with  the  subjects  of  infectious  diseases  and 
immunity. 


CHAPTER  XVI 
RESPIRATION 

SECTION  I 

THE  MECHANICS  OF  THE  RESPIRATORY 
MOVEMENTS 

In  unicellular  animals  the  interchange  of  gases,  i.e.  the  intake  of 
oxygen  and  the  output  of  carbon  dioxide,  is  as  a  rule  carried  out  by 
processes  of  diffusion  occurring  at  the  surface  of  the  cell.  With 
increased  size  of  the  organism  the  surface  becomes  insufficient  for  this 
purpose,  and  special  organs  make  their  appearance  for  presenting  a 
large  extent  of  surface  to  the  surrounding  medium.  In  the  multi- 
cellular animals  the  actual  process  of  tissue  respiration  is  carried  out 
between  the  internal  medium,  lymph,  blood,  &c.,  and  the  individual 
cells,  and  the  use  of  the  special  organ  of  respiration  is  to  bring  the 
circulating  internal  medium  in  intimate  relation  over  a  large  area 
with  the  surrounding  fluid,  whether  air  or  water.  In  insects  we 
find  a  large  branched  system  of  tubes,  the  tracheae,  which  contain 
air  and  are  distributed  to  the  finest  tissues,  renewal  of  the  air  in  the 
tubes  being  provided  for  by  special  respiratory  movements.  In 
most  water  animals  the  respiratory  organ  is  known  as  the  gills,  and 
presents  a  large  surface  well  supplied  with  circulating  blood  over 
which  a  continual  stream  of  the  surrounding  water  is  kept  up.  In 
all  these  animals  therefore  we  can  distinguish  two  processes,  viz. 
(1)  the  interchange  of  gases  between  the  tissue-cells  and  the  surrounding 
lymph,  '  internal  respiration  '  ;  (2)  the  interchange  of  gases  between 
the  circulating  fluid  and  the  external  medium,  '  external  respiration.' 
In  all  land-breathing  vertebrates  the  organs  of  external  respiration, 
the  lungs,  arise  as  paired  diverticula  of  the  anterior  part  of  the  ali- 
mentary canal.  The  renewal  of  the  air  in  the  air-sacs  formed  from 
these  diverticula  is  effected  by  alternate  increase  and  diminution  in 
their  size  caused  by  the  movements  of  respiration,  while  a  rapid  circu- 
lation of  blood  is  carried  out  through  a  fine  meshwork  of  capillaries 
just  underneath  the  surface  of  the  sacs.  In  man  the  organs  of  external 
respiration,  the  lungs,  are  built  up  in  the  following  way  : 

The  trachea  or  windpipe,  a  wide  tube  about  4^  inches  long,  divides 

1162 


MECHANICS  OF  RESPIRATORY  MOVEMENTS       1163 

below  into  two  main  branches — bronchi  ;  and  these  subdivide  again 
and  again,  becoming  gradually  smaller.  The  terminal  ramifications 
or  bronchioles  open  into  rather  wider  parts — the  infundibula,  the  walls 
of  which  are  beset  with  a  number  of  minute  cavities,  the  alveoli.  The 
larger  tubes  are  kept  patent  by  rings  or  plates  of  cartilage  in  their 
walls.  The  smaller  tubes  have  no  cartilage,  their  walls  being  com- 
posed of  fibrous  and  elastic  tissue  and  a  coating  of  unstriated  mus- 
cular fibres,  which  are  able  by  their  contraction  to  occlude  the  passage. 
The  whole  system  of  tubes  is  hned  with  a  layer  of  epithelium — 
ciliated  columnar  in  the  trachea,  bronchi,  and  bronchioles,  and 
cubical  over  the  parts  of  the  infundibulum  not  occupied  by  air- 
cells.  The  alveoli  are  the  special  respiratory  parts  of  the  lung.  Their 
walls  are  composed  of  connective  tissue  con- 
taining a  large  number  of  elastic  fibres,  and 
are  covered  internally  by  a  single  layer  of 
extremely  thin  large  flattened  cells.  The 
alveoli  are  closely  packed  together,  so  that 
in  a  section  of  the  lung  an  alveolus  is  seen 
to  be  in  contact  with  others  on  all  sides. 
Immediately  below  the  squamous  epithelium 
ramify  blood-capillaries  derived  from  the 
pulmonary  artery.  These  form  a  close  net- 
work, and  the  blood  in  them  is  in  proximity 
to  air  on  two  sides,  being  separated  from  the 
air  in  the  alveoli  only  by  the  thin  endothelial 
cells  of  the  capillary  wall  and  the  flattened 
cells  lining  the  alveoli. 

The  lungs  in  their  development  grow  out  "^'"^ese'u.Sn  °o?X "LT 
from  the  fore  part  of  the  alimentary  canal  ture  of  the  lungs.  The 
•    ,       ,1       f        ,  -       p   .  T_      1      1  -J.  trachea  branches  into  two 

mto  the  front  part  of  the  body-cavity  on      bronchi,  which    subdivide 

each  side — the      pleural      cavity.      The    SUr-        again  and  again  before  end- 
T       1      T  ,,    1  ,  ,1  T  T_  ing    in     the     infundibula. 

roundnig  body- walls  become  strengthened  by      (jvom  Yeo.) 

the  formation  of  the  ribs,  so  that  the  lungs 

are  suspended  in  a  bony  cage-work,  the  thorax.  Their  outer  surface  is 
covered  with  a  special  membrane,  the  pleura,  which  is  reflected  on  to 
the  wall  of  the  thorax  from  the  roots  of  the  lungs,  and  completely 
lines  the  cavity  in  which  they  lie.  The  surface  of  the  pleura  facing 
the  pleural  cavity  is  lined  \vith  a  continuous  layer  of  flattened  endo- 
thelial cells,  and  is  kept  moist  by  the  secretion  of  lymph  into  the 
cavity.  Thus,  being  attached  to  the  thorax  only  where  the  bronchi 
and  gieat  vessels  enter,  the  lungs  are  able  to  gUde  easily  over  the  inner 
surface  of  the  thorax,  with  which  under  normal  circumstances  they 
are  in  intimate  contact. 

A  constant  renewal  of  the  air  in  the  lungs  is  secured  by  move- 


1164  PHYSIOLOGY 

nieiits  of  the  thorax,  which  constitute  normal  breathing.  With 
inspiration  the  cavity  of  the  thorax  is  enlarged,  and  the  lungs  swell  up  to 
fill  the  increased  space.  The  capacity  of  the  air-passages  of  the  lungs 
being  thus  increased,  air  is  sucked  in  through  the  trachea.  The  move- 
ment ot  iuopiration  is  followed  by  that  of  expiration,  which  causes 
diminution  of  the  capacity  of  the  thorax  and  expulsion  of  air.  At  the 
end  of  expiration  there  is  normally  a  slight  pause.  The  number  of  respi- 
rations in  the  adult  is  about  17  or  18  a  minute.  This  is,  however,  much 
influenced  by  various  conditions  of  the  body,  and  also  by  the  age  of  the 
individual.  Thus  a  new-born  child  breathes  about  44  times  a  minute, 
a  child  of  five  about  26  times,  a  man  of  tw^enty-five  about  16,  and  of 
fifty  about  18.  The  frequency  is  increased  by  any  muscular  effort, 
so  that  even  standing  up  increases  the  number  of  respirations.  These 
movements  are  much  affected  by  psychical  activity  ;  they  are  to.  a 
certain  extent  under  the  control  of  the  will,  although  they  can  occur 
in  an  animal  deprived  of  its  brain,  and  are  normally  carried  out  without 
any  special  act  of  volition.  We  can  breathe  fast  or  slow  at  pleasure, 
and  can  even  cease  breathing  for  a  time.  It  is  impossible,  however,  to 
prolong  this  respiratory  standstill  for  more  than  a  minute  ;  the  need 
of  breathing  becomes  imperative,  and  against  oar  will  we  are  forced  to 
breathe. 

With  every  inspiration  the  cavity  of  the  thorax  is  enlarged  in  all 
dimensions,  from  above  downwards  by  the  contraction  of  the  dia- 
phragm, and  in  its  transverse  diameters  by  the  movements  of  the  ribs.* 

The  diaphragm  is  a  sheet  separating  the  cavity  of  the  chest  from 
that  of  the  abdomen.  It  consists  of  a  central  tendon  which  forms  an 
arched  double  cupola,  to  the  circumference  of  which  are  attached 
muscle-fibres.  The  diaphragmatic  muscles  present  two  main  divisions, 
namely,  (1 )  the  spinal  or  crural  part,  the  fibres  of  which  arise  from  the 
upper  three  or  four  lumbar  vertebrae  and  from  the  arcuate  ligaments 
and  are  inserted  into  the  posterior  margin  of  the  central  tendon  ;  and 
(2)  the  sterno-costal  part,  which  arises  by  a  series  of  digitations  from 
the  cartilages  and  adjoining  bony  parts  of  the  lower  six  ribs  and 
from  the  back  of  the  ensiform  process.  These  latter  fibres  pass  back- 
wards as  they  ascend.  In  the  cavity  of  the  larger  dome  on  the  right 
side  lies  the  liver,  while  the  smaller  dome  on  the  left  side  is  occupied 
by  the  spleen  and  stomach.  These  viscera  in  the  normal  condition 
are  pressed  against  the  under-surface  of  the  diaphragm  by  the  elas- 
ticity of  the  abdominal  walls.  The  central  part  of  the  diaphragm 
is  thus  pressed  up  into  the  chest,  partly  by  the  intra-abdominal 
pressure  and  partly  by  the  elastic  traction  of  the  distended  lungs. 

*  The  .student  is  advised  to  consult  the  article  by  Keith  on  tlu>  '  Mechanism 
of  Respiration  in  Man  '  for  a  fuller  account  of  this  subject  (L.  Hill's  '  Further 
Advances  in  Physiology,'  1909). 


MECHANICS  OF  RESPIRATORY  MOVEMENTS        1105 


The  upper  surface  of  the  central  tendon  is  united  to  the  pericardium^ 
This  part,  during  expiration,  is  the  deepest  part  of  the  middle  portion 
of  the  diaphragm.  Towards  the  back  of  the  pericardial  attachment 
the  central  tendon  is  pierced  for  the  passage  of  the  inferior  vena  cava. 
In  expiration  the  lateral  muscular  zone  of  the  diaphragm'lies  in  con- 
tact with  the  lower  part  of  the  thoracic  wall.  During  inspiration  the 
muscle  fibres  contract  and  draw  the  central  tendon  downwards,  so 
that  the  lower  surface  of  the  lungs  descends.  The  enlargement  of  the 
lungs  at  the  lower  part  of  the  thorax  is  aided  by  the  abduction  of  the 
floating  ribs,  produced  by  the  contraction  of  the  qiuidratus  lumborum 
and  deep  costal  muscles.  In  this  contraction  the  diaphragm  presses 
on  the  contents  of  the  abdomen,  so  that  the 
abdomen  swells  up  with  each  inspiratory  move- 
ment. The  middle  of  the  central  tendon,  where 
the  heart  lies,  moves  less  than  the  two  domes, 
and  the  part  where  the  vena  cava  passes 
through  the  tendon  is  practically  stationary 
during  normal  respiration.  In  deep  inspiration, 
however,  both  this  part  as  well  as  the  rest  of 
the  pericardial  attachment  is  forcibly  depressed 
towards  the  abdomen.  In  quiet  breathing, 
when  observed  by  the  Rontgen  rays,  the  mean 
descent  of  the  right  dome  in  inspiration  has 
been  found  to  be  about  12-5  mm.,  and  of  the 
left  dome  12  mm.  We  may  say,  roughly,  that 
the  average  descent  of  the  diaphragm  during 
normal  respiration  is  about  half  an  inch, 
intra-abdominal  pressure  play  an  important 
the  movement  of  the  diaphragm,  and  especially  in  preserving  the 
abduction  of  the  lower  ribs  and  so  furnishing  a  fixed  point  for  the 
muscular  fibres  of  the  diaphragm.  If  the  contents  of  the  abdomen 
are  removed  from  a  living  animal  the  ribs  are  drawn  inwards  every  time 
the  diaphragm  contracts.  In  children  with  weak  chest  walls  and  with 
respiratory  obstruction  we  may  often  see  a  depression  round  the  lower 
part  of  the  chest  corresponding  to  the  lower  border  of  the  lungs.  It 
corresponds  to  the  line  at  which  the  diaphragm  leaves  the  chest  wall, 
so  that  the  distending  force  of  the  abdominal  pressure  on  the  bony  walls 
of  the  thorax  abniptly  gives  place  to  the  pull  of  the  distended  lung. 
The  contraction  of  the  diaphragm  lasts  four  to  eight  times  longer 
than  a  simple  contraction  or  muscle-twitch.  It  may  be  regarded 
therefore  as  a  short  tetanus. 

The  enlargement  in  the  other  diameters  is  effected  by  an  elevation 
of  the  ribs.  Each  pair  of  corresponding  ribs,  which  are  articulated 
behind  with  the  spinal  column  and  in  front  with  the  sternum,  forms 


Fig.  487.     Diagram  show- 
ing movements  of  dia- 
phragm in  respiration. 
i  i,  inspiratory  position  ; 

e   e.    expiratory   position. 

(Yeo.) 

The  viscera  and   the 
part   in   determining 


1166  PHYSIOLOGY 

a  ring  directed  obliquely  from  behind  downwards  and  forwards.  With 
each  inspiratory  movement  the  ribs  are  raised,  the  obliquity  becomes 
less,  and  the  horizontal  distance  between  sternum  and  spinal  column 
is  therefore  increased.  Moreover  the  ribs  from  the  first  to  the  seventh 
increase  in  leng-th  from  above  downwards,  so  that  when  they  are 
raised,  the  sixth  rib,  for  instance,  occupies  the  situation  previously 
taken  by  the  fifth,  and  the  transverse  diameters  of  the  thorax  at  this 
height  are  increased.  With  each  inspiration  there  is  a  rotation  of  the 
ribs.  In  the  expiratory  condition  they  are  so  situated  that  their 
outer  surfaces  are  directed  not  only  outwards  but  also  downwards. 
As  they  are  raised  by  the  inspiratory  movements,  they  rotate  on  an 
axis  directed  through  the  fore  and  hind  ends  of  the  rib,  so  that  their 
outer  surfaces  are  turned  directly  outwards.  In  this  way  a  certain 
enlargement  of  the  thoracic  cavity  is  produced.  As  the  thorax  is 
raised  there  is  always  some  stretching  of  the  rib-cartilages. 

In  expiration  the  processes  are  reversed,  and  the  cavity  of  the 
thorax  is  diminished  in  all  three  dimensions. 

The  movements  of  the  thorax  are  effected  by  means  of  muscles. 
Inspiration  is  performed  by  the  following  muscles  : 

The  diaphragm,  which  is  the  most  important,  and  almost  suffices 
alone  to  carry  out  quiet  respiration. 

The  external  intercostal  muscles,  which  shorten  and  so  raise  the 
ribs. 

The  serratus  posticus  superior. 

It  is  probable  that  an  important  part  is  played  even  under  normal 
circumstances  in  the  respiratory  movements  by  the  extension  of  the 
spinal  column.  This  movement,  which  is  specially  marked  at  the 
upper  part  of  the  thorax,  causes  an  increase  in  all  three  diameters  of  this 
cavity.  The  levatores  costarum,  which  are  often  included  in  inspiratory 
movements,  are  so  inserted  into  the  ribs  as  to  be  unable  to  influence 
their  movements.  They  are  concerned,  not  in  respiration,  but  in 
lateral  movements  of  the  spine. 

These  muscles  are  the  only  ones  normally  engaged  in  carrying  out 
inspiration.  When,  in  consequence  of  muscular  exertions  or  from 
any  other  cause,  the  inspiratory  efforts  become  more  forcible,  a  large 
number  of  accessory  muscles  are  brought  into  play.     These  are  : 

The  scaleni, 

Sterno-mastoid, 

Trapezius, 

Pectoral  muscles, 

Rhomboids,  and 

The  serratus  anticus. 

Normal  expiration  is  chiefly  effected  passively.  When  the  in- 
spiratory muscles  cease  to  contract,  the  lungs,  which  were  stretched 


MECHANICS  OF  RESPIRATORY  MOVEMENTS       11G7 

by  the  previous  inspiration,  contract  by  virtue  of  the  elastic  tissue 
they  contain,  and  the  thorax  itself  sinks  by  its  o^\ti  weight,  and  bv 
the  elastic  reaction  of  the  stretched  costal  cartilages. 

It  must  be  remembered,  however,  that  in  a  position  of  rest  the 
elasticity  of  the  thorax  is  opposed  to  the  elasticity  of  the  lunr's. 
Elasticity  of  the  chest  wall  would  therefore  tend  to  produce  inspiration. 
This  factor  would  tend  to  make  inspiration  easier  at  its  onset,  but 
would  also  present  an  impediment  to  the  carrying  out  of  expiration, 
so  that  towards  the  end  of  this  act  there  is  need  for  the  active  co-opera- 
tion of  muscular  contractions.  It  seems  possible  that  more  or  less 
muscular  activity  of  the  expiratory  muscles  is  alternated  ^vith  that  of 
the  inspiratory  muscles.  In  fact  Sherrington's  results  on  the  co- 
ordination of  muscular  movements  would  tend  to  make  us  assume 
inhibition  of  the  tone,  e.g.  of  the  abdominal  muscles,  during  inspira- 
tion, and  active  augmentation  of  their  tone  during  expiration.     Where 


Fig.  488. 


Fiu.  489. 


the  tone  of  the  muscles  is  entirely  lost,  e.g.  in  the  condition  of  viscero- 
ptosis, it  has  been  observed  that  the  diaphragm  is  thrown  out  of  action, 
breathing  being  chiefly  carried  out  by  an  elevation  of  the  upper  part 
of  the  thorax.  Probably  under  normal  circumstances  the  internal 
intercostal  muscles  also  contract  with  each  expiration. 

Although  the  action  of  the  intercostal  muscles  has  been  a  subject  of  debate, 
physiological  experiments  serve  on  the  whole  to  confirm  the  view  first  put 
forward  by  Hamberger  and  based  on  a  consideration  of  the  direction  of  the 
fibres.  The  external  intercostals  pass  from  one  rib  to  the  next  below  down- 
wards and  forwards.  Hence  if  a  pair  of  ribs  be  isolated  from  the  rest  of  the 
chest  wall,  leaving  the  vertebral  and  costal  attachments  intact,  contraction  of 
these  muscles  will  cause  a  rise  of  both  ribs.  This  result  wiU  be  evident  from 
a  consideration  of  Fig.  488,  where  ah  is  a  fibre  of  the  external  intercostal  muscles, 
passing  from  the  rib  vs  to  be  attached  to  the  rib  v's'  at  h.  When  ah  contracts, 
the  tension  it  exerts  on  its  two  attachments  can  be  r&solved  into  two  components 
ac  acting  downwards  and  hd  acting  upwards,  hd,  however,  acts  at  the  end  of 
the  long  lover  hv',  whereas  ac  acts  at  the  end  of  a  short  lever  av.  Hence  the 
raising  effect  will  overcome  the  depressing  effect,  and  both  ribs  will  rise. 

The  fibres  of  the  internal  intercostals  run  in  the  opposite  direction  to  the 
external  muscles,  and  from  a  consideration  of  Fig.  489  it  is  evident  that  their 
effect  will  be  to  depress  any  pair  of  ribs,  thus  acting  as  expiratory  muscles. 

Owing  to  the  fact  that  the  costal  cartilages  make  an  angle  with  the  bony 


1168  PHYSIOLOGY 

ribs,  the  fibres  of  prolongation  of  the  internal  intercostals,  mnsculi  intercartilaginei' 
have  the  same  relation  to  their  attachments  that  the  external  intercostals  have 
to  the  bony  ribs.  Their  action  therefore  must  be  to  raise  the  cartilages  and 
flatten  out  the  angle  between  the  cartilaginous  and  bony  ribs  so  that  they  must 
act  with  the  external  intercostals  as  inspiratory  muscles. 

In  forced  expiration  a  large  number  of  muscles  may  take  part — - 
such  as  the  serratus  posticus  inferior,  and  the  muscles  forming  the 
wall  of  the  abdomen,  i.e.  the  rectus,  obliquus,  and  transversus 
abdominis  muscles. 

As  the  lungs  are  distended  with  each  inspiration  their  position 
changes  in  relation  to  the  thoracic  wall.  All  parts  are  not  equally 
distensible  in  the  normal  position  of  the  lungs.  There  are  three  areas 
which  are  in  contact  with  the  nearly  stationary  parts  of  the  thoracic  wall 
and  cannot  therefore  be  directly  expanded.  These  are  (1)  the  medias- 
tinal surface  in  contact  with  the  pericardium  and  structures  of  the 
mediastinum  ;  (2)  the  dorsal  surface  in  contact  with  the  spinal  column 
and  with  the  spinal  segments  of  the  ribs  ;  (3)  the  apical  surface  lying 
in  contact  with  the  deep  cervical  fascia  at  the  root  of  the  neck.  The 
roots  of  the  lungs  move  with  inspiration  somewhat  forwards  and 
downwards.  The  front  parts  of  the  lungs  move  downwards  and 
inwards,  so  that  their  inner  borders  in  front  approach  one  another. 
The  extent  and  boundaries  of  the  lungs  can  be  easily  ascertained 
in  the  living  subject  by  means  of  percussion.  On  tapping  the  finger 
laid  on  the  chest  a  sound  is  emitted  which  varies  with  the  nature  of  the 
subjacent  tissues.  If  this  is  lung- tissue  filled  with  air,  a  clear  resonant 
tone  is  obtained  ;  where  it  is  solid  tissue,  such  as  the  heart,  or  a  lung 
consolidated  with  inflammatory  products,  or  the  liver,  a  dull  sound 
is  obtained.  It  is  easy  to  show  that  the  resonant  area  of  the  chest 
increases  with  each  inspiration.  The  apices  of  the  lungs  extend  about 
one  inch  above  the  clavicle  anteriorly  and  behind  reach  as  high  as  the 
seventh  spinous  process.  During  moderate  expiration  the  lower  margin 
of  the  lungs  extends  in  front  from  the  upper  border  of  the  sixth  rib  at 
its  insertion  to  the  sternum,  and  runs  obliquely  downwards  to  the  level 
of  the  tenth  rib  at  the  back  of  the  chest.  During  the  deepest  inspiration 
the  lungs  descend  in  front  to  the  seventh  intercostal  space  and  behind 
to  the  eleventh  rib,  while  during  deepest  possible  expiration  the 
lower  margins  of  the  lungs  are  elevated  almost  as  much  as  they  descend 
during  inspiration.  In  the  front  of  the  chest  a  triangular  space  can 
be  always  marked  out  over  the  heart  where  the  note  obtained  on  per- 
cussion is  dull.  This  space  is  bounded  on  the  right  by  the  left  border 
of  the  sternum  and  extends  out  as  far  as  the  cardiac  apex,  being  bounded 
above  by  the  fourth  costo-sternal  articulation  and  below  by  the  sixth 
costal  cartilage. 

BREATH  SOUNDS.     If  the  ear  be  applied  to  the  chest  wall,  either 
directly  or  through  the  medium  of  a  stethoscope,  each  inspiration  is 


MECHANICS  OF  RESPIRATORY  MOVEMENTS        1109 

found  to  be  accompanied  by  a  fine  rustling  sound,  the  '  vesicular  mur- 
mur.' It  is  thought  to  be  caused  by  the  sudden  dilatation  of  the  air- 
vesicles  during  inspiration  or  perhaps  by  the  current  of  air  passing  from 
the  narrow  terminal  bronchioles  into  the  wider  infundibula.  It  is  impor- 
tant to  remember  that  this  sound  is  heard  only  during  inspiration  and 
over  healthy  lungs.  On  listening  over  the  larger  air-passages,  i.e.  the 
larynx,  trachea,  and  bronchi,  we  hear  a  much  louder  sound  which 
accompanies  both  expiration  and  inspiration  and  may  be  compared  to 
a  sharp  whispered  hah.  This  is  known  as  the  '  bronchial  murmur,' 
It  can  be  heard  also  at  the  back  of  the  chest  between  the  scapulae  at 
the  level  of  the  fourth  dorsal  vertebra,  where  the  trachea  bifurcates. 
In  all  other  parts  of  the  chest  the  healthy  lung  prevents  the  propaga- 
tion of  this  sound  to  the  chest  wall.  If,  however,  the  lung  is  solid, 
as  occurs  in  pneumonia,  it  conducts  the  sound  easily  from  the  large 
air-tubes  to  the  chest  wall.  Bronchial  breathing  at  any  part  of  the 
chest  other  than  that  immediately  over  the  air-tubes  is  therefore  a 
distinctive  sign  of  consolidation  of  the  lung.  Absence  of  breath- 
sounds  at  any  part  of  the  chest  implies  either  that  air  is  not  entering 
that  part  of  the  lung,  or  that  the  lung  is  separated  from  the  chest  wall 
by  effused  fluid. 

INTRATHORACIC  PRESSURE.    Even   at   the   end   of   expiration 
the  luno;s  are  in  a  stretched  condition.    This  is  shown  bv   the   fact 
that  if  in  an  animal  or  in   the  corpse  an  opening   be   made   into 
the  pleural  cavity,  air  rushes  into  the  opening  and  the  lungs   col- 
lapse,  driving  a   certain  amount  of  air  out  through  the  trachea. 
Since  the  lungs  are  always  tending  to  collapse,  it  is  evident  that 
they   must   exert   a   pull   on   the   thoracic   wall.     This   pull   of   the 
lungs  gives  rise  to  a  negative  pressure  in  the  pleural  cavity.     If  we 
connect  a  mercurial  manometer  with  the  pleural  cavity,  we  find  that 
the  pull  of  the  lungs  amounts  in  the  corpse  to  6  mm.  of  mercury.     If 
the  lungs  are  fully  distended,  as  after  full  inspiration,  the  elastic 
forces  are  more  brought  into  play,  and  the  negative  pressure  in  the 
pleura  may  amount  to  30  mm.     Since  the  lungs  are  always  tending 
to  collapse,  respiration  becomes  impossible  directly  free  openings  are 
made  into  the  pleural  cavities  on  both  sides.     With  each  inspiratory 
movement  air  rushes  in  through  these  openings,  so  that  the  thoracic 
movements  can  no  longer  exert  any  influence  on  the  volume  of  the 
lungs.     The  negative  pressure  in  the  thorax  is  diminished  by  any 
factor  decreasing  the  elasticity  of  the  lung-tissue.     Thus  in  an  old 
man,  where   the   elastic   tissue   is   degenerated   and  the  alveoli   are 
enlarged,  giving  rise  to  the  condition  known  as  emphysema,  the  lungs 
may  collapse  only  slightly  or  not  at  all  on  opening  the  chest.     The 
lungs  do  not  collapse  on  making  an  opening  in  the  chest  of  a  new-born 
manuual  ;    but  this  is  owing  to  the  fact  that  they  completely  fill  the 

74 


1170  PHYSIOLOGY 

thorax  in  the  expiratory  position,  and  it  is  only  later  that,  with  the 
growth  of  the  ribs,  the  thorax  gets,  so  to  speak,  too  large  for  the  lungs, 
which  are  therefore  stretched  to  fill  it. 

The  force  exerted  by  the  inspiratory  muscles  is  nearly  all  spent  in 
overcoming  the  elastic  resistance  of  the  lungs  and  costal  cartilages. 
A  free  access  of  air  is  provided  for  by  contractions  of  certain  accessory 
muscles  of  respiration.  With  each  inspiration  the  glottis  is  widened 
by  abduction  of  the  vocal  cords.  When  the  glottis  is  observed  by 
means  of  the  laryngoscope,  a  rhythmical  separation  and  approximation 
of  the  vocal  cords  are  observed,  synchronous  respectively  with  inspira- 
tion and  expiration  (Fig.  253,  p.  583).  When  inspiration  is  laboured, 
the  alse  nasi  are  dilated  by  the  action  of  the  dilatator  nasi.  This 
movement  of  the  nostril,  which  is  constant  in  many  animals,  becomes 
very  marked  in  children  suffering  from  any  respiratory  trouble. 

If  a  manometer  be  connected  with  one  of  the  nostrils,  so  as  to  register 
the  pressure  in  the  air-cavities,  it  is  found  that  there  is  a  negative 
pressure  of  —  1  mm.  Hg.  with  inspiration,  and  a  positive  pressure  of 
2  or  3  mm.  with  expiration.  Wiih  forced  inspiration  the  negative 
pressure  may  amount  to  —  57  mm.  Hg.,  and  with  forced  expiration 
there  may  be  a  positive  pressure  of  +  87  mm. 

PULMONARY  VENTILATION.  Under  no  circumstances  can 
we  by  forced  expiration  empty  the  lungs  of  air.  At  the  end  of 
the  most  forcible  expiration,  if  the  pleura  were  perforated,  the 
lungs  would  collapse  and  drive  more  air  through  the  trachea. 
When  breathing  quietly  a  man  takes  in  and  gives  out  at  each 
breath  about  500  c.c.  of  air,  measured  dry  and  at  0°  C.  If  measured 
moist  and  at  the  temperature  of  the  body,  viz.  37°  C,  the  volume 
would  be  about  600  c.c.  This  amount  is  known  as  the  tidal  air.  By 
means  of  a  forcible  inspiratory  effort  it  is  possible  to  take  in  about 
1500  c.c.  more  {comflemental  air).  At  the  end  of  a  normal  expiration 
a  forcible  contraction  of  the  expiratory  muscles  will  drive  out  about 
1500  c.c.  more  {supplemental  air).  These  three  amounts  together 
constitute  the  '  vital  capacity  '  of  an  individual.  This  total  may  be 
determined  by  means  of  the  instrument  known  as  the  spirometer, 
which  is  merely  a  small  gas-meter  with  a  gauge  by  which  the  amount 
of  air  in  it  can  be  at  once  read  off.  The  person  to  be  tested  fills  his 
lungs  as  full  as  possible,  and  then  expires  to  the  utmost  into  the  spiro- 
meter. The  air  left  in  the  lungs  after  the  most  vigorous  expiration 
is  known  as  the  residual  air. 

The  residual  air  may  be  determined  by  letting  a  person  expire  tc  the  utmost 
extent  and  then  connecting  with  his  mouth  or  nose  a  bag  of  known  capacity 
filled  with  hydrogen.  The  subject  of  thc^  experiment  then  inspires  and  expires 
into  the  bag  two  or  three  times,  ending  in  the  same  state  of  forced  expiration 
as  he  began.     Any  diminution  of  the  total  volume  of  gas  in  the  bag  will  rejjresent 


MECHANICS  OF  RESPIRATORY  MOVEMENTS       1171 

the  gas  lost  during  the  experiment  by  diflfusion  into  the  blood-vessels.  By  analysis 
of  the  gaseous  mixture  in  the  bag,  it  is  possible  to  determine  the  amount  of  air 
in  the  lungs  at  the  beginning  of  the  experiment.  Supposing,  for  example,  the 
bag  held  4000  c.c.  hydrogen,  after  two  respirations  the  total  volume  is  unaltered, 
but  the  gas  is  foimd  to  consist  of  3000  c.c.  h3'drogen  and  1000  c.c.  oxj'gen,  nitrogen, 
and  CX32,  i.e.  pulmonary  gases.  Since  the  gas  in  the  Imigs  must  have  the  same 
composition  and  1000  c.c.  hydrogen  have  disappeared  from  the  bag,  it  is  evident 
that  the  lungs  \vill  contain  1000  c.c.  hAxlrogen  and  — ;"— ,  i.e.  330  c.c.  pulmonary 
gases.  Thus  the  total  volume  of  gas  left  in  the  limgs  at  the  end  of  the  forced 
expiration  was  1330  c.c.,  which  is  the  residual  volume  for  the  individual. 

The  above  example  is  purely  imaginary.  As  a  result  of  actual 
determinations  carried  out  we  may  assume  the  residual  air  in  the  lungs 
as  something  between  600  and  1200  c.c. 

Of  the  500  c.c.  of  tidal  air  taken  in  at  each  inspiration,  only  a  certain 
part  reaches  the  alveoli,  part  being  required  to  fill  the  air -tubes,  trachea, 
bronchi,  and  bronchioles  which  lead  to  the  air-cells.  The  volume  of 
the  air-tubes  has  been  reckoned  to  amount  to  1-40  c.c,  so  that  of  the 
500  c.c.  about  360  c.c.  reach  the  alveoU.  For  the  same  reason  the 
expired  air  represents  the  air  from  the  alveoli  (360  c.c.)  diluted  with 
140  c.c.  of  air  which  has  remained  in  the  air-tubes  and  undergone 
very  Uttle  change,  other  than  the  elevation  of  temperature  and  satura- 
tion with  aqueous  vapour.  We  have  therefore  to  allow  for  this  air 
contained  in  the  so-called  '  dead  space  '  of  the  lungs  when  we 
seek  to  arrive  at  the  composition  of  alveolar  air  from  an  analysis  of 
expired  air. 


SECTION  II 

THE  CHEMISTRY  OF  RESPIRATION 

The  energy  of  the  body  is  derived  almost  entirely  from  the  oxidation 
of  the  carbon  and  hydrogen  of  the  food-stuffs.  An  adult  man  during 
the  twenty-four  hours  produces  on  the  average  250  c.c.  of  carbon 
dioxide  per  kilo  per  hour.  A  man  of  60  kilos  will  therefore  excrete 
250  X  60  X  24  =  360,000  c.c.  carbon  dioxide  in  the  course  of  twenty- 
four  hours.  During  sleep  the  output  of  carbon  dioxide  is  lowered 
with  the  diminution  in  all  the  metaboUc  processes  of  the  body  and 
amounts  to  only  160  c.c.  per  kilo  per  hour.  If  we  assume  that  eight 
hours  of  the  twenty-four  are  given  to  sleep,  this  will  leave  295  c.c. 
per  kilo  per  hour  as  the  average  excretion  of  carbon  dioxide  during 
the  waking  hours.  Since  the  access  of  oxygen  to  the  body  and  the 
removal  of  carbon  dioxide  is  effected  by  the  pulmonary  ventilation, 
the  expired  air  will  differ  from  the  inspired  air  in  containing  more 
carbon  dioxide  and  less  oxygen.  The  oxygen  intake  is  not,  however, 
absolutely  proportional  to  the  carbon  dioxide  output.  This  is  owing 
to  the  fact  that  carbon  is  not  the  only  element  which  leaves  the  body 
in  an  oxidised  condition.  Fats,  for  example,  contain  a  number  of 
unoxidised  atoms  of  hydrogen,  which  in  the  metabolic  processes  of 
the  body  are  fully  oxidised,  to  be  excreted  as  water.  Oxygen  will 
also  leave  the  body  in  combination  with  carbon  and  nitrogen  in  the 
urine,  so  that  a  certain  amount  of  oxygen  which  is  taken  in  does  not 
reappear  as  carbon  dioxide  in  expired  air.  There  is  thus  an  absolute 
diminution  in  the  volume  of  expired  air  as  compared  with  that  of 
inspired  air.  This  diminution,  due  to  loss  of  oxygen,  is  greater  in 
carnivora,  whose  food  consists  mainly  of  proteins  and  fats,  than  in 
herbivora,  which  feed  principally  on  carbohydrates,  and  depends  on 

1  .     COo  expired 

the  respiratory  quotient,  i.e.  the  ratio  — - — r-^^-. — t~ 

O2   inspired. 

In  man  the  average  respiratory  quotient  can  be  taken  as  0*85. 

On  this  basis  the  amount  of  oxygen  which  will  be  taken  in  during 

the  waking  hours  will  be  347  c.c.  per  kilo  per  hour.    Taking  round 

figures,  we  may  say  that,  when  awake,  a  man  takes  in   350  c.c. 

oxygen  and  gives  out  300  c.c.  carbon  dioxide  per  kilo  per  hour. 

From  these  figures  we  can  calculate  the  normal  composition  of  expired 

air  when  a  man  is  breathing  quietly.      Under  these  conditions  the 

1172 


THE  CHEMISTRY  OF  RESPIRATION  1 1  T". 

tidal  air  amounts  to  500  c.c.  If  he  breathes  seventeen  times  a  minute 
the  total  pulmonary  ventilation  during  the  hour  will  be  500  x  17  x  60 
=  510,000  c.c.  per  hour.  This  will  contain  300  x  70  c.c.  =  21,000  c.c. 
carbon  dioxide.  Hence  the  percentage  of  carbon  dioxide  in  the 
expired  air  will  be  4'1  per  cent.  In  the  same  Avay  we  can  reckon  the 
percentage  of  oxygen  in  the  expired  air  at  16"4  per  cent.  Exact 
experiments  have  shown  that  the  volume  of  nitrogen  is  unchanged 
during  respiration,  this  gas  taking  no  part  in  the  ordinary  metabolic 
processes  of  the  body.  We  may  therefore  compare  the  ordinary 
composition  of  inspired  and  expired  air  as  follows  : 


Inspired  Air 

Oxygen . 

20'96  vola.  per  cent, 

Nitrogen  and  ar 

gon 

79-00 

Carbon  dioxide 

Expired  Air 

0-04 

Oxygen . 

16-4  vols,  per  cent. 

Nitrogen 

79-5 

Carbon  dioxide 

. 

41 

The  increase  in  the  figures  for  nitrogen  refers  of  course  only  to  the 
percentage  amount,  since  the  total  volume  of  air  breathed  is  decreased 
by  the  disappearance  of  a  certain  amount  of  oxygen  without  the  pro- 
duction of  a  corresponding  amount  of  carbon  dioxide,  so  that  the 
relative  amount  of  nitrogen  is  slightly  increased.  These  figures  for 
the  composition  of  inspired  and  expired  air  refer  to  dry  air  at  a  tempera- 
ture of  0°  C.  and  a  pressure  of  760  mm.  Under  normal  circumstances 
inspired  air  contains  a  variable  amount  of  aqueous  vapour  and  has 
a  variable  temperature  corresponding  with  the  time  of  year.  Expired 
air  is  fully  saturated  with  aqueous  vapour  and  has  the  temperature 
of  the  body,  37°  C.  The  aqueous  vapour  at  this  temperature  is  by 
no  means  negligible.  Its  tension  amounts  to  50  mm.  Hg.  Thus 
when  a  man  is  breathing  dry  air  at  a  pressure  of  760  mm.  Hg.,  the 
pressure  of  the  mixture  of  gases  in  the  alveoli  of  his  lungs  will  be  only 
760  -  50,  i.e.  710  mm.  Hg. 

Only  a  certain  percentage  of  the  500  c.c.  of  tidal  air  reaches  the 
alveoli,  100  to  140  c.c.  being  required  to  fill  the  trachea  and  bronchial 
tubes.  Hence  the  alveolar  air  must  contain  more  carbon  dioxide 
and  less  oxygen  than  the  tracheal  air  ;  and  it  is  found  that,  if  we  take 
the  air  from  the  alveoli  instead  of  that  expired  through  the  mouth  or 
nose,  the  differences  between  it  and  the  inspired  air  are  much  more 
pronounced. 

A  sample  of  alveolar  air  may  be  obtained  for  analysis  in  the  following  way 
(Haldane) :  A  piece  of  india-rubber  tubing  is  taken  of  about  1  inch  diameter 
and  4  feet  long.     Into  one  end  (Fig.  490)  is  fitted  a  mouthpiece,  the  other  being 


1174  PHYSIOLOGY 

left  open  or  connected  with  a  spirometer.  About  2  inches  from  the  mouthpiece 
is  fixed  a  gas  sampling-bulb,  which  is  provided  with  three-way  taps  at  the  upper 
and  lower  ends.  Before  an  experiment  the  bulb  is  filled  with  mercury,  if  the 
lower  end  is  open,  or  else  it  is  completely  exhausted.  The  subject  of  the  experi- 
ment, after  breathing  normally  a  few  times,  at  the  end  of  a  normal  inspiration 
puts  his  mouth  to  the  tube,  expires  quickly  and  deeply,  and  closes  the  mouth- 
piece with  his  tongue.  The  tap  of  the  sampling-bulb  is  then  tiurned,  and 
the  air  last  expelled  from  the  lungs  (which  is  therefore  piue  alveolar  air) 
rushes  into  the  J>ulb.  The  tap  of  the  bulb  is  then  turned  off,  and  the  gas 
may  be  removed  for  analysis.  A  similar  sample  is  then  taken,  in  which 
the  subject  expires  deeply  at  the  end  of  a  normal  expiration.  This  sample 
will,  of  coxu-se,  contain  more  CO2  and  less  O2  than  that  obtained  at  the  end 


S/IMPL/A/G    TUBE. 


Fig.  490. 

of  mspiration.     The  mean  of  the  two  samples  is  taken  as  the  average  composi- 
tion of  alveolar  air. 

The  difference  between  the  composition  of  expired  air  and  alveolar 
air  is  determined  by  the  dilution  of  the  alveolar  air  with  that  contained 
in  the  dead  space.  Hence  with  shallow  breathing  there  will  be  a  large 
difference,  but  this  will  decrease  with  increased  depth  of  respiration. 
Thus,  if  the  alveolar  air  contained  6  per  cent.  CO2  and  the  dead  space 
amounted  to  150  c.c,  the  expired  air  would  only  contain  3  per  cent. 
COo  when  the  person  was  taking  in  only  300  c.c.  at  each  respiration. 
If,  however,  he  was  breathing  slowly  and  deeply  so  as  to  raise  the  tidal 
air  to  1500  c.c,  only  one-tenth  of  this  would  be  represented  by  the 
dead  space,  and  the  expired  air  would  contain  nine-tenths  as  much 
CO2  as  the  alveolar  air,  i.e.  5*4  per  cent. 

The  changes  in  the  composition  of  alveolar  air  with  respiration 
are  by  no  means  so  marked  as  those  produced  in  the  tidal  air,  since 
the  latter  forms  only  a  small  proportion  of  the  total  air  in  the  lung 
alveoli.  Thus  at  the  end  of  a  normal  expiration  the  alveoli  still  contain 
2500  c.c.  of  gases.  In  inspiration  360  c.c.  atmospheric  air  is  taken 
into  this  space  and  mixed  with  the  2500  c.c.  already  there.  The 
'  ventilation  coefficient '  in  quiet  breathing  is  therefore  only  one-seventh, 
and  the  change  in  the  oxygen  and  carbon  dioxide  content  of  the 
alveolar  air  produced  by  this  access  of  360  c.c.  will  amount  to  less 
than  one-half  per  "cent.  This  is  illustrated  by  the  following  figures 
from  Haldane,  giving  the  alveolar  content  in  carbon  dioxide  at  the 
end  of  inspiration  and  at  the  end  of  expiration  respectively. 


THE  CHEMISTRY  OF  RESPIRATION 

Alveolar   CO.,  Tensions. 


1175 


Iinlividual 

Alveolar  CO,  at  end  of 
iiispirutioii.     (Jrcan  of 
twelve  observations) 

CO,  at  end  of 
expiration 

Mean 

J.  S.  H. 
J.  G.  P. 

5-54 
617 

5-70 
6-39 

5-62 
6-28 

We  can  thus  speak  of  an  average  composition  of  alveolar  air  which, 
in  spite  of  the  constant  ventilation,  differs  from  the  external  air  in 
containing  an  excess  of  carbon  dioxide  and  a  relative  lack  of  oxygen. 
Lavoisier,  who  was  the  first  to  study  the  chemical  changes  in  respira- 
tion accurately,  regarded  the  lungs  as  the  seat  of  the  formation  of 
carbon  dioxide  and  the  consumption  of  oxygen.  This  view  was 
generally  accepted  until  it  was  shown  by  Magnus,  in  Heidenhain's 
laboratory,  that  the  blood  passing  to  the  lungs  contained  more  carbonic 
acid  gas  and  less  oxygen  than  that  passing  away  from  the  lungs.  The 
effects  of  this  discovery  were  to  transfer  the  chief  seat  of  oxidation 
to  the  tissues  of  the  body,  and  to  show  that  the  blood  acts  simply  as 
a  carrier  of  the  oxygen  from  the  lungs  to  the  tissues,  and  of  the  carbon 
dioxide  from  the  tissues  to  the  lungs.  We  thus  learnt  to  distinguish 
between  external  and  internal  respiratory  processes.  A  consideration 
of  the  chemical  mechanisms  involved  in  the  process  of  external  respira- 
tion includes  therefore  an  investigation  of  the  manner  in  which  gases 
are  held  by  the  blood  and  of  the  factors  which  are  responsible  for  the 
transfer  of  oxygen  and  carbon  dioxide  from  blood  to  alveolar  air,  and 
from  alveolar  air  to  blood. 

If  blood  be  exposed  to  a  Torricellian  vacuum  at  the  ordinary 
temperature,  the  whole  of  its  contained  gases  is  given  ofi.  For  the 
purpose  of  extracting  the  blood  gases  a  great  variety  of  pumps  have 
been  devised.  In  every  case  a  glass  vessel  is  evacuated  by  means  of 
the  mercury  pump,  and  is  then  put  into  connection  with  a  reservoir 
containing  blood  which  has  been  defibrinated,  or  has  been  prevented 
from  clotting  by  the  addition  of  oxalate  or  citrate.  In  all  these  pumps 
the  main  difl&culty  arises  in  the  exclusion  of  atmospheric  air,  and  it 
is  therefore  important  to  dispense  so  far  as  possible  with  taps.  One 
of  the  best  modifications  of  the  Topler  mercury  pump  is  that  employed 
by  Barcroft  (Fig.  491),  which  differs  little  from  the  pump  devised  by 
Bohr. 

The  construction  of  the  pump  is  shown  in  the  tliagrani.  The  actual  pump 
consists  of  the  parts  a,  b,  c,  d.  Tlic  bulb  b  is  prolonged  below  bj-  a  wide  tube 
dippuig  into  the  mercury  in  the  Woulf  bottle  a.  Tlie  upper  part  of  tiie  bottle 
is  filled  with  water  and  eonheeted  by  two  taps  at  w  with  the  water-supply 
and  with  a  sink.     The  water  being  turned  on,  mercury  is  forced  uji  into  b  ;  as  it 


1176 


PHYSIOLOGY 


rises  into  Y  it  carries  before  it  a  glass  valve  which  prevents  its  fvu-ther  passage, 
so  that  it  can  only  escape  bj'  the  tube  c,  dri%'ing  before  it  all  the  air  previously 
contained  in  B,  The  water-supply  is  now  turned  off,  and  the  tap  to  the  sink 
turned  on.  The  mercury  runs  back.  Air  cannot  enter  by  c,  since  this  tube  is 
sealed  by  mercury.  The  valve  Y  therefore  sinks  and  allows  the  air  in  the  blood 
receivers  G,  g  and  the  rest  of  the  apparatus  to  escape  into  b.  This  process  is  repeated 
many  times  imtil  a  high  vacuum  is  produced  in  the  whole  apparatus.     A  measixred 


>i^t^0^ 


Fig.  491.     Barcroft's  modification  of  the  Topler  pump. 


quantity  of  blood  is  now  let  into  the  lower  bulb  G.  F  is  a  condenser  through  which 
cold  water  is  constantly  flowing  (to  prevent  all  the  blood  boiling  away),  while 
warm  water  circulates  round  the  bulbs  G,  G  to  facilitate  the  giving  off  of  the  blood 
gases.,  The  blood  boils  in  the  vacuum,  and  the  gases  escape  into  B,  and  may  be 
driven  off  and  collected  over  mercury  in  a  cylinder  d  by  raising  the  mercury  in  B. 
The  process  of  exhaustion  is  repeated  until  no  more  bubbles  rise  into  D  on  filling 
the  bulb  B  with  mercury,  e  is  a  sulphuric  acid  chamber  for  drymg  the  gases  as 
they  pass  from  the  blood  to  the  bulb  b. 

In  this  way,  from  100  c.c.  of  blood,  about  60  c.c.  of  mixed  gases 
may  be  obtained,  consisting  of  oxygen,  carbon  dioxide,  nitrogen,  and 


THE  CHEMISTRY  OF  RESPIRATION  1177 

argon.  Argon  is  present  only  in  insignificant  quantities,  about  -04 
volume  per  cent.  The  nitrogen  also  forms  only  between  one  and 
two  volumes  per  cent,  and  is  present  in  the  same  proportion  in  both 
arterial  and  venous  blood.  The  amounts  of  oxygen  and  carbon 
dioxide  in  these  two  kinds  of  blood  differ,  however,  within  wide  limits. 
The  following  Table  represents  the  average  composition  of  the  gases 
obtained  from  an  artery  and  a  vein  of  the  dog  ; 

From  100  vols.  May  b;-  ()})tainccl 


Of  arterial  blood 
Of  venous  blood 


Of  oxygen  Of  carbon  dioxide       Of  nitro(,'cn 

.     20  vols.        .     40  vols.      .      1  lo  2  vols. 
8  to  12  vols.    .     46     „ 

Measured  at  760  mm.  and  O"  C. 


Barcroft  has  sho-4vn  that  the  principle  introduced  by  Haldane  (v.  p.  969) 
for  the  determination  of  the  oxygen  combined  in  the  form  of  oxyhsemoglobin 


«t::l^<= 


BAIRD  &  TATLOC 
(LONDON  1  LV 


Fig.  492.     Barcroft's  blood-gas  apparatus. 
A,  for  1  CO.  ;   B,  for  0-1  c.c.  blood. 


may  be  successfully  applied  to  small  quantities  of  blood,  such  as  1  c.c.  or  even 
0-1  c.c,  and  that  in  the  same  sample  of  blood  the  carbon  dioxide  may  be  deter- 
mined. In  this  way  it  becomes  practicable  to  make  blood-gas  analyses  in  a 
patient,  or  in  experiments  on  small  organs  where  it  is  desired  to  determine  tiieir 
gaseous  metabolism  by  comparhig  the  arterial  with  the  venous  blood.  Tiic 
apparatus  for  dealing  with  1  c.c.  of  blood  is  shown  in  Fig.  492  a. 

The  apparatus  consists  of  two  bottles  of  identical  size  (about  30  c.c.)  attached 
to  a  manometer,  the  tubing  of  which  is  1  mm,  bore.  The  manometer  is  filled 
with  clove  oil  of  knowii  specific  gravity.  To  fi.ll  it  take  out  the  centre  tube, 
put  in  clove  oil  at  a,  put  in  the  centre  tube  with  the  glass  tube  b  open  and  some 
pressure  on  the  rubber  tube  c.  The  oil  should  stand  about  half  way  up  each 
tube;  seal  B  in  a  flame.  The  following  constants  must  be  determined  :  (1)  the 
sectional  area  of  the  tubing  a  ;  (2)  the  size  of  the  bottles  v. 


1178  PHYSIOLOGY 

To  determine  A.  The  centre  tube  x  is  marked  in  one-hundredths  of  a 
cubic  centimetre.  Expel  0-1  c.c.  from  it  into  the  manometer  tubes,  which  are 
of  the  same  size.  0-05  c.c.  will  have  gone  into  each  ;  read  the  difference  in  level. 
From  the  mean  of  a  number  of  such  readings  a  is  directly  deducible. 

To  determine  v.  With  a  knowledge  of  a,  v  may  be  obtained  by  an  application 
of  Boyle's  law.  Fill  the  bottles  almost  full  of  water,  putting,  say,  25  c.c.  of  water 
in  each,  shut  one  of  the  taps,  keeping  the  other  open.  Tighten  the  screw  so  as 
to  produce  a  knoAvn  compression  on  the  closed  side  ;  observe  the  difference  of 
pressiu-e  produced.  The  tubes  should  be  moistened  with  oil  before  the  experiment 
commences. 

To  determine  the  oxygen  capacity  of  a  sample  of  blood.  Place  2  c.c.  of  ammonia 
solution  (made  by  adding  4  c.c.  of  strong  NHg  to  a  litre  of  water)  in  one  of  the 
bottles  and  add  1  c.c.  of  blood.  Thoroughly  lake  the  blood.  Put  vaseline  on  the 
large  and  small  stoppers.  Put  0-2  c.c.  of  a  satiu'ated  solution  of  potassium 
ferricyanide  in  the  small  tube  contained  in  the  stopper  of  the  bottle  containing 
the  blood  (this  is  best  done  with  a  fuie  pipette  which  goes  down  these  tubes). 
Put  in  the  small  stopper.  Place  the  apparatus  on  the  side  of  a  large  water  bath 
(such  as  a  pail)  with  both  taps  open.  In  about  five  minutes  close  the  tap  on  the 
side  of  the  blood  and  rotate  the  bottle  on  the  stopper  till  the  ferricyanide  trickles 
into  the  laked  blood.  Shake  thoroughly,  replace  in  the  bath,  and  repeat  this 
several  times  till  a  constant  difference  of  level  is  obtained.  By  means  of  the  screw 
clamp  bring  the  column  of  oil  on  the  side  of  the  blood  to  its  original  level,  and  then 
measm-e  the  difference  of  level  between  the  two  sides.  Let  this  difference  of 
level  be  y  mm.  ;  let  p  be  the  height  of  the  barometer  in  millimetres  of  clove  oil, 

and  X  the  volume  of  oxygen  given  off  in  cubic  millimetres  ;  then  x  =  y  {  —  !• 

Except  in  the  most  exact  work  p  may  be  taken  as  10,000  mm.,  in  which  case  the 

V 
expression  —  maybe  determined  once  for  all  and  called  C,  the  constant  of  the 

apparatus  :    then  x  =  y  x  C. 

To  determine  the  gaseous  contents  of  a  given  blood.  If  we  wish  to  determine 
the  actual  amount  of  oxygen  as  oxj^hsemoglobin  in  the  sample,  the  blood  must  be 
carefully  introduced  so  as  to  lie  below  the  ammonia  and  not  to  come  in  contact 
with  the  air.  The  stopper  is  then  replaced  in  the  bottle  and  immersed  in  the 
bath,  with  both  taps  open  until  it  has  attained  a  constant  temperature.  The  tap 
is  then  closed  and  the  height  of  the  column  of  oil  noted.  The  blood  is  then 
laked  by  rotating  the  apparatus,  and  after  allowing  five  minutes  for  complete 
laking  the  ferricyanide  is  run  in.  The  rest  of  the  determination  is  carried  out  as 
above. 

The  carbon  dioxide  may  be  determined  in  the  same  sample  of  blood  by  running 
in  tartaric  acid  in  the  same  way  as  potassium  ferricj'anide  was  previously  run  in. 
It  is  necessary  always  to  determine  the  oxygen  before  the  carbon  dioxide,  since 
the  mere  acidification  of  the  blood  causes  the  evolution  of  a  certain  amount 
of  oxygen.  The  results  obtained  for  carbon  dioxide  are  not  so  accurate  as  those 
for  the  oxygen,  owing  to  the  larger  error  introduced  by  the  increased  solubility 
of  this  gas  in  watery  media. 

The  same  apparatus  may  be  used  as  a  differential  blood-gas  manometer,  where 
it  is  desired  to  compare  the  oxygen  contents  of  two  samples  of  blood,  e.g.  of  arterial 
and  venous  blood.  For  this  purpose  1  c.c.  of  the  arterial  blood  is  introduced 
into  one  bottle  and  1  c.c.  of  the  venous  blood  into  the  other  bottle,  in  each  case 
under  1^  c.c.  of  weak  ammonia.  The  bottles  are  then  placed  on  the  apparatus 
and  immersed  in  the  water  bath  until  no  change  occurs  in  the  height  of  the 
column  of  oil.  The  two  taps  are  then  closed  and  the  apparatus  is  vigorously 
shaken.     The  blood  on  each  side  is  laked,  and  in  contact  with  the  air  in  the  bottles 


THE  CHEMISTRY  OF  RESPIRATION 


1179 


becomes  completely  saturated  with  oxygen.  No  carbon  dioxide  is  given  oflF, 
since  thi«  combines  with  the  weak  ammonia.  If  the  two  bloods  contain  the  same 
amount  of  oxyhajmoglobin  no  difference  will  be  produced  in  the  level  of  the  oil 
in  the  two  tubes.  If,  however,  one  be  arterial  and  the  other  venous,  the  venous 
blood  will  absorb  more  oxygen  from  its  bottle  than  the  arterial  blood  from  its 
side  of  the  apparatus,  so  that  the  oil  will  rise  in  the  tube  on  the  side  of  the 
venous  blood.  From  the  amount  of  rise  the  diflFerence  in  the  amount  of 
oxygen  taken  up  by  the  blood  on  the  two  sides  can  be  reckoned,  and  this  figure 
will  express  the  relative  satiu-ation  of  the  haemoglobin  in  the  two  samples  of 
blood. 

For  clinical  purposes  it  is  possible  to  work  with  0-1  c.c.  of  blood.  Fig.  492  b 
represents  the  form  of  apparatus  devised  by  Barcroft  for  dealing  with  these 
minute  quantities.  The  principle  of  the  apparatus  is  the  same  as  that  of  the 
larger  type. 

The  condition  of  the  gases  in  the  blood  can  be  judged  by  the 
amount  of  gas  which  the  blood  will  take  up  when  exposed  to  different 
pressures  of  the  gas.  If  a  gas  is  in  simple  solution  the  amount  of  it 
dissolved  varies  directly  with  the  pressure.  Thus,  if  water  takes  up 
a  certain  bulk  of  a  gas  at  a  given  temperatare  and  press  are,  it  will 
take  up  twice  as  much  if  the  pressure  of  the  gas  be  doubled. 
Since  the  volume  of  a  gas  varies  inversely  as  the  pressure,  we  may 
8iy  that  a  fluid  will  dissolve  the  same  volume  of  gas  whatever  the 
pressure.  The  absorption  coefficient  of  a  hquid  for  a  gas  is  expressed 
by  the  number  of  cubic  centimetres  of  gas  which  will  be  taken  up  at 
0°  C.  by  1  c.c.  of  the  liquid  when  the  gas  is  at  a  pressure  of  760  mm. 
Hg.  The  absorption  coefficient  diminishes  with  rise  of  temperature. 
The  following  Table  represents  the  absorption  coefficient  for  oxygen, 
carbon  dioxide,  carbon  monoxide,  and  nitrogen,  in  water  at  various 
temperatures  between  0°  and  40°  C.  : 


Temperature 

Oxygen 

Carbon  dioxide 

Carbon  monoxide 

Xitrogen      . 

0 

00489 

1-713 

00354 

0-0239 

10 

0-0380 

M94 

0-0282 

0-0196 

20 

00310 

0-878 

0  0232 

00164 

30 

00262 

0-665 

00200 

00138 

40 

00231 

0.530 

0-0178 

00118 

From  this  Table  we  see  that  100  c.c.  of  water  at  0°  C.  will  absorb 
489  c.c.  oxygen  at  760  mm.  Hg.,  i.e.  at  one  atmosphere.  If  the 
pressure  be  raised  to  two  atmospheres  the  volume  of  gas  absorbed 
will  be  the  same,  but  if  these  gases  be  measured  at  the  original  pressure, 
i.e.  at  one  atmosphere,  the  amount  dissolved  will  be  9' 78  volumes. 
If  therefore  we  plot  out  the  absoq^tion  of  the  gas  on  a  curve  of  which 
the  ordinates  represent  the  amount  of  gas  dissolved  and  the  abscissa 
the  different  pressures  of  the  gas,  we  shall  find  that  the  curve  is  a 


1180  PHYSI0L0C4Y 

straight  line.  The  relation  between  the  amount  absorbed  is  not 
altered  by  the  presence  of  other  gases  at  the  same  time.  The  pressure 
of  the  whole  atmosphere  is  760  mm.  Since  the  atmosphere  consists 
roughly  of  four  parts  of  nitrogen  with  one  part  of  oxygen,  the  atmo- 
spheric pressure  is  due  as  to  one-fifth  to  the  oxygen  and  as  to 
four-fifths  to  the  nitrogen.  If  we  shake  up  water  at  0°  C.  with  the 
atmospheric  air  at  the  ordinary  pressure,  100  c.c.  of  water  will 
absorb  4-89  c.c.  x  1,  and  of  nitrogen  2-39  x  |.  We  may  there- 
fore extend  our  statement  as  to  the  solubihty  of  gases  in  fluids  and 
say  that  the  amount  of  gas  dissolved  in  a  fluid  is  proportional  to  the 
partial  pressure  of  the  gas. 

WTien  water  is  shaken  up  with  a  gas  until  it  will  take  up  no  more, 
i.e.  until  it  is  saturated  for  that  pressure,  a  state  of  equilibrium  exists 
between  the  gas  dissolved  in  the  fluid  and  the  gas  in  contact  with  the 
fluid.  In  this  state  of  equilibrium  the  number  of  molecules  of  the  gas 
entering  the  flaid  is  exactly  equal  to  the  number  of  molecules  of  the 
gas  leaving  the  fluid.  If  we  remove  the  liquid  after  saturation,  say, 
at  one  atmosphere  to  a  vessel  where  it  is  in  contact  with  gas  at  a 
pressure  of  half  an  atmosphere,  the  liquid  will  give  off  gas  until  the 
amount  left  in  solution  is  diminished  to  one-half.  The  gas  dissolved 
in  a  liquid  thus  has  a  pressure  or  tension  which  tends  to  make  it  escape 
from  the  liquid.  The  only  way  in  which  we  can  measure  this  tension 
is  by  finding  what  pressure  of  gas  is  in  exact  equilibrium  with  the 
liquid.  Thus  if  we  take  some  water  containing  carbon  dioxide  in 
solution,  divide  it  into  two  parts,  and  shake  up  one  part  with  a  gaseous 
mixture  containing  4  per  cent,  of  carbon  dioxide  and  the  other  part 
with  a  mixture  containing  5  per  cent,  of  carbon  dioxide,  and  find  that 
the  solution  loses  gas  to  the  former  and  takes  up  carbon  dioxide  from 
the  latter,  we  may  conclude  that  the  tension  of  carbon  dioxide  in  the 
original  fluid  was  somethmg  between  4  and  5  per  cent,  of  an  atmosphere. 
It  is  by  some  such  means  that  the  tensions  of  gases  in  the  blood  are 
measured,  the  instruments  for  this  purpose  receiving  the  name  of 
aerotonometers. 

The  solvent  power  of  water  for  gases  is  diminished  if  the  water 
contains  other  solid  substances  in  solution.  Blood-plasma  or  blood- 
corpuscles  will  therefore  have  a  smaller  solvent  power  for  gases  than 
has  pure  water.  It  has  been  shown  by  Bohr  that  the  depression  of 
solubility  caused  by  the  presence  of  proteins  or  salts  in  solution  is 
t^he  same  for  all  gases.  The  absorption  coefficient  of  blood-plasma 
for  gases  is  reduced  to  97-5  per  cent,  of  pure  water,  and  of  blood 
to  92  per  cent.,  that  of  the  blood -corpuscles  being  as  low  as  81  per 
cent.  We  may  thus  reckon  the  absorption  coefficient  of  blood- 
plasma,  blood,  and  blood-corpuscles,  for  oxygen,  nitrogen,  and 
carbon  dioxide. 


THE  CHEMISTRY  OF  RESPIRATION 


Oxygen 

Xitrdfe'cn 

Carbon  dioxifU; 

15° 

38° 

15° 

38° 

15° 

38° 

Blood-plasma    . 
Blood       . 
Blood-corpuscles 

0033 
0-031 
0-025 

0023 
0-022 
0019 

0017 
0-016 
0-014 

0012 
0011 
0-010 

0-994 
0-937 

0-825 

0-541 
0-511 
0-450 

From  tliis  Tuble  we  see  that  lUO  volumes  of  blood  at  38°  C.  niioht 
contain  2*2  c.c.  of  oxygen  in  solution  if  the  blood  had  been  exposed  to 
oxygen  at  a  pressure  of  one  atmosphere.  The  blood  in  the  lungs  is,  how- 
ever, exposed  to  air  which  contains  only  about  one-sixth  of  its  volume 
of  oxygen,  so  that  the  total  amount  of  oxygen  present  in  arterial  blood 
in  solution  cannot  be  more  than  one-sixth  of  2-2,  i.e.  about  0-36  c.c^ 
per  cent.  Since  arterial  blood,  or  blood  saturated  with  oxygen  by 
shaking  with  air,  will  yield  as  much  as  twenty  volumes  per  cent,  of 
oxygen  to  a  Torricellian  vacuum,  the  oxygen  cannot  be  in  simple 
solution,  but  must  be  in  some  form  of  combination  with  some  of  the 
constituents  of  the  blood.  Of  this  oxygen,  practically  the  whole  is 
contained  in  the  red  blood-corpuscles  in  combination  with  haemo- 
globin, the  plasma  containing  no  more  than  could  be  accounted  for 
by  simple  solution. 

One  gramme  of  crystallised  haemoglobin  can  absorb  about  1-4  c.c. 
of  oxygen  {v.  p.  929).  If  a  solution  of  oxyhaemoglobin  be  subjected 
in  an  air-pump  to  gradually  diminishing  pressure  at  the  temperature  of 
the  body,  very  Httle  oxygen  is  given  off  until  the  partial  pressure  of  the 
oxygen  is  diminished  to  about  30  mm.  Hg.  (Fig.  494).  At  this  point  a 
large  evolution  of  gas  begins,  and  continues  at  falling  pressure  until  at 
0  mm.  pressure  all  the  oxyhaemoglobin  is  dissociated  and  converted 
into  haemoglobin.  The  same  observation  may  be  made  in  a  reverse 
direction.  If  a  solution  of  reduced  haemoglobin  be  exposed  to  gradually 
increasing  pressures  of  oxygen,  it  will  be  found  that  the  greatest 
absorption  takes  place  between  0  and  30  mm.  Hg.  After  this  point 
the  oxygen  is  more  slowly  absorbed  up  to  the  point  of  complete 
saturation. 

Since  there  is  no  direct  proportion  between  the  partial  pressure 
of  the  oxygen  and  the  amount  absorbed,  it  is  evident  that  the  oxygen 
C0nibilieS-AV4tk-hirinin(r1^f])ii»  fn  fnrni  in  iiiin<-n4T4Tr-Hipniirfl.l  rompAund. 
and  that  this  is  not  a  mere  ^estioiuif_solution.  This  is  further  proved 
by  the  fact  tliat  we"ca,n  displace  the  oxygen  (Og)  from  the  oxyhaemo- 
globin by  equivalent  amounts  of  CO  or  NO.  Hjcmogh)bin  is  also  sup- 
posed to  form  an  unstable  combination  with  carbon  dioxide,  since  it 
takes  up  much  more  of  this  gas  than  the  corresponding  bulk  of  water 


1182  THYSIOLOGY 

or  salt  solution  would  do.  Although  carbon  dioxide  conabines  with 
haemoglobin,  it  does  not  displace  oxygen  from  the  oxyhtemoglobin 
molecule.  Thus  we  may  have  hsemogiobin  saturated  at  the  same  time 
with  oxygen  and  with  carbon  dioxide.  The  presence  of  carbon  dioxide 
does,  however,  alter  the  ease  with  which  oxyhaemoglobin  dissociates. 

The  relation  between  the  partial  pressure  of  oxygen  and  the 
amount  of  oxyhsemoglobin  formed  under  varying  conditions  can  be 
investigated  in  the  following  way  (Barcroft)  : 

A  large  glass  globe  with  a  stop-cock  at  one  or  both  ends  (F'g.  493)  is  filled  with  a 
gaseous  mixture  of  kno%vn  composition  containfiig  oxygen.  Into  it  are  introduced 
2  or  3  c.c.  of  blood  or  of  haemoglobin  solution.     It  is  then  tightly  stoppered  and 


Fig.  493.     Barcroft's  apparatus  for  deterniining  the  curve  of  absorption  of 
oxygen  by  haemoglobin. 

immersed  in  a  horizontal  position  in  a  pail  of  water  kept  at  a  constant  temperatiire. 
In  the  pail  it  is  suspended  between  its  two  ends,  so  that  it  can  be  slowly  revolved 
by  means  of  a  piece  of  string  passing  round  its  neck.  In  this  way  the  blood 
is  continually  spread  in  a  thin  layer  over  the  sides  of  the  vessel.  At  the  end  of 
a  quarter  to  half  an  hour  it  will  have  attained  equilibrium  with  the  gaseous 
mixture.  It  is  then  turned  into  an  erect  position  so  that  the  fluid  can  run  down 
into  the  neck  closed  by  a  stop-cock,  whence  1  c.c.  may  be  drawn  off  for  analj^sis 
in  a  Barcroft  apparatus.  A  fm-ther  portion  of  the  same  blood  may  be  shaken 
up  with  air  so  as  to  satiu-ate  it  completely,  and  the  saturation  of  the  two  samples 
may  be  compared  in  the  differential  gas  apparatus. 

Barcroft  has  shown  that  the  dissociation  curve  of  haemoglobin  is 
largely  altered  by  slight  variations  in  the  fluid  in  which  the  haemo- 
globin is  dissolved.  The  most  important  of  these  conditions  are  (1)  the 
sahne  content  of  the  fluid,  (2)  the  reaction  of  the  fluid.  Under  this 
latter  heading  must  be  classed  the  amount  of  carbon  dioxide  present, 
since  its  action  on  the  dissociation  curve  is  similar  to  that  produced 
by  the  presence  of  weak  acids  such  as  lactic  acid.  The  influence  of 
dissolved  sahs  on  the  dissociation  curve  is  shown  in  Fig.  494. 

It  is  interesting  to  note  that  the  differences  between  the  dissocia- 
tion curve  of  blood  and  of  haemoglobin  solution,  as  well  as  between 


THE  CHEMISTRY  OF  RESPIRATION  1183 

bloods  of  different  animals,  have  been  shown  by  Barcroft  and  Caniis  to 
be  dependent  on  the  different  saline  content  of  the  solution  in  the 
various  cases.  Thus  human  haemo<:flobin  solution,  with  a  concentra- 
tion of  salts  similar  to  that  of  dogs'  blood,  gives  the  same  dissociation 
curve  as  normal  dogs'  blood- 
More  important  is  the  effect  of  reaction,  since,  as  we  shall  see,  it  is 
the  reaction  of  the  blood,  controlled  especially  by  carbon  dioxide 


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Fig.  494.     Dissociation  curve  of  haemoglobin  in  varions  solvents. 
I,  in  0-9  per  cent.  KCl ;  II,  in  0-7  per  cent.  NaC'l ;  Til,  in  water. 
(Barcroft.) 

tension,  that  determines  the  activity  of  the  respiratory  centres.  In 
Fig.  495  is  represented  the  influence  of  varying  tensions  of  carbon 
dioxide,  and  in  Fig.  496  the  effect  of  slight  additions  of  lactic  acid 
on  the  dissociation  curve.  It  will  be  seen  that  the  more  acid  the  blood. 
or  the  greater  tension  of  carbon  dioxide  it  contains,  the  more  readilv 
does  it  undergo  dissociation.  This  is  especially  marked  at  the  very 
high  tension  of  420  mm.  carbon  dioxide.  It  plays  an  important 
part  in  the  lower  tensions,  such  as  40  and  80  mm.  Hg.  carbon 
dioxide.  It  must  be  remembered  that  40  mm.  carbon  dioxide  repre- 
sents approximately  the  normal  carbon  dioxide  tension  in  the  blood. 
It  is  true  that  at  150  mm.  oxygen  |Hossuro  the  bI(»od  is  practically 
saturated   with   oxygen    whatever    (within    pliysiological    limits)   the 


1184 


PHYSIOLOGY 


pressure  of  the  carbon  dioxide.     At  lower  pressures  of  oxygen,  how- 
ever, the  pressure  of  carbon  dioxide  makes  a  considerable  difference. 


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60       9d       iOO       HO       no      130      i¥)      ^50 


Fig.  495.  Effect  of  varying  tensions  of  CO.^  on  the  dissociation  curve  of  oxyhsemo- 
globin.  The  lowest  curve  is  the  dissociation  at  a  CO.^  tension  of  420  mm.  Hg. 
from  observations  by  Barcroft.     (Bohr.) 


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Fig.  496.     Dissociation  curves  of  sheep's  blood. 

1,  normal  blood;  2,  blood  containing  0*04  per  cent,  added  lactic  acid  : 

3,  blood  containing  008  per  cent,  added  lactic  acid. 


Thus  at  an  oxygen  pressure  of  20  mm.  Hg.  the  amount  of  oxyheemo- 
globin  formed  is  67*5  per  cent,  at  a  carbon  dioxide  pressure  of  5  mm., 
whereas  at  a  pressure  oi  carbon  dioxide  of  40  mm   the  amount  of  oxy- 


THE  CHEMISTRY  OF  RESPIRATION  1185 

hajraoglobin  is  only  29-5  per  cent.  In  consequence  of  this  fact,  in  the 
tissues,  where  the  carbon  dioxide  tension  is  high,  the  oxyhemoglobin 
will  be  dissociated  with  greater  ease,  so  that  oxygen  will  be  set  free 
where  it  is  most  wanted. 

We  are  now  in  a  position  to  understand  how  the  oxygen  is  taken 
up  by  the  blood  as  it  circulates  round  the  pulmonary  alveoh.  Arterial 
blood,  such  as  that  which  fills  the  pulmonary  veins  and  the  systemic 
arteries,  is  very  nearly  [i.e.  about  90  per  cent.)  satui-ated  with  oxygen, 
and  will  only  take  up  about  2  volumes  per  cent,  more  on  shaking 
it  with  air  at  the  body  temperature.  Venous  blood  requires  8  to 
10  volumes  per  cent,  of  oxygen  to  saturate  it ;  but  we  have 
already  mentioned  that,  at  a  tension  of  30  mm.  oxygen,  the 
blood  becomes  nearly  saturated.  The  tension  of  oxygen  in  the 
alveoli  is  considerably  above  this.  In  the  trachea  the  tension  of 
oxygen  is  about  ,V  of  an  atmosphere  (since  the  air  here  contains  16 
volumes  per  cent.),  and  the  tension  in  the  alveoli  will  be  only  a  little 
lower  than  this.  If  we  take  the  oxygen  tension  in  the  alveoh  at  1  of 
an  atmosphere,*  it  will  still  be  something  over  100  mm.  Hence  the 
venous  blood  brought  to  the  alveoli  by  the  pulmonary  artery  will,  on 
there  coming  into  intimate  contact  with  the  atmosphere,  take  up 
oxygen  from  it  to  saturation,  or  to  a  point  not  far  removed  from  it. 

The  blood,  thus  laden  with  oxygen,  travels  to  the  left  side  of  the 
heart,  and  from  there  is  sent  through  the  arteries  to  all  parts  of  the 
body.  It  must  be  remembered  that  neither  in  the  lungs  nor  in 
the  tissues  does  the  haemoglobin  come  in  actual  contact  with  the  source 
of  the  oxygen,  nor  with  the  cells  which  it  is  to  supply.  In  both  cases  the 
interchange  is  effected  through  the  intermediation  of  the  plasma  and, 
in  the  tissues,  of  the  lymph  as  well.  Since  the  tissue-elements  are  con- 
stantly using  up  oxygen,  they  absorb  any  oxygen  that  is  present  in  the 
surrounding  lymph.  There  is,  in  consequence,  a  descending  scale  of 
oxygen  tensions  from  red  blood-corpuscle  through  plasma,  vessel  wall, 
lymph,  and  tissue-element.  The  cell  draws  from  the  Unnph.  and  the 
lymph  from  the  plasma,  so  that  the  oxygen  tension  in  the  plasma  sinks. 
This  has  the  same  effect  as  if  we  put  the  red  corpuscles  in  a  mercurial 
pump  and  lowered  the  pressure  of  gas.  The  immediate  result  is  an 
evolution  of  oxygen,  which  is  taken  up  by  the  plasma,  to  be  in  turn 
passed  on  to  the  lymph  and  the  tissue-cell. 

Under  normal  circumstances  a  blood-corpuscle  never  stays  long 
enough  in  the  proximity  of  the  tissues  to  lose  its  whole  store  of  oxygen. 
If,  however,  the  further  supply  of  oxygen  to  the  blood  be  prevented, 
as  in  asphyxia,  the  last  traces  of  oxygen  disappear  from  the  blood. 
The  enormous  avidity  of  the  tissues  for    oxygen  is  shown  by  the 

*  The  oxygen  tension  in  the  alveoli  has  been  reckoned  at  about  12-6  per  cent. 
to  13-5  per  cent,  of  an  atmosphere. 

75 


1186  PHYSIOLOGY 

following  experiment  (Ehrlich).  |  If  a  saturated  solution  of  methylene 
blue  be  injected  into  the  circulation  of  a  living  animal  and  the  animal 
be  killed  ten  minutes  later,  it  is  found  on  first  opening  the  body  that 
most  of  the  organs  present  their  natural  colour,  although  the  blood 
is  a  dark  blue  colour.  On  exposure  to  the  atmosphere  all  the  organs 
acquire  a  vivid  blue  colour.  The  avidity  of  the  tissues  for  oxygen  has 
been  so  great  that  they  have  been  able  to  decompose  the  methylene- 
blue  molecule,  with  the  formation  of  a  colourless  reduction-product, 
which  on  exposure  to  the  air  undergoes  oxidation  again  and  re-forms 
methylene  blue.  If  the  tissues  are  able  to  effect  the  reduction  of  a 
comparatively  stable  body  like  methylene  blue,  it  is  easy  to  understand 
their  power  of  reducing  oxyhsemoglobin,  which  is  so  unstable  that  it 
is  decomposed  by  simple  physical  means  such  as  exposure  to  a  vacuum  ^y 

It  was  long  debated  whether  the  chief  processes  of  oxidation 
took  place  in  the  blood  or  in  the  tissues.  Our  experiences  with  muscle 
would  alone  serve  to  couAnnce  us  that,  in  some  tissues  at  any  rate,  pro- 
cesses of  oxidation  take  place,  and  the  methylene-blue  experiment 
shows  that  these  processes  of  oxidation  are  intense  in  all  the  chief 
organs  of  the  body.  It  has  been  found  moreover  that  it  is  possible  to 
keep  a  frog  alive  after  substituting  normal  saline  solution  for  his  blood, 
if  he  be  placed  in  absolutely  pure  oxygen,  and  that  in  this  case  indeed 
the  metabolism  of  the  animal  goes  on  as  actively  as  before.  As  the 
frog  has  no  blood,  it  is  evident  that  its  metabolic  processes,  consisting  of 
the  taking  up  of  oxygen  and  the  giving  out  of  carbon  dioxide,  must 
have  their  seat  in  the  tissues. 

As  a  result  of  the  oxidative  changes  in  the  tissues  carbon  dioxide 
is  produced,  and  the  tension  of  this  gas  in  the  tissues  therefore  rises.  As 
Barcroft  has  pointed  out,  in  cold-blooded  animals  the  dissociation  of  oxy- 
haemoglobin  with  the  setting  free  of  oxygen  must  be  largely  conditioned 
by  the  rise  of  carbon  dioxide  tension  in  the  tissues,  since  at  the  normal 
temperature  of  these  animals  the  evolution  of  oxygen  from  haemoglobin 
is  extremely  slow.  The  alteration  in  reaction  of  the  blood  caused  by 
a  rise  in  COg  tension  or  by  the  presence  of  small  amounts  of  lactic  acid, 
markedly  quickens  the  rate  at  which  oxyhsemoglobin  gives  up  its 
oxygen,  as  is  shown  in  Fig.  497.  The  carbon  dioxide  tension  in  the 
tissues  may  be  approximately  measured  by  taking  the  tension  of  this 
gas  in  fluids  such  as  the  bile  or  urine.  Here  it  may  amount  to  8  or  10 
per  cent,  of  an  atmosphere,  and  since  the  carbon  dioxide  in  venous 
blood  is  rarely  above  6  per  cent,  of  an  atmosphere,  there  is  a  descending 
scale  of  tensions  from  tissue  to  blood,  just  as  there  is  an  ascending  scale 
in  the  case  of  oxygen.  This  gas  therefore  passes  from  the  tissues  through 
the  lymph  into  the  blood  by  a  simple  process  of  diffusion. 

The  carbon  dioxide  carried  by  the  blood  is,  like  the  oxygen,  chiefly 
m  a  state  of  chemical  combination.     From  dogs'  venous  blood  we 


THE  CHEMISTRY  OF  RESPIRATION 


1187 


may  obtain  by  means  of  the  pump  about  50  c.c.  of  carbon  dioxide 
per  100  c.c.  blood.  Water  at  the  temperature  of  the  body,  if  shaken 
up  with  an  atmosphere  of  carbon  d'loxide  at  a  pressure  of  760  mm.  Hg., 
would  take  up  about  50  p.c.  of  the  gas,  and  the  plasma  as  a  mere  solvent 
would  take  up  slightly  less.  The  tension  of  carbon  dioxide  in  the 
blood  is,  however,  much  less  than  1  atmosphere.  Shaken  up  with 
pure  carbon  dioxide  at  a  pressure  of  1  atmosphere,  the  blood  would 
take  up  as  much  as  150  per  cent.  If  we  determine  the  tension  of  the 
carbon  dioxide  in  the  blood  bv  one  of  the  methods  to  be  described 


Normdl 


12-5 

Fig.  497.  Curves  showing  the  rate  at  whieh  oxyha?moglobin  is  reduced  on 
bubbling  through  a  gas  free  from  oxygen,  and  the  effect  on  the  rate  of  the 
presence  of  CO.,  and  of  lactic  acid.  Ordinates  —  percentage  saturation  of 
Qxyhaemoglobin.     AbscLssae  =  time  in  minutes.     (Mathison.) 

later,  we  find  that  in  venous  blood  this  gas  is  at  a  pressure  of  only  about 
5  to  6  per  cent,  of  an  atmosphere  (about  40  mm.  Hg.).  Taking  the 
pressure  of  the  carbon  dioxide  as  ^  of  an  atmosphere,  and 
knowing  that  at  a  pressure  of  1  atmosphere  the  blood  might  dis- 
solve 50  volumes  per  cent.,  it  is  evident  that  at  ^  of  an  atmosphere 
the  blood  would  only  dissolve  f^  volumes  per  cent.,  i.e.  about  '1\ 
volumes.  All  the  rest  of  the  carbon  dioxide  in  the  blood  must  there- 
fore be  in  combination  (cp.  Fig.  498). 

The  carbon  dioxide  is  contained  chiefly  in  the  plasma,  though  a 
certain  amount  is  also  in  combination  in  the  corpuscles.  It  is  evident 
that  part  of  the  carbon  dioxide  at  any  rate  must  be  in  combination  with 


1188 


PHYSIOLOGY 


some  constituent  common  to  both  plasma  and  corpuscles,  and  it  is 
natural  to  think  first  of  the  alkalies  of  the  blood.  When  blood-plasma 
is  calcined,  the  ash  is  found  to  be  distinctly  alkaline  and  to  contain  an 
amount  of  sodirmi  greater  than  is  necessary  to  combine  with  the  other 
acid  radicals,  e.g.  CI,  SO 4,  and  PO4,  and  this  excess  becomes  greater  if 
we  consider  that  a  great  part  of  the  PO4  and  SO 4  is  derived  from  the 
oxidation  of  the  sulphur  and  phosphorus  present  in  organic  combina- 
tion in  the  plasma.  We  may  therefore  conclude  that  a  considerable 
part  at  any  rate  of  the  carbon  dioxide  exists  in  the  plasma  as  sodium 
carbonate  or  sodium  bicarbonate.     In  the  same  way  a  certain  pro- 


^ 

^ 

^ 

^ 

0 

n 

,  ^ 

^ 

^ 

p 

0 

^ 

^^ 

/ 

/ 

/ 

> 

/ 

/ 

/ 

0        10     20     30     40     50     60      70     80     90    100  110   120    130 

Fig.  498.     Curve  of  CO2  tension  in  blood. 

Ordinates  =  c.c.  COo  in  100  c.c.  blood  ;  abscissae  =  tension  of  CO.j  in  mm.  Hg. ; 

o  as  determined  by  Jaquet ;    x  as  determined  by  Bohr. 

portion  of  the  carbon  dioxide  which  is  held  by  the  corpuscles  is  probably 
in  combination  with  sodium.  Haemoglobin  also  has  the  power  of 
combining  with  carbon  dioxide,  and  unstable  compounds  may  be  formed 
between  carbon  dioxide  and  the  proteins  of  the  plasma  itself.  Accord- 
ing to  Loewy  one  hundred  cubic  centimetres  of  arterial  blood  from  the 
dog  would  yield  normally  about  40  c.c.  of  carbon  dioxide.  These  40  c.c. 
would  be  divided  as  follows  : 

In  simple  solution  in  the  plasma  and  corpuscles 

,.        ,  .      1        .     r(o)  in  corpuscles         .  .  .       6-8 "i 

As  sodium  bicarbonate     ;;,;  •      ,  i  o  a 

\\b)  m  plasma    ....     12-0  / 

In  organic  combination  with  haemoglobin  in  corpuscles     .       7-5) 

In  organic  combination  with  proteins  of  the  plasma  .     11 -8  J 

It  will  be  noted  that  although  we  are  dealing  here  with  arterial 
blood,  in  which  the  tension  of  carbon  dioxide  is  comparatively  low, 


1-9  c.c. 
18-8   c.c. 

19-3   c.c. 


THE  CHEMISTRY  OF  RESPIRATION  1189 

the  carbon  dioxide  is  stated  to  be  in  combination  as  bicarbonate. 
This  is  on  account  of  the  fact  that  in  no  case  is  the  alkalinity  of  the 
blood  equal  to  that  of  a  solution  of  sodium  carbonate.  On  the  other 
hand,  if  we  expose  blood  to  a  vacuum  the  whole  of  the  carbon  dioxide 
is  given  ofE.  If  sodium  bicarbonate  be  exposed  to  a  vacuum,  only 
half  of  the  carbon  dioxide  is  evolved,  sodium  carbonate  itself  not 
undergoing  any  decomposition  in  vacuo.  If  we  attempt  to  extract  the 
carbon  dioxide  from  blood-serum  or  blood-plasma,  we  may  obtain 
nearly  all  the  carbon  dioxide  present,  the  last  5  per  cent.,  however, 
requiring  the  addition  of  a  weak  acid  such  as  oxalic  or  phosphoric  acid 
in  order  that  it  may  be  given  off.  How  are  we  to  explain  the  difference 
between  the  behaviour  of  blood  and  the  behaviour  of  a  solution  of 
sodium  bicarbonate  ? 

We  may  artificially  make  a  fluid  which  behaves  to  carbon  dioxide 
in  the  same  way  as  blood,  by  mixing  together  sodium  carbonate 
and  sodium  hydrogen  phosphate  Na2HP04.  From  such  a  mixture 
the  whole  of  the  carbon  dioxide  may  be  given  oflt  when  exposed  to  a 
vacuum.  On  the  other  hand,  a  large  amount  of  carbon  dioxide  will 
be  taken  up  with  a  very  small  difference  in  tension  of  the  gases.  The 
behaviour  of  the  mixture  is  due  to,  an  interaction  which  occurs  between 
the  acid  radicals  PO4  and  CO  3.  When  the  mixture  is  exposed  to 
a  vacuum  any  sodium  bicarbonate  present  will  undergo  dissociation, 
carbon  dioxide  being  given  off  and  the  carbonate  NagCOg  formed. 

This  then  reacts  with  the  sodium  phosphate  in  the  following  way  : 

2NaH,P04  +  Na^COa  =  2Na,HP04  +  CO,  +  HgO. 

In  this  way  the  whole  of  the  sodium  enters  into  combination  with  the 
PO4  radical  and  the  carbon  dioxide  previously  combined  is  given  off. 
On  exposing  the  mixture  to  an  atmosphere  containing  carbon  dioxide, 
the  reverse  change  takes  place,  and  we  get  once  again  sodium  hydrogen 
phosphate  and  sodium  carbonate,  and  finally  sodium  bicarbonate. 
It  was  formerly  thought  that  in  the  blood-plasma  phosphates  were  an 
important  factor  in  the  evolution  of  the  carbon  dioxide.  Blood- 
plasma,  however,  contains  the  merest  trace  of  phosphates,  and  the 
role  of  a  weak  acid  competing  with  the  carbon  dioxide  for  the  sodium 
is  played  chiefly  by  the  proteins  of  the  plasma.  We  can  in  fact,  by 
adding  proteins  to  a  solution  of  sodium  carbonate  and  exposing  the 
mixture  to  a  vacuum,  obtain  the  evolution  of  practically  all  the  carbon 
dioxide  previously  in  combination  with  the  sodium.  In  the  cor- 
puscles both  ha)moglobin  and  proteins  play  the  part  of  a  weak  acid. 
When  plasma  is  exposed  to  a  vacuum  it  is  necessary,  as  we  have  seen, 
to  add  a  little  acid  in  order  to  obtain  the  last  traces  of  carbon  dioxide 
from  the  fluid.  Instead  of  adding  a  weak  acid,  ha)moglobin  or  red 
blood-corpuscles   may   be   employed.     In   the   latter   case   it   seems 


1190 


PHYSIOLOGY 


probable  that  the  action  on  the  carbonates  of  the  plasma  is  due  not  so 
much  to  the  haemoglobin  as  to  an  interchange  of  acid  radicals  between 
the  corpuscles  and  the  plasma.  If  carbon  dioxide  be  passed  into 
defibrinated  blood  the  alkalinity  of  the  plasma  increases  while  the 
chlorides  diminish,  and  it  is  probably  the  reverse  interchange  of 
radicals  between  corpuscles  and  plasma  which  is  responsible  for  the 
evolution  of  carbon  dioxide  on  the  addition  of  corpuscles  to  plasma 
in  vacuo. 

THE  ALKALINITY  OF  BLOOD.  Blood-plasma  is  generally  de- 
scribed as  slightly  alkaline,  and  its  alkalinity  is  measured  in  terms 
of  deci-  or  centinormal  acid.  The  term  alkalinity  is  relative.  Caustic 
alkali  owes  its  alkalinity  to  the  presence  of  OH  ions.  The  neutrality 
of  distilled  water  is  due  to  the  presence  of  practically  equal  amounts  of 
H  and  OH  ions  in  the  fluid.  We  may  measure  the  concentration  of 
H  or  OH  ions  in  a  fluid  electrically.*  If  this  electrical  method  be 
applied  to  blood  or  blood-plasma  it  reveals  either  of  these  fluids 
as  practically  neutral,  i.e.  there  is  little  or  no  greater  concentration  of 

*  By  the  use  of  different  indicators  we  may  arrive  at  some  conclusion  as  to 
the  approximate  concentration  of  hydrogen  ions  in  any  given  liquid.  In  the 
following  Table  are  set  out,  from  a  papei;  by  Eoaf,  the  colours  of  a  number  of 
different  indicators,  and  the  degree  of  acidity  which  is  sufficient  to  change  their 
colours : 


Indicator 

Acid  colour 

Transitional 
colour 

Alkaline  colour 

Hydrogen  ion  concentra- 
tion at  which  colour 
change  begins 

Dimethyl - 
amido- 
azobenzol 

-      Red 

Orange 

Yellow 

1  X  10=* 

Congo  red 

Blue      1 

Purple  and 
bro^vn 

1      Red 

1  X  10-" 

Vesuvin 
brown 

/■     Brown 

— 

Yellow 

1   X  10-" 

Gallein 

Colourless 

Pink 

Red 

1  X  lO-* 

Na  alizarine 
sulphonate 

1     Yellow 

Orange 

Red 

1  X  10" 

Lacmoid 

Red 

Purple 

Blue 

1  X  10"  -  1  X  10-« 

Rosolic  acid 

Yellow 

Orange 

Red 

1  X  10-'^ 

Litmus 

Red 

Purple 

Blue 

1  X  10-^  -  1  X  lO** 

Neutral  red 

Red 

Orange 

Yellow 

1  X  10-« 

Alizarine 

YeUow 

Orange 

Red 

1  X  10  « 

Phenol - 
phthalein 

-  Colourless 

Pink 

Red 

1  X  10-» 

It  should  be  remembered  that  in  distilled  water  of  the 
the  concentration  of  H  and  OH  ions  respectively  is  about 


highest  state  of  purity 
1  X  10  '. 


THE  CHEMISTRY  OF  RESPIRATION  1191 

H  or  OH  ions  in  blood  than  in  distilled  water.  The  reaction  of  blood  as 
normally  taken  depends  as  a  matter  of  fact  on  the  indicator  which  is 
used.  Thus  blood-plasma  is  acid  to  phenolphthalein,  but  alkaline  to 
litmus.  On  the  other  hand,  the  carbon  dioxide  and  proteins  in  combi- 
nation with  the  sodium  may  be  easily  replaced  by  stronger  acid  radicals, 
and  if  the  carbon  dioxide  be  allowed  to  escape,  very  little  change  in  the 
reaction,  i.e.  in  the  concentration  of  H  or  OH  ions  respectively,  will  be 
produced.  We  may  thus  speak  of  blood-plasma  as  actually  neutral, 
though  potentially  alkahne  in  that  it  can  neutralise  a  considerable 
amount  of  acid.  This  potential  alkalinity  is  more  important  than  the 
actual  alkalinity,  since  on  it  depends  the  power  possessed  by  the  blood 
of  carrying  carbon  dioxide  from  the  tissues  to  the  lungs.  By  adding  a 
fixed  acid  to  the  blood  we  may  use  up  this  potential  alkalinity  and 
finally  arrive  at  a  point  at  which  each  addition  of  acid  makes  a  propor- 
tionate increase  in  the  actual  acidity,  i.e.  in  the  concentration  of  H  ions. 
From  this  time  forward,  however,  the  plasma  has  lost  its  power  of 
binding  carbon  dioxide  and  can  carry  this  gas  only  in  simple  solution. 
On  exposure  of  such  plasma  to  carbon  dioxide  the  tension  of  the  gas 
rapidly  rises  in  the  fluid.which  becomes  saturated  when  only  a  relatively 
small  amount  of  gas  has  entered  into  the  fluid.  Any  diminution  of  the 
so-called  alkalinity  of  the  blood  or  blood-plasma  will  seriously  impair 
the  function  of  the  blood  in  respiration-  An  example  of  such  a 
condition  is  the  acidosis  which  occurs  in  diabetes,  or  in  any  other  form 
of  carbohydrate  starvation. 

EXCHANGE  OF  GASES  IN  THE  LUNGS 

A  fluid  gives  ofi  gas  to  or  takes  up  gas  from  any  other  medium 
with  which  it  is  in  contact  according  to  the  relative  pressures  of  the 
gas.  The  question  arises  whether  the  physical  conditions  in  the  lungs 
are  such  as  to  account  for  the  absorption  of  oxygen  and  the  evolution 
of  carbon  dioxide  by  the  blood  in  its  passage  through  these  organs.  In 
order  to  answer  this  question  we  must  know  the  partial  pressures  or 
tensions  of  oxygen  and  of  carbon  dioxide  in  the  alveolar  air,  in  the 
venous  blood  coming  to  the  lungs,  and  in  the  arterial  blood  leaving 
the  lungs.  In  the  alveoli  the  pressures  are  given  by  the  analysis  of 
alveolar  air.  The  determination  of  the  gaseous  tensions  in  the  blood 
presents,  however,  considerable  difficulty.  It  is  necessary  to  bring 
the  blood  in  contact  with  gaseous  mixtures  containing  various  pro- 
portions of  the  gas  whose  tension  in  the  blood  it  is  desired  to  measure. 
By  making  various  experiments  a  gaseous  mixture  will  be  found  with 
which  the  blood  is  in  equihbrium.  If  we  know  beforehand  the  amount 
of  gas  in  this  mixture,  we  know  its  tension  and  therefore  the  tension 
of  the  gas  in  the  liquid. 


1192 


PHYSIOLOGY 


Pfliiger's  aerotonometer  (Fig.  499)  consists  of  two  glass  tubes,  R  and  E, 
contained  in  a  vessel  filled  with  water  at  the  temperature  of  the  body.  The 
upper  ends  of  the  tubes  are  connected  by  the  tube  a  with  the  artery  or  vein 
in  which  it  is  desired  to  estimate  the  tension  of  the  blood-gases.  If,  for  instance, 
we  wish  to  determine  the  tension  of  CO2  in  venous  blood,  where  we  expect  the 
tension  to  amount  to  about  4  per  cent,  of  an  atmosphere,  one  tube  R  is  filled 
with  a  gaseous  mixture  containing  3  per  cent.  CO2,  and  the  other  tube  R  with  a 
mixtiu-e  containing  5  per  cent.  CO2.  a  is  now  connected  with  the  distal  end  of 
the  jugular  vein,  or  with  the  central  end  of  the  carotid  artery,  and  blood  is 
allowed  to  flow  in  a  thin  stream  do%vn  the  walls  of  the  tubes  r  and  R,  thus 
presenting  a  large  surface  to  the   contained  gases.      The  blood  collects  in  the 


Fig.  499.     Pfliiger's  aerotonometer. 


lower  narrower  portions  of  the  tubes,  and  runs  out  into  the  vessels  h,  b,  whence 
after  defibrination  it  is  returned  at  intervals  into  the  vems  of  the  animal. 

Bohr's  aerotonometer  was  built  on  the  plan  of  the  Stromaiche  devised  by 
Ludwig,  and  could  be  inserted  in  the  com-se  either  of  an  artery  or  of  a  vein.  In 
using  this  instrument  it  is  advisable  to  inject  some  substance  like  peptone  or, 
better,  hirudin,  in  order  to  prevent  coagulation  of  the  blood. 

In  all  these  instruments,  however,  the  main  difficulty  is  in  obtain- 
ing a  sufficient  surface  of  the  blood  exposed  to  the  gaseous  mixture. 
The  interchange  of  gases  is  thus  very  slow,  and  it  is  difficult  to  be  certain 
at  any  time  that  the  blood  and  the  gas  with  which  it  is  in  contact  are 
really  in  equilibrium.  Krogh  therefore  adopted  an  ingenious  device 
of  limiting  the  volume  of  air  to  a  small  bubble,  the  superficial  area  of 
which  is  large  in  proportion  to  its  bulk.  This  bubble,  after  it  has  been 
in  a  stream  of  blood  for  some  minutes,  is  transferred  to  a  special 
capillary  tube  in  which  its  analysis  can  be  carried  out  with  a  fair  degree 
of  accuracy. 


THE  CHEMISTRY  OF  RESPIRATION 


1193 


The  performance  of  a  tonometer  may  be  expressed  by  the  ratio  of  the  sxiriace 
of  blood  exposed  to  the  volume  of  the  air  used.  The  '  specific  surface  '  of  an  aero- 
tonometer  is  represented  by   ^-^  ""  ^^'  ^'^'.     The  specific  surface  of  Pfliiger's 

volume  m  c.c. 
instrument  is  only  3-3  and  of  Bolir's  only  5-2.     In  Krogh's  microtonometer  the 
absolute  volume  of  air  employed  is  reduced  to  a  bubble  of  about  2  mm.  in  diameter, 
having  a  volume  of  -004  c.c.  and  a  surfaceof  0-125  sq.  cm.,  so  that  its  specific  surface 
is  30.     In  such  a  bubble  the  equalisation  of  the  tensions  takes  place  ^ath  an  extreme 

B 


^^m 


Fig.  500.  a,  Krogh's  microtonometer.  b,  upper  part  of  microtonometer 
showing  capillary  tube  into  which  the  bubble  is  returned  for  measure- 
ment and  analysis. 


rapidity  and  only  a  minute  quantity  of  fluid  is  necessary.  The  microtonometer 
consists  of  the  tonometer  proper  and  the  apparatus  for  the  microanalj'sis  of  the  gas 
bubble.  In  the  latter  the  measurement  of  the  gas  bubble  is  carried  out  in  a 
capillary  tube,  the  absorption  of  carbon  dioxide  and  of  oxygen  being  carried  out 
in  the  usual  way  with  potash  and  with  p^Togallic  acid.  The  tonometer  is  repre- 
sented in  Fig.  500.  It  is  kept  in  a  small  water-bath  at  the  temperature  of  the 
blood  to  be  examined.  The  tonometer  is  filled  with  saline  solution  and  contains 
the  gas  bubble  2,  which  can  be  di'awii  up  by  means  of  the  screw  4  into  the  narrow 
graduated  tube  3,  where  its  volume  is  measvired.  The  blood  from  the  artery  or 
vein,  the  tension  of  the  gas  in  which  wo  wish  to  examine,  passes  by  a  caiuiula 
through  the  tube  1,  and  enters  tlie  tonometer  as  a  fine  jet.  It  forces  its  way 
up  above  the  gas  bubble,  which  is  pressed  a  little  down  by  the  current,  and 
ki^pt  oscillatuig  with  great  rapidity.     Fi'om  the  tonometer  the  blood  flows  back 


1194 


PHYSIOLOGY 


through  the  tube  7  and  is  collected  in  a  vessel  where  it  can  be  measured  and 
afterwards  drawn  off  and  reinjected  into  the  animal  if  necessary.  Since  the 
total  pressirre  of  the  gases  in  the  blood  is  nearly  always  negative,  it  is  necessary 
to  keep  the  pressm'e  in  the  tonometer  also  negative.  This  is  accomplished  by 
means  of  a  mercm-y  valve  and  can  be  regidated  to  any  desired  pressure. 

During  the  course  of  a  tonometric  experiment  the  volume  of  the  gas  bubble 
is  measured  from  time  to  time  by  drawing  it  up  into  the  graduated  tube,  and  the 
pressure  is  regulated  until  the  volume  of  the  bubble  remains  constant.  After 
five  minutes  gaseous  equilibrium  will  have  been  established  between  the  gas 
bubble  and  the  surrounduig  blood,  and  it  is  only  necessary  then  to  draw  it  up 
into  the  graduated  tube  and  analyse  it  in  order  to  determine  the  tension  of  the 
gas  in  the  blood.  Clotting  of  the  blood  is  prevented  by  the  injection  of 
hirudin. 

In  the  experiments  the  tension  of  the  air  in  the  alveoli  of  the 
animal's  lungs  or  in  the  bifurcation  of  the  trachea  was  determined 


Fig.  501.     Tensions  of  O.,  and  COg  in  alveoli  compared  with  those  in  arterial 

blood  of  rabbit. 
The  dotted  lines  represent  the  tensions  in  the  alveolar  air,  the  uninter- 
rupted lines  the  tensions  of  the  gases  in  the  arterial  blood.     (Krogh.) 


by  taking  samples  of  the  air.  The  results  of  the  experiments  show 
that  the  tension  of  the  gases  in  arterial  blood  follows  closely  the  tension 
of  the  corresponding  gases  in  the  alveolar  air.  The  tension  of  carbon 
dioxide  in  arterial  blood  is  either  identical  with  or  very  slightly  above 
the  tension  of  the  gas  in  the  alveolar  air.  The  oxygen  tension  of  the 
blood  is  always  lower  than  the  alveolar  oxygen  tension,  and  the 
difference  is  generally  1  to  2 — even  3  to  4 — per  cent,  of  an  atmosphere. 
The  results  of  a  series  of  determinations  of  the  tensions  of  the  gases 
in  the  blood  and  alveolar  air  respectively  are  given  in  Fig.  501.  In 
Pig.  502  A  and  b  (Krogh)  the  composition  of  the  alveolar  air  was 
artificially  altered  by  increasing  the  percentage  of  carbon  dioxide 
and  of  oxygen  respectively.  It  will  be  seen  in  each  case  that 
there  was  a  corresponding  alteration  of  the  tension  in  the  arterial 
blood,  the  tension  of  carbon  dioxide  being  higher  and  that  of  oxygen 
lower  in  the  blood  than  in  the  air  throughout  the  experiment.  We 
have  no  direct  determinations  of  the  tensions  of  the  gases  in  the  blood 


THE  CHEMISTRY  OF  RESPIRATION 


1195 


of  man,  though  an  approximate  valuation  of  these  tensions  can  be 
obtained  by  knowing  the  degree  to  which  the  arterial  and  venous 
blood  respectively  are  saturated  with  oxygen  or  carbon  dioxide.  An 
indirect  method  may  be  employed  to  measure  the  gaseous  tensions 
in  the  venous  blood  coming  to  the  lungs.  It  is  possible,  as  Loewy 
has  shown,  to  block  the  right  bronchus  in  man  by  introducing  a  catheter 
tlirough  the  larynx  and  trachea,  so  that  the  renewal  of  air  in  the  right 
half  of  the  lung  is  entirely  stopped  for  some  time.     A  sample  of  air 


iki 

209S 

ii-7           %    Oj 

IS 

jn  insfiirrd 

18 

•    /■' 

air 

17 

;/ 

\\ 

16 

•I 
■1 

i  • 
1  ■ 

)i 

■ij 

1^ 

> 

\\'- 

13 

ij 

\   \ 

12 

«— ' 

1 

\    v>.  _  _ . ^ 

a 

■ 

0 

o- 

O2 

4 

'^° »— — — 

,<? 

+ —       ~~^ — "^^"^....^^^ 

~~ ^ "^ 

Z 

} 

30     *0 

JB       2        10       to       i 

0      M      SO      3      fit 

2^9        30        M       JO       J        fe       to       30 


Fig.  502.     Tensions  of  gases  in  alveolar  air  and  in  arterial  blood. 

A,  during  artificial  increase  of  oxygen  tension  in  alveoli ;  b,  during  artificial 

increase  of  CO.,  tension  in  alveoli. 


in  the  blocked  lung  can  be  taken  at  any  time  by  means  of  the  catheter. 
The  interchange  of  gases  between  alveolar  air  and  blood  will  go  on 
until  the  tension  of  gases  in  the  air  is  the  same  as  that  coming  to  the 
blocked  portion  of  lung.  By  this  means  the  tension  of  the  oxygen  in 
the  venous  blood  was  found  to  be  5-3  per  cent.  =  37  mm.  Hg,  and 
that  of  the  carbon  dioxide  6  per  cent.  =  46  mm.  Hg. 

The  tensions  in  the  alveolar  air  of  man  may  be  taken  as  follows  : 


Oxygen 
Carbon  dioxide 


107  mm.  Hg. 
40      „ 


As  the  venous  blood  enters  the  lungs  there  is  thus  a  difference  of 
pressure  of  107  -  37  =  70  mm.  Hg,  which  will  tend  to  cause  a  flow 
of  oxygen  from  alveolar  air  to  blood  and  a  difference  of  46  —  40  = 
6  mm.  Hg,  tending  to  cause  a  flow  of  carbon  dioxide  from  blood  to 
alveolar  air.     Is  this  difference  sufficient  to  account  for  the  amount 


1196  PHYSIOLOGY 

of  gas  given  ofi  or  taken  up  by  tlie  blood  in  its  passage  through  the 
lungs  ?  In  a  state  of  medium  distension  the  3000  c.c.  of  air  contained 
by  the  lungs  have  been  estimated  to  occupy  seven  hundred  million 
alveoli,  each  of  which  has  a  diameter  of  0*2  mm.,  so  that  the  total 
surface  over  which  the  blood  is  exposed  to  the  alveolar  air  amounts  to 
90  square  metres.  This  is  a  minimal  figure,  since  no  account  is  taken 
in  the  calculation  of  the  augmentation  of  surface  caused  by  the  fact 
that  the  capillaries  project  into  the  lumen  of  the  alveolus,  and  by 
Hiifner  the  total  surface  exposed  is  calculated  at  140  square  metres. 
The  former  figure,  however,  amounts  to  about  1000  square  feet  and  is 
equivalent  to  the  floor-space  of  a  room  50  feet  long  by  20  feet  wide.  It  is 
important  to  reahse  that  the  blood  passmg  through  the  pulmonary 
artery  suddenly  spreads  out  into  a  layer  which  is  not  more  than  one 
blood-corpuscle  thick,  and  is  exposed  to  the  air  over  this  huge  area, 
whence  it  is  picked  up  again  and  collected  into  the  pulmonary  veins. 
Such  a  means  of  facilitating  rapid  interchange  of  gases  between  the 
blood  and  a  given  volume  of  air  we  cannot  possibly  imitate  artificially. 
The  thickness  of  the  tissue  separating  this  layer  of  air  from  the  alveolar 
air  is  on  the  average  '004  mm.  Loewy  and  Zuntz  have  directly  calcu- 
lated the  velocity  of  diffusion  of  carbon  dioxide  and  nitrous  oxide 
through  the  frog's  lung  and  have  calculated  therefrom  the  rate  at 
which  oxygen  wo  aid  diffuse  through  a  similar  layer  of  tissue,  taking 
into  accoimt  the  much  greater  solubihty  of  carbon  dioxide  as  compared 
with  oxygen.  They  calculate  that  under  a  constant  difference  of 
pressure  of  35  mm.  Hg,  6"7  c.c.  of  oxygen  would  pass  in  a  minute 
through  each  square  centimetre  of  the  alveolar  wall.  Through  the 
whole  surface  of  the  lung  this  would  amount  to  an  absorption  of  6083  c.c. 
oxygen.  The  oxygen  actually  absorbed  by  a  man  at  rest  amounts  to 
about  300  c.c.  per  minute,  so  that  the  physical  conditions  allow  an 
ample  margin  for  any  increase  in  the  consumption  of  oxygen  ;  in  fact, 
a  difference  of  pressure  of  a  couple  of  milUmetres  would  suffice  to  cause 
a  passage  of  the  250  c.c.  per  minute  which  is  required  by  the  resting 
man.  In  the  same  way  it  is  easy  to  account  for  the  passage  of  carbon 
dioxide  in  the  reverse  direction.  This  gas  diffuses  about  twenty-five 
times  as  rapidly  as  oxygen,  so  that  a  difference  of  pressure  between 
the  blood  and  the  alveolar  air  amounting  to  only  "03  mm.  Hg  would 
suffice  to  cause  a  passage  outwards  of  the  250  c.c.  normally  expired  per 
minute. 

It  is  evident  that  the  only  limitation  for  the  absorption  of  oxygen  is 
given  by  the  power  of  the  haemoglobin  to  combine  with  the  oxygen 
which  passes  through  the  alveolar  wall  into  the  blood-plasma. 

If  we  look  at  the  dissociation  curve  of  the  oxyhsBmoglobin  in  mamma- 
lian blood  given  on  p.  1184  we  see  that  the  amount  of  oxygen  which  can  be 
taken  up  by  haemoglobin  in  the  presence  of  the  normal  tension  of  carbon 


THE  CHEMISTRY  OF  RESPIRATION  1197 

dioxide,  ».e.40mm.Hg,  begins  to  diminish  very  rapidly  when  the  pressure 
of  the  oxygen  falls  below  50  mm.  Hg.  Thus  at  40  mm.  oxygen  pressure 
and  a  carbon  dioxide  tension  of  40  mm.,  oxyhsemoglobin  is  about  65  per 
cent,  saturated,  and  at  30  mm.  it  is  only  50  per  cent,  saturated.  Under 
normal  circumstances  the  blood  leaves  the  lungs  over  90  per  cent,  satu- 
rated with  oxygen.  If  the  saturation  falls  to  60  per  cent,  we  should 
expect  to  obtain  evidence  of  failure  of  oxygen  supply  to  the  tissues. 
According  to  Loewy  the  oxygen  tension  in  the  alveoli  can  sink  to 
between  30  and  35  mmr  Hg  before  any  signs  of  oxygen  lack  make  their 
appearance.  These  results  were  obtained  by  exposing  a  man  in  a  state 
of  complete  rest  to  reduced  pressure  in  an  air-chamber.  Under  these 
conditions  the  slightest  muscular  exertion  would  at  once  tend  to  cause 
distress  from  deficient  oxygen  supply.  The  exact  percentage  of  oxygen 
in  the  inspired  air  which  would  give  an  alveolar  oxygen  tension  oi 
30  to  35  mm.  varies  with  the  depth  of  respiration.  Thus  with  shallow 
respiratory  movements  the  pressure  may  sink  to  35  mm.  Hg  when  the 
inspired  air  contains  as  much  as  12  per  cent,  oxygen.  If  the  move- 
ments be  deeper  the  oxygen  content  of  inspired  air  may  be  reduced 
to  9  or  10  per  cent,  before  respiratory  distress  is  observed. 

The  view  that  in  the  interchange  of  gases  in  the  lungs  the  membrane  between 
the  blood  and  the  alveolar  air  plays  simply  a  passive  part  was  till  recently  by 
no  means  universally  accepted.  In  Bohr's  experiments  on  the  tension  of  oxygen 
and  carbon  dioxide  in  the  blood  as  determined  with  his  aerotonometer,  oxygen 
tensions  were  often  found  considerably  higher  in  the  blood  than  in  the  air  of  the 
alveoli,  and  in  the  same  way  the  carbon  dioxide  tension  of  the  blood  leaving  the 
lungs  was  found  to  be  less  than  the  carbon  dioxide  tension  of  the  alveolar  air. 
Krogh's  experiments  show  conclusively,however,that  these  results  are  not  reliable, 
and  that  the  difference  between  the  tensions  in  the  alveoli  and  in  the  blood 
respectively  is  always  such  as  to  allow  of  the  passage  by  diffusion  of  oxj'gen 
inwards  and  carbon  dioxide  outwards  from  the  blood.  Moreover,  as  Krogh 
points  out,  the  structure  of  the  pulmonary  epithelium  lends  no  support  to  the 
view  that  it  acts  as  a  secreting  membrane.  In  mammals  the  cells  are  of  two 
kinds,  viz.  small  granular  nucleated  cells  lying  in  the  interstices  of  the  capillaries, 
and  larger,  extremely  thin  structureless  plates,  without  nuclei,  covering  the 
capillaries.  In  birds,  where  the  gaseous  exchange  is  of  all  animals  the  most 
rapid  and  efficient,  the  existence  of  a  lung  epithelium  has  never  been  demon - 
8trated,and  the  capillaries  appear  to  be  almost  completely  free  and  to  be  surrounded 
with  air  on  both  sides. 

Bohr's  view  as  to  the  secretory  function  of  the  pulmonary  epithelium  was 
supported,  as  concerns  the  intake  of  oxygen,  by  Haldane.  This  observer  has 
devised  a  method  of  determining  the  oxygen  tension  of  the  blood  in  the  lungs 
founded  on  the  use  of  carbon  monoxide.  It  has  already  been  mentioned 
that  carbon  monoxide  has  the  power  of  displacing  oxygen  from  oxj'haemo- 
globin  to  form  a  much  more  stable  compoimd,  carboxyhaemoglobin.  If 
blood  be  shaken  up  with  a  mixture  of  oxygen  and  carbon  monoxide,  the 
hsemoglobin  distributes  itself  between  the  two  gases.  In  order,  however,  to 
get  an  equal  distribution,  it  is  necessary  to  take  a  very  small  percentage 
of  carbon  monoxide,  owing  to  its  greater  avidity  for  haemoglobin.  Thus,  if 
haemoglobin  solution   be   shaken  up   with   air  containing  -07  per  cent,  of  CO, 


1198  PHYSIOLOGY 

the  result  is  a  mixture  of  equal  parts  of  oxy-  and  carboxyhsemoglobin.     The 

21 

affinity  of  CO  for  haemoglobin  would  thus  appear  to  be  about  —  =  300  times 

the  affinity  of  oxygen  for  haemoglobin. 

Carbon  monoxide  is  not  destroyed  in  the  body,  so  that  if  a  mixture  con- 
taining a  small  proportion  of  CO  be  breathed,  this  gas  will  be  taken  up  until 
a  certain  percentage  of  haemoglobin  is  converted  into  CO  haemoglobin  and  the 
tension  of  CO  in  the  tissues  and  fluids  of  the  body  is  equal  to  that  of  the  in- 
spired air.  The  amount  of  haemoglobin  which  is  converted  into  carboxyhaemo- 
globin  will  serve  as  a  measure  of  the  relative  tensions  of  CO  and  oxygen  in 
the  Ivmgs.  If  the  oxygen  tension  of  arterial  blood  were  the  same  as  that  of  air, 
we  should  expect  that,  with  a  given  percentage  of  CO  in  the  air  breathed,  the 
final  saturation  with  CO  of  the  blood  -vnthin  the  body  would  be  the  same  as 
the  satiu"ation  of  blood  when  shaken  outside  the  body  with  air  containing  the 
same  percentage  of  CO  as  in  the  air  breathed.  It  was  found  by  Haldane,  however, 
that  in  all  cases  the  percentage  of  CO  haemoglobin  formed  was  much  less  in  the 
body  than  outside  the  body.  Thus  in  blood  shaken  up  with  air  containing 
20-9  per  cent,  oxygen  and  -045  per  cent.  CO,  the  amoimt  of  carbon  monoxide 
formed  was  31  per  cent,  of  the  whole  haemoglobin.  When  the  same  mixture  was 
inhaled  for  three  or  four  hours  by  a  man,  the  percentage  of  CO  haemoglobin  in 
his  blood  rose  only  to  26  per  cent.,  at  which  figure  it  remained  stationary.  This 
would  correspond  to  an  oxygen  tension  of  about  25  per  cent,  of  an  atmosphere, 
whereas  we  have  already  seen  that  the  oxygen  tension  in  the  alveoli  cannot  be 
greater  than  15  per  cent.  He  therefore  concluded  that  the  epithelial  cells  of 
the  alveoli  play  an  active  part  in  the  respiratory  interchange,  taking  up  the 
oxygen  on  one  side  at  a  tension  of  15  per  cent,  and  piling  it  up  on  the  other 
until  the  pressure  in  the  blood  is  much  higher  than  that  in  the  alveolar  air. 
Theoretically  there  is  no  reason  to  deny  the  possibility  of  such  powers  to  the 
pulmonary  epithelium.  We  know  that  the  secreting  cells  of  the  kidney  take  up 
urea  from  the  blood  which  contains  only  about  -02  per  cent,  of  this  substance, 
and  excrete  it  into  the  renal  tubule,  into  a  medium  containing  about  2  per  cent.  ; 
and  if  the  data  given  by  Haldane  are  correct  we  must  ascribe  an  analogous 
function  to  the  pulmonary  epithelium.  These  data,  however,  were  obtained 
by  a  colorimetric  method  working  with  very  minute  quantities  of  blood,  and 
lacked  the  support  of  control  experiments.  As  a  result  of  fm-ther  experiments, 
Haldane  has  modified  his  position  so  far  as  to  allow  that  under  normal 
conditions  the  absorption  of  oxygen  from  the  alveolar  air  takes  place  in 
accordance  with  the  difference  of  pressure,  i.e.  by  a  process  of  diffusion.  He 
is  stiU  of  opinion  that  under  abnormal  conditions,  when  the  oxygen  tension 
in  the  alveolar  air  is  very  low,  there  is  an  active  absorption  and  transference 
of  oxygen  to  the  blood  on  the  part  of  the  pulmonary  epithelium.  Why  animals 
should  evolve  a  fvmction  which  can  only  be  brought  into  play  on  climbing 
moimtains  seems  difficult  to  understand,  and  it  does  not  seem  probable  that 
a  reinvestigation  of  the  tensions  of  oxygen  in  the  blood  under  such  conditions 
by  Krogh's  method  will  lend  any  confirmation  to  Haldane's  conclusions. 

An  analogy  has  been  drawn  between  the  processes  of  gas  interchange  in  the 
lungs  and  that  in  the  swim  bladder  of  the  fish.  Bohr  has  shown  that  the  gas 
obtained  by  puncturing  the  bladder  often  contains  a  considerable  excess  of  oxygen. 
If  the  bladder  be  punctured  and  the  fish  then  left  in  the  water,  the  gas  rapidly 
reaccumulates,  and  it  is  found  on  tapping  a  second  time  that  the  percentage  of 
oxj'gen  is  largely  increased,  and  may  amount  to  between  60  and  80  per  cent,  of 
the  total  gases.  This  reaccumulation  of  the  gases  does  not  take  place  if  both 
vagi  are  cut,  and  is  therefore  ascribed  to  a  direct  secretory  activity  on  the  part 
of  the  epithelium  lining  the  swim  bladder  under  the  influence  of  the  vagus  nerves. 


THE  CHEMISTRY  OF  RESPIRATION  1199 

Bohr,  as  the  result  of  experiments  by  himself  and  some  of  his  pupils,  is  inclined 
to  endow  the  vagus  nerves  in  the  higher  vertebrates,  including  mammals,  with 
analogous  regulatory  influence  on  the  gaseous  exchanges  in  the  lungs.  As  regards 
the  evolution  of  carbon  dioxide  the  facts  elucidated  by  Haldane  himself  would 
make  one  hesitate  in  ascribing  any  special  secretory  activnty  to  the  pulmonary 
epithelium.  We  find,  namely,  that  the  respiratory  centre  reacts  immediately  to 
the  slightest  increase  in  the  tension  of  the  carbon  dioxide  in  the  alveolar  air. 
Since  this  beha\nour  of  the  respiratory  centre  is  independent  of  any  nervous 
connections  between  the  lungs  and  the  brain,  it  seems  to  indicate,  as  indeed 
Krogh  has  found,  that  the  tension  of  the  carbon  dioxide  in  the  blood  follows 
closely  the  tension  of  the  carbon  dioxide  in  the  alveolar  air.  If  the  carbon 
dioxide  were  secreted  by  the  pulmonary  epithelium  we  should  expect  the  lungs 
to  react  to  increased  carbon  dioxide  m  the  alveoli  by  simply  increasing  their 
work  so  as  to  maintain  the  tension  of  carbon  dioxide  in  the  blood  at  a  constant 
level.  This  at  any  rate  is  the  way  in  which  the  kidney  would  behave  Under 
analogous  circumstances.  Moreover  there  is  no  likeness  between  the  thick 
typical  secreting  cells  of  the  '  red  gland,'  which  is  the  gas-secreting  part  of  the 
swim  bladder,  and  the  thin  structureless  plates  which  separate  the  capillaries  of 
the  limgs  from  the  alveolar  air. 


SECTION  III 

THE  REGULATION  OF  THE  RESPIRATORY 
MOVEMENTS 

Each  movement  of  inspiration  involves  the  co-ordinated  activity 
of  a  large  number  of  muscles.  Thus  the  diaphragm  and  the  inter- 
costal muscles  must  come  into  action  at  the  same  time,  and  the 
extent  to  which  they  contract  will  determine  the  depth  of  the  inspira- 
tion. Similarly,  they  must  cease  to  act  simultaneously  if  the  act  of 
expiration  is  to  take  place.  The  rhythm  and  extent  of  the  alternate 
contractions  and  relaxations  of  the  respiratory  muscles  are  determined, 
as  we  have  seen,  by  the  needs  of  the  organism  as  a  whole.  These 
respiratory  movements  are  regulated  so  that  the  total  ventilation  of 
the  alveoli  shall  be  sufficient  to  meet  the  gaseous  exchanges  of  the 
body.  Whether  the  organism  consumes  250  or  1000  c.c.  of  oxygen 
per  minute,  the  respiratory  movements  keep  the  composition  of  the 
gas  in  the  alveoli  at  a  practically  constant  level. 

The  muscles  involved  both  in  inspiration  and  expiration  can  only 
be  thrown  into  activity  by  the  intermediation  of  nerves.  Each  act 
of  inspiration  involves  a  discharge  along  a  number  of  nerves,  e.g. 
the  facial  to  the  muscles  moving  the  alse  nasi,  the  vagus  to  the  muscles 
of  the  larynx,  the  branches  of  the  cervicle  and  brachial  nerves  to  the 
muscles  of  the  neck,  the  phrenic  nerves  to  the  diaphragm,  and  the  dorsal 
nerves  to  the  intercostal  muscles.  The  fibres  making  up  these  nerves 
are  derived  from  nerve-cells  of  the  anterior  horn,  situated  at  various 
levels  in  the  medulla  and  spinal  cord.  In  each  act  of  inspiration  or 
expiration  the  activities  of  all  these  groups  of  cells  must  be  brought  into 
relation  among  themselves,  as  well  as  with  the  needs  of  the  organism 
for  oxygen  and  for  the  elimination  of  carbon  dioxide.  It  is  conceivable 
that  the  co-ordination  of  the  activities  of  the  various  motor  nuclei 
might  be  attained  by  the  provision  of  communicating  nerve -paths 
joining  the  centres  among  themselves,  and  by  a  sensibility  of  all  these 
centres  to  the  gaseous  contents  of  the  blood  as  well  as  to  the  influence 
of  afferent  impressions  from  the  periphery.  A  much  more  efficient 
co-ordination,  however,  would  be  effected  by  the  subjection  of  these 
motor  nuclei  to  the  action  of  some  specialised  portion  of  the  central 
nervous  system  which  would  act  as  a  receiving  centre  for  afferent 
impressions  from  the  lungs  and  surface  of  the  body,  and  would  be 

1200 


REGULATION  OF  RESPIRATORY  MOVEMENTS      1201 

endowed  with  a  special  sensibilty  to  changes  in  the  composition  of 
the  blood  circulating  through  its  vessels.  Experiment  shows  that  the 
latter  method  is  emjjloyed  in  the  organism  for  the  regulation  of 
the  respiratory  movements.  If  the  spinal  cord  be  cut  across,  below 
the  seventh  cervical  nerve-roots,  the  action  of  the  intercostal  and 
abdominal  muscles  in  respiration  ceases  permanently,  although  respira- 
tion is  still  continued  by  the  rhythmic  activity  of  the  diaphragm  and 
the  other  muscles  supplied  by  nerves  leaving  the  central  nervous 
system  above  the  point  of  section.  Division  of  the  cord  at  the  first 
or  second  cervical  nerve  abolishes  the  action  of  the  diaphragm,  though 
the  movements  of  the  muscles  suppUed  by  the  facial,  vagus,  and  spinal 
accessory  nerves  continue.  A  section  of  the  brain-stem  through 
the  mid-brain  leaves  the  respiratory  movements  unaltered,  and  the 
same  absence  of  efiect  as  concerns  these  movements  may  often  be 
obtained  when  a  section  is  carried  across  the  upper  part  of  the  medulla 
about  the  level  of  the  strice  acousticce.  We  must  conclude  from  these 
experiments  that  the  motor  nuclei  of  the  cord  are  subject  to  and 
normally  thrown  into  activity  by  impulses  originating  in  the  medulla 
oblongata  and  transmitted  therefrom  down  the  spinal  cord. 

Many  experiments  have  been  made  with  the  idea  of  locating  the 
position  of  the  medullary  respiratory  centre  more  accurately.  The 
first  experiments  on  this  point  were  made  at  the  beginning  of  last 
century  by  Legallois,  whose  observations  were  confirmed  and  extended 
by  Flourens.  These  observers  described  the  respiratory  centre  as 
limited  to  a  small  area  at  the  level  of  the  apex  of  the  calamus  scrijjto- 
rius,  which  they  designated  noBud  vital  on  account  of  the  fact  that 
destruction  of  this  area  was  at  once  fatal  by  paralysis  of  respiration. 
Later  experiments  have  shown  that  the  centre  is  not  quite  so  circum- 
scribed. In  the  first  place,  it  is  bilateral,  each  centre  presiding  more 
especially  over  the  muscles  of  the  same  side  of  the  body,  so  that 
longitudinal  section  in  the  middle  Hne  does  not  destroy  the  respiratory 
movements.  Other  observers  have  located  the  centre  in  the  situation 
of  the  solitary  bundle  ('  respiratory  bundle  of  Gierke  '),  which  is  made 
up  of  the  descending  branches  of  the  vagus  nerve  after  they  have 
entered  the  medulla,  while,  according  to  Gad,  the  respiratory  centre 
is  diffused  over  a  considerable  area  of  the  forniatio  reticularis  on  either 
side  of  the  medulla.  There  is  no  doubt  that  this  centre  is  in  close 
connection  with  the  central  terminations  of  the  vagus  nerves. 

From  the  centre  on  each  side  the  efferent  impulses  to  the  motor 
nuclei  of  the  respiratory  muscles  pass  down  in  the  deeper  portions 
of  the  lateral  columns  of  the  cord.  Hemisection  of  the  cervical  cord, 
e.g.  on  the  right  side,  causes  cessation  of  the  contractions  of  the  dia- 
phragm on  the  same  side.  There  must,  however,  be  conmiissural 
fibres  joining  the  motor  nuclei  on  the  two  sides.     If  the  right  phrenic 

76 


1202  PHYSIOLOGY 

nerve  be  divided,  after  hemisection  on  the  right  side,  the  left  half  of 
the  diaphragm  at  once  commences  to  contract  rhythmically  with  each 
respiration  (Porter).  It  is  evident  that  the  cessation  of  respiration 
after  section  of  the  cord  is  not  due  to  a  condition  of  shock  of  the  lower 
spinal  centres,  since  it  is  possible  for  impulses  to  pass  down  the  cord 
and  to  cross  over  to  the  contra-lateral  diaphragm  nucleus  immediately 
after  hemisection  of  the  cord  on  the  side  of  the  nucleus. 

THE  QUESTION  OF  SPINAL  RESPIRATORY  CENTRES.  Several  physio- 
logists, e.g.  Brown  S6quard,  Langendorff,  and  Wertheimer,  have  described 
respiratory  centres  in  the  spinal  cord.  There  is  no  doubt  that  if  the  cord  be 
cut  across  in  the  upper  cervical  region,  and  artificial  respiration  maintained 
for  some  time,  cessation  of  the  respiration  may  be  followed  by  rhythmic  con- 
tractions of  the  respiratory  muscles.  These  are  especially  marked  in  yoimg 
animals  and  if  the  activity  of  the  cord  has  been  heightened  by  the  injection  of 
small  doses  of  strychnine.  Careful  observation  of  the  movements  shows,  how- 
ever, that  they  cannot  be  spoken  of  as  respiratory,  since,  although  rhythmic, 
they  are  not  co-ordinate.  The  diaphragm  may  contract  either  simultaneously  or 
in  alternation  with  the  intercostals,  and  muscles  which  are  essentially  expiratory 
at  the  same  time  as  those  which  we  are  wont  to  regard  as  inspiratory.  These 
experiments  show  merely  that  the  motor  centres  of  the  cord  can  enter  into  rhythmic 
activity  vmder  the  iofluence  of  asphyxial  conditions.  The  movements  aflfect  the 
muscles  of  the  limbs  as  well  as  those  essentially  respiratory  in  function. 

THE  AUTOMATICITY  OF  THE  RESPIRATORY  CENTRE 
We  have  now  to  inquire  what  it  is  that  keeps  the  respiratory  centre 
in  activity.  Is  the  rhythmic  discharge  of  inspiratory  impulses  from 
the  centre  due  to  rhythmic  or  continuous  stimulation  of  afferent 
nerves,  or  is  the  centre  so  constructed  that  under  the  normal  conditions 
of  its  environment  the  metabolic  activity  of  its  constituent  parts 
tends,  hke  that  of  the  heart-cells,  to  assume  a  rhythmic  character  ? 
In  other  words,  is  the  activity  of  the  centre  reflex  or  automatic  ?  It 
has  been  found  by  Kosenthal  that  rhythmic  respiratory  movements 
are  maintained  even  after  complete  section  of  the  brain-stem  at  the 
level  of  the  superior  corpora  quadrigemina,  section  of  the  cord  at  the 
level  of  the  seventh  cervical  nerve,  and  division  of  both  vagi  and  of 
the  posterior  roots  of  all  the  cervical  spinal  nerves.  It  is  true  that 
if  the  sections  of  the  brain-stem  be  placed  as  low  as  the  strice  acousticce, 
the  respiratory  movements  are  profoundly  modified  and  give  place 
to  a  series  of  inspiratory  spasms.  We  might  argue  from  this  that  the 
centre  was  capable  of  a  very  imperfect  degree  of  automatic  action, 
but  needed  the  stimulus  of  afferent  impulses  from  the  vagi  or  from  the 
higher  parts  of  the  brain  to  render  these  actions  adequate  for  the 
respiratory  needs  of  the  organism. 

In  the  above  experiment  the  centre  cannot  be  regarded  as  free 
from  all  afferent  stimuli,  since  the  mere  closure  of  the  demarcation 
current  in  the  cut  ends  of  the  nerves  would  cause  a  certain  amount 


REGULATION  OF  RESPIRATORY  MOVEIVIENTS      1203 

of  excitation,  and  the  animal  does  not  survive  sufficiently  long  to 
allow  this  condition  to  pass  off.  Hering  has  shown  that  in  the  '  spinal 
cord  frog  '  {i.e.  one  in  which  the  brain  has  been  destroyed)  section  of 
all  the  posterior  roots  absolutely  destroys  all  mobility,  the  injection 
of  strychnine  being  without  effect.  A  typical  spasm,  however,  can 
be  at  once  produced  by  exposing  and  stimulating  the  stump  of  one 
of  the  cut  posterior  roots.  We  might  suppose  that  the  respiratory 
centre  would  be  similarly  devoid  of  automatism  if  absolutely  free 
from  afferent  stimuli.  It  must  be  mentioned,  however,  that  accord- 
ing to  Sherrington  it  is  possible  to  excite  strychnine  or  asphyxial 
spasms  in  a  dog  or  cat  with  isolated  spinal  cord,  in  which  all  the 
afferent  roots  below  the  transection  have  been  divided  six  or  seven 
hours  previously.  He  therefore  is  of  opinion  that  in  the  mammal 
the  motor  nervous  mechanism  can  be  set  into  activity  apart  from  the 
incidence  of  afferent  impressions.  The  respiratory  centre  tends  to 
respond  to  all  stimuli,  continuous  or  rhythmic,  by  means  of  rhythmic 
discharges,  and  there  can  be  no  doubt  that  if  we  take  the  medulla  in 
connection  with  the  rest  of  the  hind-  and  mid-brain  we  are  justified 
in  regarding  its  activity  as  automatic. 

The  automatic  activity  of  the  heart  is  intimately  dependent  on 
the  sahne  constituents  of  the  blood.  It  may  be  abolished  or  diminished 
by  modifying  these  constituents,  and  can  be  maintained  for  a  consider- 
able length  of  time  by  perfusing  the  heart  with  solutions  containing 
inorganic  salts  in  the  concentration  in  which  they  exist  in  the  blood- 
plasma.  When  we  speak  of  the  automatic  activity  of  the  respiratory 
centre  we  imply  in  the  same  way  that  its  activity  is  dependent  on 
the  normal  composition  of  the  blood  circulating  through  its  vessels. 
In  this  case,  however,  it  is  the  gaseous  contents  of  the  blood 
which  are  of  supreme  importance.  If  the  normal  ventilation  of  the 
lungs  be  prevented,  as  by  hgature  of  the  trachea  or  opening  both 
pleural  cavities,  the  blood  becomes  more  and  more  venous.  As 
this  venous  blood  circulates  through  the  meduUa  the  activity  of  the 
centre  is  continually  increased,  until  finally  the  impulses  discharged 
from  the  centre  may  set  into  activity  practically  every  muscle 
of  the  body,  producing  asphyxial  convulsions.  On  the  other  hand, 
the  activity  of  the  respiratory  centre  can  be  diminished  or  even 
aboUshed  if,  by  an  artificial  ventilation  of  the  alveoli,  we  maintain 
an  over-arteriahsation  of  the  blood,  so  that  the  fluid  passing  to  the 
brain  contains  more  oxygen  and  less  carbon  dioxide  than  is  the  case 
under  normal  circumstances.  What  are  the  factors  involved  in  this 
chemical  regulation  of  respiration  ? 


1204  PHYSIOLOGY 

THE  CHEMICAL  REGULATION  OF  THE  RESPIRATORY 
MOVEMENTS 
If,  the  nervous  centres  being  intact,  the  proper  aeration  of  the 
respiratory  centre  be  interfered  with  in  any  way,  the  respiratory 
movements  increase  in  strength  and  frequency,  and  if  the  disturbing 
factor  be  not  removed  the  animal  dies,  presenting  a  train  of  phenomena 
which  are  classified  together  under  the  term  '  asphyxia.' 

The  phenomena  of  asphyxia  may  be  divided  into  three  stages  : 

(1)  In  the  first  stage,  that  of  hyperfnoea,  the  respiratory  move- 
ments are  increased  in  amphtude  and  in  rhythm.  This  increase 
affects  at  first  both  inspiratory  and  expiratory  muscles.  Gradually 
the  force  of  the  expiratory  movements  becomes  increased  out  of  all 
proportion  to  the  inspiratory,  and  the  first  stage  merges  into  : 

(2)  The  second,  which  consists  of  expiratory  convulsions,  in  which 
almost  every  muscle  of  the  body  may  be  involved.  Just  at  the  end 
of  the  first  stage  consciousness  is  lost,  and  almost  immediately  after 
the  loss  of  consciousness  we  may  observe  a  number  of  phenomena 
extending  to  almost  all  the  functions  of  the  body,  some  of  which  have 
been  already  studied.  Thus  the  vaso-motor  centre  is  excited,  causing 
universal  vascular  constriction.  There  is  often  also  secretion  of 
saUva,  inhibition  or  increase  of  intestinal  movements,  constriction 
of  the  pupil,  and  so  on. 

(3)  At  the  end  of  the  second  minute  after  the  stoppage  of  the 
aeration  of  the  blood,  the  expiratory  convulsions  cease  almost  suddenly, 
and  give  way  to  slow  deep  inspirations.  With  each  inspiratory  spasm 
the  animal  stretches  itself  out  and  opens  its  mouth  widely  as  if  gasping 
for  breath.  The  whole  stage  is  one  of  exhaustion  :  the  pupils  dilate 
widely,  and  all  reflexes  are  aboUshed.  The  pauses  between  the 
inspirations  become  longer  and  longer,  until  at  the  end  of  four  or  five 
minutes  the  animal  takes  its  last  breath. 

If  we  increase  the  activity  of  the  centre,  and  therefore  its  gaseous 
interchanges,  by  warming  the  blood  in  the  carotid  arteries,  there  may 
be  a  considerable  quickening  of  respiration  una«companied  by  any 
deepening,  a  condition  which  is  spoken  of  as  tachypncea.  On  the 
other  hand,  we  may  slow  the  respiratory  movements  by  placing  a 
small  piece  of  ice  on  the  floor  of  the  fourth  ventricle. 

In  the  production  of  the  phenomena  of  asphyxia  two  factors  must 
be  at  work.  In  the  first  place,  there  is  an  accumulation  of  carbon 
dioxide  in  the  blood  batliing  the  centre  or  an  increased  tension  of  this 
gas  in  the  centres  themselves,  either  as  a  result  of  deficient  excretion 
or  increased  production.  On  the  other  hand,  the  centre  is  deprived 
of  oxygen,  either  by  failure  of  renewal  of  the  oxygen  supply,  or  by 
increased  using  up  of  this  gas  in  the  metabolism  of  the  centre.     The 


REGULATION'  OF  RESPIRATORY  MOVEMENTS      1205 

question  arises,  which  of  these  two  changes  is  responsible  for  the 
different  physiological  events  which  characterise  asphyxia  ?  At 
various  times  these  phenomena  have  been  ascribed  either  to  the 
increased  tension  of  carbon  dioxide  or  to  the  diminished  tension  of 
oxygen  in  the  centre.  The  view  that  the  normal  stimulus  to  the 
respiratory  centre  in  asphyxia  was  the  lack  of  sufficient  oxygen  and 
that  the  normal  activity  of  this  centre  was  determined  by  the  tension 
of  oxygen  in  the  blood  circulating^  through  the  brain  was  first  put 
forward  by  Rosenthal.  When  sufficient  oxygen  was  present,  the 
centre,  according  to  this  observer,  would  cease  to  act,  so  that  a  condi- 


FiG.  503.  EfEect  of  COg  on  respiratory  movements  of  rabbit.  (Scott.) 
Upper  line,  tracing  of  diaphragm  slip  (Head's  method).  Lower  tracing, 
carotid  blood  pressure.  During  the  first  period  indicated  on  the  signal  line 
the  animal  breathed  9-6  per  cent.  CO.,  in  air,  and  during  the  second  period 
10  per  cent.  CO.j  with  33  per  cent,  oxygen.  Time  tracing  =  2  sees.  Scale  = 
mm.  Hg.  blood  pressure. 


tion  of  apnaa  would  be  produced.  According  to  Traube,  on  the 
other  hand,  the  special  respiratory  stimulus  was  the  excess  of  carbon 
dioxide  in  the  blood,  and  this  view  was  supported  strongly  by  Miescher. 
The  tendency  of  recent  work,  especially  by  Haldane  and  his  pupils, 
has  been  to  show  that  there  is  an  element  of  truth  in  both  views — 
that  indeed  the  respiratory  centre  can  be  excited  either  by  excess 
of  carbon  dioxide  or  by  lack  of  oxygen,  but  that  its  sensitivity  to 
carbon  dioxide  is  by  far  the  most  important  factor  in  the  determination 
of  the  increased  respiratory  movements  in  asphyxia,  and  is  the  only 
chemical  factor  which  can  be  regarded  as  playing  any  part  in  the 
regulation  of  the  respiratory  movements  under  normal  conditions. 
This  factor  is  well  brought  out  if  we  investigate  the  effect  on  the 
respiratory  movements  of  altering  the  tensions  of  the  two  gases  in  the 
air  breathed.  If  by  this  means  we  succeed  in  altering  the  tension  of 
the  two  gases  in  the  alveolar  air  we  may  assume  that  the  tensions 
of  the  gases  in  the  arterial  blood  leaving  the  lungs  are  altered  in  the 


1206 


PHYSIOLOGY 


same  ratio.  The  results  of  such  experiments  are  very  striking.  Even 
a  slight  increase  in  the  percentage  of  carbon  dioxide  in  the  air  causes 
an  increase  first  in  the  depth  and  later  on  in  the  rhythm  of  respira- 
tion (Fig.  503).  This  is  shown  in  the  following  Table  by  Haldane, 
which  repreg^ents  the  average  depth  and  frequency  of  the  respirations 
when  the  subject  was  breathing  normal  air  and  air  charged  with  vary- 
ing percentages  of  carbon  dioxide.  A  rise  of  carbon  dioxide  in  the 
atmosphere  to  2  per  cent,  increases  the  depth  of  respirations  by  30 
per  cent.,  and  the  total  alveolar  ventilation  by  50  per  cent.  A  rise 
of  carbon  dioxide  to  3  per  cent,  increases  the  total  ventilation  of  the 
alveoli  by  126  per  cent.  An  amount  of  carbon  dioxide  equivalent 
to  6  per  cent,  increases  the  depth  of  each  respiration  by  272  per  cent., 
and  the  total  alveolar  ventilation  by  757  per  cent. 


Percentage  CO. 
in  inspired  air 

Average  depth 
of  respirations 

Average 
frequency  of 
respirations 
per  minute 

Ventilation  of  alveoli 
with  inspired  air 
(normal  =  100) 

COj  percentage 
in  alveolar  air 

0-04 

0-79 
2-02 
.3-07 
5-14 
6-02 

673 

739 

864 
1216 
1771 
2104 

14 

14 
15 
15 
19 

27 

100 

(6-60  litres  per  min.) 

116 

153 

226 
498 

857 

6-6 

5-5 
5-6 
6-5 
6-2 
6-6 

If  we  examine  the  last  column  of  figures  in  this  Table,  representing 
the  percentage  of  CO2  in  the  alveolar  air,  it  will  be  seen  that,  in  spite 
of  the  very  large  variations  in  the  air  breathed,  the  alveolar  content 
in  CO2  remained  practically  constant  until  the  CO2  in  the  atmosphere 
was  increased  to  such  an  extent  that  the  processes  of  compensation 
were  no  longer  efficient.  We  must  conclude  therefore  that  the  respi- 
ratory centre  is  so  arranged  as  to  react  to  the  slightest  increase  of 
CO2  tension  in  the  blood,  any  increase  in  this  gas  giving  at  once  a 
compensatory  increase  in  depth  and  frequency  of  respiration,  so  that 
the  alveolar  CO2  content  may  be  maintained  almost  constant. 

That  it  is  the  tension  of  CO2  in  the  alveolar  air,  and  therefore  in 
the  blood  bathing  the  centres,  and  not  the  percentage  amount  of  this 
gas,  which  is  the  determining  factor  is  shown  by  a  comparison  of  the 
composition  of  the  alveolar  air  under  different  atmospheric  pressures. 
Thus,  when*[the  subject  of  the  experiments,  from  which  the  above 
Table  was  derived,  was  placed  in  an  air-chamber  compressed  to  a 
pressure  of  1261  mm.,  the  mean  percentage  of  CO2  in  the  alveolar  air 

was  342,  corresponding,  however,  to  a  tension  of  342   x 


760 


5-6 


REGULATION  OF  RESPIRATORY  MOVEMENTS      1207 

per  cent,   of  an   atmosphere,   a   fij^re  almost   identical  with  those 

given  in  the  last  colunm  of  the  Table  above.     At  the  top  of  Ben  Nevis, 

where  the  barometric  pressure  was  646  mm.,  the  percentage  of  COj  in 

646 
the  alveolar  air  was  6*6,  correspondmg  to  a  tension  of  6"  6  X  =7-  = 

5"2  per  cent,  of  an  atmosphere,  i.e.  of  760  mm.  Thus  the  pressure  of 
CO2  in  alveolar  air  remains  practically  constant  with  widely  varying 
limits  of  atmospheric  pressure  and  with  very  different  percentages  of 
CO2  in  the  inspired  air,  showing  that  the  reactions  of  the  organism! 


3000        2600 


2200        1800        1400 
air  pressure  mm  Hg 


Fig.  504.  Effects  of  alterations  in  the  barometric  pressure  on  the  alveolar 
COo  tension,  the  alveolar  COo  percentage,  and  in  the  alveolar  0.,  tension. 
Note  that  the  excitant  effects  of  0.  lack  are  not  seen  until  the  pressure 
falls  below  500  mm.  Hg.     (Boycott  and  Haldake.) 


are  directed  so  as  to  maintain,  by  alterations  in  the  respiratory  depth 
and  rhythm,  a  constant  tension  of  this  gas  in  the  alveoli  and  therefore 
in  the  arterial  blood. 

Very  difEerent  are  the  phenomena  observed  on  alteration  of  the 
partial  pressure  of  oxygen  (Fig.  504).  Here,  within  wide  limits,  the 
partial  pressure  of  oxygen  in  the  alveolar  air  is  determined  bv  its  pres- 
sure in  the  inspired  air.  Thus,  if  we  take  the  same  series  of  observations 
with  a  pressure  of  646  mm.,  the  percentage  of  oxygen  in  the  alveolar 

646 
air  was  1319,  corresponding  to  a  tension  of    13"10    x -z-r-   =  10"4 

per  cent.  At  an  atmospheric  pressure  of  755  mm.  the  percentage 
of  oxygen  in  the  alveolar  air  was  13'97,  corresponding  to  a  tension 
of    13'06  per  cent.,  which  we  may  take  as  the  normal  figure  at  the 


1208  PHYSIOLOGY 

sea-level.     In  air  compressed  to  a  pressure  of  1261  mm.  the  percentage 

•         .        ^  1261 

of  oxygen  was  16"79,  correspondmg  to  a  tension  of  16'/ 9    x   7^--  = 

26*8  per  cent,  of  an  atmosphere  of  760  mm. 

Similar  results  are  obtained  by  altering  the  percentage  of  oxygen 
in  the  air  breathed.  The  oxygen  tension  or  percentage  in  the  inspired 
air  can  be  lowered  from  its  normal  of  20*93  to  12  or  13  per  cent,  without 
altering  in  any  way  the  depth  or  rhythm  of  respiration,  and  in  fact 


Fig.  505.     Effects  of  oxygen  lack.     (Scott.) 
Upper  tracing,  diaphragm  slip;    lower  tracing,  carotid   blood  pressure. 
During  time  indicated  by  signal,  5  per  cent,  oxygen  in  nitrogen  was  inhaled. 
c  =  convulsion 

without  any  change  being  noticed  by  the  individual  who  is  the  subject 
of  the  experiment.  A  percentage  of  13  per  cent,  of  oxygen  corresponds 
to  an  alveolar  content  in  oxygen  of  8  per  cent.,  and  with  a  further 
reduction  of  the  oxygen  content  there  is  increased  pulmonary  ventila- 
tion (Fig.  505),  but  the  diminution  in  oxygen  may  be  pushed  to  such  an 
extent  that  the  patient  becomes  blue  from  the  deficient  aeration  of  his 
haemoglobin,  without  any  considerable  distress  being  caused.  In  fact  in 
many  cases  the  subject  of  such  an  experiment  may  lose  consciousness 
suddenly  before  he  has  been  aware  of  any  serious  deficiency  in  his 
aeration. 

The  difference  in  the  sensitiveness  of  the  centre  to  increase  of 
carbon  dioxide  and  lack  of  oxygen  respectively  is  well  shown  by  an 


REGULATION  OF  RESPIRATORY  MOVEMENTS      1209 

experiment  of  Haldane's,  in  which  the  same  person  breathed  in  and 
out  of  a  bag,  in  the  first  place  allowing  the  carbon  dioxide  produced 
in  respiration  to  accumulate,  and  in  the  second  removing  the  carbon 
dioxide  by  means  of  soda  lime,  so  that  the  sole  effect  of  respiration 
was  to  produce  a  continual  diminution  in  the  percentage  of  oxygen. 
In  the  first  case,  when  the  carbon  dioxide  was  allowed  to  accumulate 
it  was  found  that  extreme  and  intolerable  hyperpnoea  was  produced 
when  the  gaseous  content  of  the  bag  consisted  of  5"  6  per  cent,  carbon 
dioxide  with  14'8  per  cent,  oxygen.  When  the  carbon  dioxide  was 
absorbed  it  was  possible  to  breathe  in  and  out  of  the  bag  for  a  much 
longer  period.  No  hyperpnoea  was  produced,  and  the  experiment 
was  stopped  as  soon  as  the  subject  was  becoming  blue  in  the  face 
and  experienced  shght  throbbing  in  the  head.  The  pulse  frequency 
had  gone  up  from  80  to  108.  The  bag  was  found  to  contain  no  carbonic 
acid  and  only  8-7  per  cent,  oxygen.  In  another  similar  experiment 
the  oxygen  had  been  reduced  to  6'7  per  cent,  before  it  was  necessary 
to  stop  the  experiment.  We  must  conclude  that  the  respiratory 
centre  possesses  a  specific  sensibility  for  carbon  dioxide,  which  deter- 
mines the  normal  depth  and  rhythm  of  the  respiratory  movements. 
Although  the  respiratory  centre,  in  common  with  the  rest  of  the  central 
nervous  system,  is  sensitive  to  and  can  be  excited  by  lack  of  oxygen, 
this  quality  is  rarely  brought  into  play.  Under  all  ordinary  circum- 
stances an  increased  need  for  oxygen  is  associated  with  an  increased 
production  of  carbon  dioxide  in  the  oxidative  processes  of  the  body, 
and  the  augmentation  of  respiration,  produced  by  the  excitatory 
effect  of  a  small  excess  of  carbon  dioxide  tension  in  the  blood,  suflBces 
to  provide  fully  for  the  increased  needs  of  the  organism  for  oxygen. 
The  reactions  of  the  organism  have  not  been  evolved  in  order  to  adapt 
it  to  balloon  ascents  or  experiments  in  respiratory  chambers.  As 
an  example  of  a  normal  adaptation  we  may  take  the  changes  in 
respiration  which  occur  in  an  animal  as  the  result  of  muscular  exercise. 
During  their  activity  a  large  amount  of  carbon  dioxide  is  produced 
in  the  muscles.  The  blood  passing  from  the  muscles  to  the  heart 
will  not  be  able  to  get  rid  of  the  excess  of  the  carbon  dioxide  in  passing 
through  the  lungs,  and  will  reach  the  respiratory  centre  more  higlily 
charged  with  this  gas,  the  tension  of  which  will  be  raised.  The 
respiratory  centre  is  thus  stimulated,  and  the  increased  pulmonary 
ventilation  thereby  produced  lowers  the  alveolar  carbon  dioxide 
pressure,  until  a  point  is  reached  at  which  an  equiUbrium  is  main- 
tained between  the  effect  of  the  increased  production  of  carbon  dioxide 
in  raising  the  arterial  carbon  dioxide  tension  and  that  of  the  increased 
respiratory  activity  in  lowering  it.  Under  these  circumstances  it  is 
found  that  the  increased  consumption  of  oxygen  in  the  contracting 
muscles  is  more  than  compensated,  so  that  the  oxygen  tension  in 


1210  PHYSIOLOGY 

the  alveoli  and  in  the  arterial  blood  is  rather  above  than   below 
normal. 

In  certain  experiments  Zuntz  and  Geppert  found  that  during 
muscular  exercise  the  respiratory  movements  were  increased  to  such 
an  extent  as  to  bring  the  tension  of  carbon  dioxide  in  the  arterial 
blood  below  normal.  In  these  experiments  the  muscular  contractions 
were  produced  by  tetanising,  through  the  spinal  cord,  the  lower  limbs 
of  an  animal.  Under  these  circumstances  the  activity  of  the  muscle 
would  be  associated  with  a  diminished  blood-flow,  so  that  the  contrac- 
tions would  be  carried  out  in  the  absence  of  a  sufficient  supply  of 
oxygen.  In  the  absence  of  sufficient  oxygen  muscular  contractions 
result  in  the  production,  not  of  carbon  dioxide,  but  of  lactic  acid,  and 
it  is  highly  probable  that  in  the  experiments  in  question  there  was 
a  discharge  of  acid  substances  into  the  blood,  diminishing  the  alka- 
linity of  this  fluid  and  therefore  lowering  its  carrying  power  for  carbon 
dioxide.  As  a  matter  of  fact,  one  can  produce  dyspnoea  by  diminish- 
ing the  alkalinity  of  the  blood  by  the  injection  of  acids,  and  attacks 
of  dyspnoea  are  observed  in  the  later  stages  of  diabetes,  when  the 
alkalinity  of  the  blood  is  decreased  in  consequence  of  the  production 
of  such  bodies  as  oxybutyric  acid.  This  dyspnoea  has  been  ascribed 
to  the  fact  that  a  diminished  carrying  power  of  the  blood  for  carbon 
dioxide  will  raise  the  tension  of  this  gas  in  the  tissues  where  it  is 
formed,  so  that  a  diminished  alkalinity  of  the  blood  may  cause  a 
higher  tension  of  carbon  dioxide  around  the  respiratory  centre.  It 
has  been  shown  by  Kyff el  that  even  a  short  period  of  sufficiently  violent 
muscular  exercise,  i.e.  one  giving  rise  to  dyspnoea,  causes  a  subsequent 
increase  of  lactic  acid  in  the  urine,  and  that  the  blood  itself  at  the 
close  of  the  period  of  exercise  contains  a  demonstrable  amount  of 
this  acid.  Thus  in  one  case  the  urine,  passed  thirty  minutes  after 
running  one-third  of  a  mile  in  two  minutes,  contained  454  mg. 
lactic  acid  as  against  a  normal  excretion  of  between  3  and  4  mg. 
of  lactic  acid  per  hour.  In  another  experiment  blood  was  obtained 
from  the  fore-arm  before  exercise,  immediately  after  exercise,  and 
three-quarters  of  an  hour  later.  The  exercise,  which  consisted  of 
running  rapidly,  lasted  two  minutes  forty-five  seconds.  The  following 
Table  represents  the  results  obtained  : 

Lactic  acid 
per  100  CO. 

Blood  before  starting 12-5  mg. 

Blood  immediately  after  stopping     .  .         .     70-8     ,, 

Blood  45  minutes  later    .....     15-9     ,, 

The  production  of  lactic  acid  during  muscular  exercise  may  thus 
be  regarded  as  a  second  line  of  defence  for  the  organism,  tending  to 
maintain  the  increased  ventilation  of  the  lungs  even  when  the  supply 


REGULATION  OF  RESPIRATORY  MOVEMENTS      1211 

of  oxygen  is  insufficient  to  oxidise  completely  the  materials  consumed 
in  the  production  of  the  muscular  energy.  This  acid  mechanism  is, 
however,  only  employed  when  the  supply  of  oxygen  lags  behind  the 
respiratory  needs  of  the  body  (cp.  Fig.  506).  Ordinary  exercise,  even 
when  considerable,  e.g.  a  twenty-four  hours'  track  walking  race,  does 
not  cause,  as  RyfEel  has  shown,  any  appreciable  increase  in  the  elimina- 
tion of  lactic  acid  by  the  urine.  Under  normal  circumstances  the  depth 
and  rhythm  of  respiration  depend  on  the  carbon  dioxide  pressure  in 
the  respiratory  centre,  a  rise  of  02  per  cent,  of  an  atmosphere  in  the 
tension  of  this  gas  in  the  alveoli  being  sufficient  to  double  the  amount 
of  alveolar  ventilation  during  rest. 

The  first  phase  in  the  phenomena  of  asphyxia  is  thus  conditioned 


-/^C'                u. 

^^''      ^^""^ 

Ji^A    ^^ 

r-rr    y 

rrry 

-,W'   J 

tlLJ^ 

tut 

-^M-t 

tt^L 

I'l  / 

^'iv 

''^aZ^ 

^-'3 

'    -^2'^'^ 

^^" 

Fig.  506.  Dis.sociation  curve  of  oxj'haemoglobm  in  defibrinated  cat's  blood. 
1,  cat  I,  after  partial  occlusion  of  trachea  and  fifteen  minutes  breathing  of 
gas  of  increasing  poverty  in  oxygen  ;  4.  cat  II,  at  beginning  of  experiment ; 
3.  cat  II,  after  fifteen  minutes  gas  respiration ;  2,  after  twenty-one  minutes 
ditto. 

simply  by  the  changes  in  the  carbon  dioxide  tension.  A  little  later 
the  gradual  exhaustion  of  oxygen  in  the  blood  roimd  the  centre  begins 
to  make  itself  felt.  The  respiratory  centre  shares  with  the  rest  of 
the  central  nervous  system  a  sensitiveness  to  the  absence  of  oxygen, 
deprivation  of  oxygen  having  first  an  excitatory  and  later  a  paraMic 
effect.  In  asphyxia  the  first  centres  to  feel  this  effect  are  those  of 
the  cortex,  and  during  the  first  stage  there  is  mental  excitation  ter- 
minating rapidly  in  abohtion  of  consciousness.  During  the  second 
stage  there  is  a  discharge  of  energy,  which  spreads  throughout  the 
whole  nervous  system,  beginning  in  tlie  bulbar  centres  and  causing 
a  great  rise  of  blood  pressure  with  slowing  of  the  heart,  and  extending 
thence  to  all  the  spinal  centres  with  the  production  of  muscular 
spasms.      At  this  stage  too  there  is  a  discharge  of  impulses  giving 


1212  PHYSIOLOGY 

contraction  of  the  pupil,  and  a  discharge  along  the  whole  sympathetic 
system,  producing  the  various  phenomena  of  vaso-constriction, 
erection  of  hairs,  sweating,  salivation,  which  are  generally  brought 
about  by  stimulation  of  different  parts  of  this  system.  The  phenomena 
of  the  third  stage  are  due  to  exhaustion  of  the  nerve-centres,  accom- 
panied or  preceded  by  exhaustion  and  dilatation  of  the  heart,  the 
circulation  failing  before  the  excitation  of  the  lower  centres  has 
entirely  come  to  an  end.  In  this  third  stage  it  is  impossible  by  the 
strongest  stimuli  to  evoke  any  reflex. 

Considerable  discussion  has  taken  place  as  to  the  exact  nature  of  the  stimu- 
lation brought  about  by  want  of  oxygen.  The  blood  of  animals  which  have  been 
killed  by  asphyxia  is  known  to  contain  reducing  substances,  so  that  oxygen 
added  to  it  disappears  and  cannot  be  recovered  in  a  vacuum.  Pfliiger  therefore 
suggested  that  it  was  these  reducing  substances  themselves  which  were  effective 
exciting  agents.  It  was  shown  many  years  ago  by  Hoppe-Seyler  and  his  pupils 
that  in  conditions  of  chronic  oxygen  starvation  there  was  an  excessive  production 
of  lactic  acid  in  the  body,  and  we  have  seen  that  the  same  is  true  for  the  isolated 
muscle  and  that  to  these  substances  has  been  ascribed  (Zuntz  and  Geppert)  the 
excitation  of  the  respiratory  centre  which  occiu's  in  violent  muscular  exercise. 
Haldane  has  suggested  that  in  the  hyperpnoea  and  convulsions  which  occur  as 
the  result  of  breathing  mixtures  with  very  low  percentages  of  oxygen  the  effective 
stimulus  is  also  lactic  acid.  Experiments  were  carried  out  by  Ryffel  on  individuals 
who  had  been  subjected  in  a  respiratory  chamber  to  very  low  oxygen  tensions, 
sufficient  to  cause  cyanosis,  so  that  their  oxygen  alveolar  tension  was  only  about 
6  per  cent.  After  an  experiment,  lasting  four  hours,  there  was  a  definite  increase 
of  lactic  acid  in  the  blood  of  the  fore-arm  (up  to  23-6  mg.  lactic  acid  per  100  c.c). 
After  one  lasting  only  fifteen  minutes,  in  which  the  oxygen  shortage  became  very 
marked,  no  increase  could  be  detected.  When  we  expose  an  animal  such  as  a 
rabbit  to  low  percentages  of  oxygen,  the  hyperpncea  so  produced  disappears 
almost  immediately  when  a  larger  percentage  of  oxygen  is  supplied  to  the  animal, 
whereas  that  produced  by  carbon  dioxide  excess  dies  away  slowly  on  exposiire  to 
normal  conditions.  It  would  seem  that  when  the  exposure  to  low  oxygen  tensions 
is  of  short  duration  no  lactic  acid  is  produced  in  the  blood.  If  therefore 
we  ascribe  the  hyperpnoea  to  the  production  of  lactic  acid  we  must  locate  the 
production  of  this  acid  in  the  respiratory  centre  itself.  Tlaere  are  no  inherent 
improbabilities  in  such  an  assumption,  but  it  is  difficult  at  present  to  see  how  it 
can  be  put  to  the  test  of  experiment. 

In  dealing  with  the  question  of  the  blood  alkalinity  we  defined  neutrality 

as  a  condition  in  which  there  was  equivalent  concentration  of  H  and  OH  ions. 

In  the  blood  the  H  ion  concentration  is  about  0-3  x  10  ~  'N.     The  alkalinity 

concentration  OH  ions 

IS  expressed  bv — :r—-. .     The  acids  and  bases  of  the  blood-serum 

'    concentration  H  ions 

and  of  the  tissue-fluids   generally  are  in  such  proportions  as  to  maintain   the 

approximate  neutrality  of  these  fluids  even  after  considerable  additions  of  acid 

or  alkali.     Thus  hydrochloric  acid  may  be  added  to  the  extent  of  -025  N,  or  NaOH 

to  the  extent  of  -005  N,  without  causing  any  marked  alteration  in  the  reaction  of 

the  blood.     Although,  however,  the  change  produced  by  the  addition  of  acids  or 

alkalies  is  so  minute,  it  is  appreciable  by  electrical  methods,  and  it  may  still  more 

readily  be  appreciated  by  and  act  as  a  stimulus  for  the  cells  of  the  body  themselves. 

Thus  we  have  not  yet  succeeded  in   determining  electrically   the   change  in 

hydrogen  ion  concentration  caused   by   the  change  from  arterial   to   venous 


REGULATION  OF  RESPIRATORY  MOVEMENTS      1213 

blood.  If,  however,  blood-serum  bo  saturated  \vith  carbon  dioxide  at  a  full 
atmosphere,  the  concentration  of  the  hydrogen  ions  rises  to  l-4xlO~"N, 
while  after  removing  the  greater  part  of  the  carbon  dioxide  from  the  same 
senim  by  the  passage  of  a  stream  of  air,  the  concentration  of  the  hydrogen 
ions  sinks  to  -008  x  10~'N.  As  the  respiratory  centre  responds  to  such 
minute  changes  of  concentration  as  would  be  expressed  by  a  difference  of 
0-2  per  cent,  of  an  atmosphere  in  the  carbon  dioxide  tension  of  the  circulating 
blood,  it  must  possess  a  sensitivity  greater  than  any  of  our  physical  means 
for  measuring  the  concentration  of  hydi'ogen  ions  in  a  fluid.  We  may 
approach  this  delicacy  of  reaction  by  using  a  large  molecule  as  our  indi- 
cator. Thus,  as  we  have  seen,  the  dissociation  curve  of  haemoglobin  is  sensi- 
tive to  the  change  in  reaction  caused  by  raising  the  tension  of  carbon  dioxide 
in  the  hienioglobin  solution  by  10  mm.  Hg.  (cp.  Eig.  495). 

The  regulating  factor  in  the  blood  is  probably  not  carbon  dioxide  nor  any 
special  acid,  but  the  concentration  of  hydrogen  ions  in  this  fluid  or  in  the  cells 
of.  the  centre  itself.  Such  a  conclusion  brings  under  one  head  all  the  several 
factors  which  we  know  to  act  upon  the  respiratory  centre,  namely,  tension  of 
carbon  dioxide,  presence  of  acids  in  the  blood — especially  lactic — and  considerable 
diminution'  of  oxygen  supply  to  the  cells.  The  respiratory  centre  Avould  then 
not  differ  qualitatively  from  any  other  part  of  the  central  nervous  sj^stem.  Its 
special  function  would  be  determmed  simply  by  the  evolution  to  a  marked  degree 
of  a  sensibility  to  hydrogen  ions  which  is  already  possessed  by  the  whole  of  the 
central  nervous  system  and  indeed  by  practically  every  tissue  of  the  body. 

We  may  conclude  that  mere  lack  of  oxygen  is  not  to  be  regarded 
in  itself  as  an  excitatory  agent.  Its  influence  will  be  rather  to  paralyse 
all  activity.  On  the  other  hand,  excitation  is  caused  by  the  products 
of  metabolism,  which  vary  according  as  the  oxygen  supply  is  ample 
or  insufficient  for  the  needs  of  the  cells.  In  the  former  case  activity 
results  in  the  production  of  carbon  dioxide,  in  the  latter  of  lactic 
acid,  and  perhaps  other  substances.  Both  these  are  acid  substances 
and  their  production  will  therefore  raise  the  concentration  of  the 
hydrogen  ions  in  the  cells  where  they  are  produced  as  well  as  in  the 
blood.  The  nerve-centres  are  extremely  sensitive  to  minute  changes 
in  the  hydrion  concentration  either  in  themselves  or  in  the  fluids 
surrounding  them,  and  are  thrown  into  activity  by  excess  of  these 
ions  and  inhibited,  or  put  to  rest,  by  relative  deficiency  of  the  ions. 
In  their  relation  to  H  and  OH  ions  respectively  the  medullary  centres 
have  a  sensibiUty  five  times  as  great  as  the  spinal  centres.  The 
condition  of  apnoea,  which  is  associated  not  only  with  cessation  of 
respiratory  movements  but  also  with  fall  of  blood  pressure,  may  be 
ascribed  to  relative  increase  in  the  OH  ions  or  diminution  in  the 
H  ions. 

Since  tlic  auiiual  has  developed  a  mechanism  by  means  of  which 
changes  in  the  reaction  of  the  blood  can  be  rapidly  adjusted  by  varying 
the  excretion  of  carbon  dioxide,  whilst  the  excretion  of  other  acids 
is  relatively  slow,  carbon  dioxide  may  be  regarded  as  the  normal 
respiratory  hormone,  and  so  far  we  may  agree  with  Henderson  in 


1214  PHYSIOLOGY 

regarding  carbon  dioxide  as  maintaining  the  activities  of  the  various 
nerve-centres  at  their  nornnl  level.  But  it  is  the  hydrion  concentra- 
tion which  appears  to  be  the  essential  factor,  and  the  acid  substances 
produced  during  oxygen  lack  are  equally  efficacious,  but  not  so  con- 
venient. Thus  their  production  is  not  a  steady  process  like  that  of 
carbon  dioxide,  but,  as  Mathison  points  out,  commences  suddenly  at 
a  time  when  the  executive  side  of  the  nerve -cell  is  feeling  the  effect 
of  oxygen  starvation,  so  that  the  cell  may  be  too  much  disorganised 
to  respond  to  stimulation.  "  The  broad  margin  of  safety  protecting 
the  organism  against  paralysis  of  its  cells  by  oxygen  starvation  is 
assured  by  the  sensitiveness  of  the  medullary  centres  to  hydrogen 
ion  concentration  and  therefore  to  carbon  dioxide  in  common  with 
other  acids." 

On  the  other  hand,  it  must  be  remembered  that  excessive  produc- 
tion of  hydrogen  ions  may  finally  result  in  a  condition  of  paralysis, 
which  in  the  nervous  centres  is  expressed  by  narcosis.  These  effects 
can  only  be  removed  by  a  free  supply  of  oxygen.  The  concentration 
at  which  these  results  occur  varies,  as  we  have  seen,  in  different  parts 
of  the  nervous  system  and  also  in  different  tissues.  Thus  on  the 
heart  a  shght  increase  in  H  ion  concentration  causes  diminished  tone, 
which  may  at  first  have  a  salutary  effect  on  the  total  work  of  the 
heart,  but  later  leads  to  dilatation  and  failure  of  this  organ.  The 
same  effect  is  produced  on  the  unstriated  muscle  fibre  of  the  blood- 
vessels. Since  in  the  heart  and  blood-vessels  the  reverse  effect  is 
produced  by  increasing  the  OH  ion  concentration,  it  is  evident  that 
the  line  of  '  physiological '  neutrality  at  which  neither  stimulation  nor 
paralysis  is  produced  must  vary  in  different  tissues. 

It  is  an  interesting  question  whether  the  electrical  excitation  of 
nerves  may  not  be  due  to  a  similar  alteration  in  the  hydrion  concentra- 
tion at  the  cathode  which  is  the  seat  of  stimulation.  If  this  were  so, 
all  the  activities  of  protoplasm  might  be  regarded  as  determined  by 
the  relative  concentration  of  the  H  and  OH  ions  within  the  cells  or 
in  the  medium  surroimdiug  the  cells. 

THE  REFLEX  NERVOUS  REGULATION  OF  RESPIRATION 

Although  the  specific  sensibility  of  the  respiratory  centre  to  CO2 
is  the  most  important  factor  in  determining  the  depth  and  rhythm 
of  the  respiratory  movements,  these  movements  and  the  condition 
of  the  respiratory  centre  itself  are  modified  in  a  large  degree  by  impulses 
arriving  at  the  centre  along  both  vagi.  Through  other  sensory 
nerves  of  the  body  the  respiratory  movements  can  be  altered  reflexly, 
but  it  is  onl^  through  the  vagi  that  a  continuous  stream  of  impulses 
passes  to  the  centre  under  normal  circumstances,  so  that  every  respira- 
tory movement  is  modified  by  these  impulses. 


REGULATION  OF  RESPIRATORY  MOVEMENTS      1215 

In  studying  the  nervous  mechanism  of  respiration,  it  is  necessary  to  have 
some  accurate  method  of  recording  the  respiratory  movements.  They  may  be 
registered  by  means  of  a  tambour  applied  to  the  chest,  commimicating  with 
another  tamboiu:  provided  Avith  a  lever,  which  is  arranged  to  write  on  a  blackened 
surface  ;  or  a  side  tube  to  a  camiula  in  the  trachea  may  be  connected  with 
the  registering  tambour.  In  the  first  case  movements  of  the  thorax  are  registered ; 
in  the  second  changes  of  intra-pulmonary  pressure.  These  methods  are  obviously 
useless  when  it  is  wished  to  study  the  effects  of  artificial  distension  or  collapse 
of  the  lungs.  In  this  instance  we  may  use  the  ingenious  method  described  by 
Head.  In  the  rabbit  a  slip  of  the  diaphragm  on  either  side  of  the  ensiform 
cartilage  is  so  disposed  that  the  end  of  it  may  be  freed  and  attached  by  a  thread 
to  a  lever  without  injury  to  its  blood-  or  nerve-supply.     It  is  found  that  this 


Fig.  507.     Normal  tracing  of  diaphragm  sUp  (Head's  method). 

slip  contracts  synchronously  with  the  rest  of  the  diaphragm,  so  that  it  serves  as 
a  sample  of  the  diaphragm,  the  contractions  of  which  may  be  recorded  uninfluenced 
by  passive  movements  of  the  chest  wall  or  artificial  increase  of  intra-pulmonary 
pressure. 

If,  while  the  respiratory  movements  are  being  recorded  in  one  of 
the  afore-mentioned  ways,  both  vagi  be  divided,*  a  marked  change 
in  the  respiratory  rhythm  is  at  once  seen.  The  first  effect  is  an  increased 
inspiratory  tonus,  but  this  rapidly  disappears,  arid 'the  respiratory 
movements  become  less  frequent  and  are  increased  in  amplitude.  If 
now  the  central  end  of  one  of  the  vagi  be  stimulated  with  an  interrupted 
current,  the  respiration  may  be  quickened,  or,  as  is  more  coramonly  the 
case,  the  inspiratory  movements  may  be  increased  at  the  expense 
of  the  expiratory,  so  that  finally  a  condition  of  inspiratory  standstill 
is  produced,  and  the  slip  of  the  diaphragm  enters  into  prolonged 
contraction. 

With  a  very  weak  stimulus  it  is  sometimes  possible  to  produce 
augmentation  of  the  expiratory  movements  or  rather  inhibition  of  the 
inspiratory,  and  this  is  the  invariable  result  of  passage  of  a  constant 
current  through  the  vagus  in  an  ascending  direction.   This  effect  may 

*  The  division  of  the  vagi  is  best  effected  by  putting  them  on  a  hooked 
copper  wire,  of  which  the  upper  end  is  inserted  in  a  freezuig-mixture.  Li  this  way 
complete  functional  division  of  the  nerves  is  obtained  without  any  excitation. 
If  the  nerves  be  cut,  a  eertam  amount  of  stimulation  takes  place  in  constjquence 
of  the  closure  of  the  demarcation  exurent  produced  by  the  cross-section. 


1216 


PHYSIOLOGY 


be  more  strikingly  brought  about  by  stimulation  of  the  central  end 
of  the  superior  laryngeal  nerve,  which  produces  first  an  inhibition  of 
inspiration,  so  that  the  respiratory  muscles  come  to  a  standstill  in  the 
position  of  expiration,  and  then  a  forcible  contraction  of  the  expiratory 
muscles.  This  illustration  of  the  presence  of  expiratory  fibres  in  the 
superior  laryngeal  nerve  is  not  confined  to  laboratory  experience,  but 
is  constantly  occurring  in  everyday  life.    The  superior  laryngeal  nerve 

supplies  sensory  fibres  to  the  mucous 
membrane  of  the  glottis,  and  we  know 
that  the  slightest  irritation  of  these 
fibres — the  presence  of  a  crumb  or  a 
particle  of  mucus — causes  forcible 
expiratory  spasms,  with  spasmodic 
closure  of  the  glottis,  which  we  term 
a  cough.* 

So  we  see  that  the  vagus  nerve 
contains  two  kinds  of  afferent  fibres,  or 
at  any  rate  afferent  fibres  with  two 
distinct  functions.  Stimulation  of  the 
one  kind  stops  inspiration  and  produces 
expiration ;  stimulation  of  the  other 
stops  expiration  and  produces  inspira- 
tion. Since  section  of  both  vagi  causes 
slowing  of  respiration,  impulses  which 
exert  some  influence  on  the  respiratory 
centre  and  quicken  respiration  must 
travel  up  the  vagi  from  the  lungs.  The 
respiratory  movements  cause  an  alter- 
nate distension  and  contraction  of  the 
lungs,  and  it  has  long  been  thought 
that  it  is  these  changes  in  the  volume 
of  the  lungs  which  start  the  accelera- 
ting impulses  that  travel  up  the 
vagus  nerves.  To  test  the  truth  of  this  hypothesis  it  is  necessary  to 
study  the  two  phases  of  respiration  separately ;  that  is,  to  see  first 
the  result  on  the  respiratory  impulses  of  distension  of  the  lungs,  and, 
secondly,  the  result  of  a  sudden  collapse  or  a  contraction  caused  by 
sucking  air  out  of  the  lungs.  The  effects  of  distension  or  collapse 
of  the  lung  may  be  shown  by  simply  closing  the  trachea  at  the  end 

*  It  must  not  be  imagined  that  the  fibres  of  the  superior  larjTigeal  nerves 
are  concerned  in  the  reflex  maintenance  of  the  normal  respiratory  rhythm. 
They  are  cited  here  merely  because  the  result  of  their  stimulation  resembles 
that  which  would  be  caused  by  stimulation  of  the  analogous  expiratory  fibres 
which  run  in  the  trunk  of  the  vagus  from  the  lungs  to  the  respiratory  centre. 


Fig.  508.  Effects  of  distension — 
collapse  of  lung.  Both  curves  are 
described  by  a  lever  attached  to  a 
slip  of  the  diaphragm  of  a  rabbit. 
A  contraction  of  the  diaphragm 
(inspiration)  raises  the  lever;  dur- 
ing relaxation  of  the  diaphragm 
the  lever  falls. 

In  A,  the  trachea  is  closed  at  x, 
the  height  of  inspiration  ;  a  pause 
follows,  during  which  the  lever 
gradually  sinks  until  an  inspiration 
(a  very  powerful  one)  sets  in. 

In  B,  the  trachea  is  closed  at  the 
end  of  expiration,  x  ;  there  follow 
powerful  inspirations.   (Foster.) 


REGULATION"  OF  RESPIRATORY  MOVEMENTS       1217 

of  inspiration  or  of  expiration.     The  results  of  such  an   experiment 
are  shown  in  Fig.  508. 

A  still  more  marked  effect  is  produced  if  the  lungs,  by  means 
of  a  tube  in  the  trachea,  be  artificially  inflated  or  if  air  be  sucked 
out  of  them.  The  inflation  produces  an  instantaneous  and  com- 
plete relaxation  of  the  diaphragm  (Fig.  509)  which  by  clamping 
the  tracheal  tube  may  be  prolonged  for  several  seconds,  while 
sucking  air  out  of  the  lungs  causes  a  tonic  contraction  of  the 
diaphragm  (Fig.  510).    Somewhat  similar  results  may  be  obtained 


Pos.  vcntilatiou 


Fig.  509.     Positive  ventilation.     (Head.) 
Under  the  influence  of  positive  ventilation,  the  inspiratory  contractions 
of  the  diaphragm  become  less  and  less  till  they  disappear  completsly. 


Fig.    510.     Negative  ventilation.     (He.\d.) 
At  «  negative  ventilation  was  commenced.     The  expiratory  rehixation  of 
the  diaphragm  is  seen  to  become  more  and  more  incomplete,  until  it  tinally 
enters  into  continued  contraction. 

by  repeatedly  inflating  or  deflating  the  lungs  (positive  and  nega- 
tive ventilation).  The  effects  here  are  complicated  by  the  fact  that 
one  is  dealing  in  both  cases  with  alternating  movenients  of  the 
lungs,  of  expansion  and  contraction,  both  of  which  will  have  an  influence 
on  the  respiratory  centre.  Moreover  repeated  forcible  inflation  of 
the  lungs  increases  the  ventilation  of  the  pulmonary  alveoli,  thus 
lowering  the  normal  carbon  dioxide  tension  of  tlie  lungs.  As  a  result 
of  repeated  ventilation  we  may  obtain  a  condition  of  respiratory 
standstill.  In  this  condition,  however,  as  we  shall  see  later,  the 
determining  factor  is  rather  chemical  than  mechanical. 

■These    inhibitory    and    augmentor    effects    of    changes    in    the 
^olunjie  of  the  lung  must  also  result  from  the  normal  movements  of 

77 


1218  PHYSIOLOGY 

these  organs  in  respiration.  Let  us  consider,  for  instance,  what  will 
happen  if  the  influence  of  the  two  vagi  could  be  suddenly  throw^n  in 
after  these  nerves  have  been  divided.  (This  experiment  can,  in  fact, 
be  realised  more  or  less  completely  if  the  functional  division  of  the  vagi 
be  effected  by  cooling  or  by  ether  narcosis.)  The  animal  would  be 
breathing  slowly  and  deeply.  If  at  the  beginning  of  an  inspiration 
the  vagi  become  functional  the  expansion  of  the  lungs  caused  by  the 
inspiratory  movement  would  send  inhibitory  impulses  up  to  the  vagus 
centre,  which  would  stop  the  movement  of  inspiration.  The  movement 
of  expiration  would  then  begin,  and  the  collapse  of  the  lungs  thereby 
produced  w^ould  itself  send  impulses  up  the  vagi  which  would  tend 
to  excite  an  inspiratory  movement.  Both  inspiration  and  expiration 
would  therefore  be  shortened,  and  the  successive  movements  would 
follow  one  another  at  a  shorter  interval  than  if  the  vagi  were  not 
functional.  In  this  way,  under  normal  circumstances,  the  rhythm 
of  the  respiratory  centre  must  be  determined  reflexly  through  the  agency 
of  the  vagi,  while  the  chief  factor  in  determining  the  total  pulmonary 
ventilation  is,  as  Ave  have  seen,  the  carbon  dioxide  tension  of  the 
blood. 

In  the  foregoing  account  we  have  spoken  of  the  expiratory  and  inspiratory 
effects  of  the  vagus  as  if  they  were  of  equal  importance.  It  seems  probable, 
however,  that  the  inhibitory  or  expiratory  impulses  started  by  the  inspiratory 
movement,  the  only  or  the  more  active  part  of  normal  respiration,  plaj^  a  more 
prominent  part  in  the  regulation  of  respiration  than  do  the  inspiratory  impulses  ; 
and  one  observer  (Gad)  goes  so  far  as  to  deny  altogether  the  existence  of  two  kinds 
of  respiratory  fibres  in  the  vagus.  According  to  Gad,  the  vagus,  as  regards  the 
respiratory  centre,  is  a  purely  inhibitory  nerve.  Hence  the  primary  effect  of 
dividing  both  vagi  is  an  increased  inspiratory  tone.  This  view  at  first  seems 
paradoxical,  in  that  it  explains  the  final  slowing  of  respiration  after  section  of 
the  vagi  as  due  to  the  cutting  off  of  previous  inhibitory  impulses.  But  inhibition 
in  all  tissues  has  a  twofold  effect.  Although  the  immediate  effect  is  diminution  of 
activity,  yet  the  diminished  disintegration  necessarily  associated  with  diminished 
activity  means  an  increase  of  the  anabolic  at  the  expense  of  the  catabolic  processes 
of  the  tissues.  In  this  way  we  explained  the  diminished  excitability  occurring 
in  a  nerve  at  the  anode  of  a  constant  current,  and  it  will  be  remembered  that 
the  secondary  result  of  anelectrotonus  was  increased  irritability  and  con- 
sequent excitation  at  break  of  the  constant  current.  The  same  sort  of  process 
must  occur  in  the  respiratory  centre.  A  continued  restraint  of  its  rhythmic 
activity  must  lead  to  a  heaping  up  of  its  irritable  material,  so  that  the  final 
result  is  a  state  of  hyperexcitability  in  which  the  centre,  so  to  speak,  boils  over 
on  the  slightest  provocation. 

In  this  condition  a  cutting  off  of  the  inhibitory  impulses  must  at  first  increase 
the  activity  of  the  centre,  leading  to  the  increased  inspiratory  tonus  already 
described.  But,  unchecked  by  anj'  reining  impulses,  the  centre  enters  upon  a 
career  of  spendthrift  activity.  Each  inspiratory  contraction  is  maximal,  but  the 
centre,  exhausted  by  the  effort,  has  to  wait  a  considerable  time  before  it  can 
accumulate  sufficient  energy  for  the  next  ;  hence  the  final  result  of  section  of 
both  vagi  is  deepening  and  slowing  of  respiration. 

Although  Gad  has  rendered  great  service  in  emphasising  the  importance  of 


REGULATION  OF  RESPIRATORY  MOVEMENTS       1219 

the  inhibitory  or  expiratory  impulses  which  ascend  the  vagi,  there  is  no  doubt 
that  he  went  too  far  in  denying  the  existence  of  inspiratory  fibres  in  the  vagus. 
This  is  shown  by  the  following  experiment  of  Head.  According  to  Gad's  view, 
collapse  of  both  lungs  implies  simply  a  removal  of  the  normal  inhibitory  impulses 
ascending  the  vagi,  and  is  therefore  equivalent  to  division  of  these  two  nerves. 
]f  in  the  rabbit  the  left  vagus  be  divided,  a  tube  can  be  introduced  into  the 
left  bronchus,  and  artificial  respiration  can  be  ijerfornied  by  alternate  inflation 
and  collapse  of  the  left  lung,  without  in  any  way  affecting  the  respiratory  centre, 
all  connections  with  the  latter  being  destroyed  (v.  Fig.  511).  Meanwhile  the 
animal  carries  out  normal  respiratory  movements,  which  can  be  recorded  by 
the  diaphragm  slip  method.  While  the  slip  is  contracting  regularly,  the 
right  pleiu-a  is  opened  and  the  right  lung  allowed  to  collapse.  The  effect  of  this 
collapse  carried  up  by  the  right  vagus  to  the  centre  is  an  extreme  contraction 


RT  Lung, 


artif  resp  app. 


L^  Lun 


Fig.  oil.    Diagram  to  illustrate  Head's  experiment  on  the  eliect  of  collapse  of  the 
lung.     E.c,  respiratory  centre  ;   R.v,  L.v,  right  and  left  vagi. 

of  the  diaphragm,  and  since  the  onset  of  asphyxia  is  prevented  by  the  arti- 
ficial respiration  carried  out  on  the  left  lung,  the  tonic  standstill  of  the  dia- 
phragm may  last  over  a  minute.  In  tliis  case  therefore  the  effect  of  collapse 
of  one  lung  is  enormously  greater  than  that  produced  by  section  of  both  vagi, 
showing  that  the  effect  is  due,  not  to  abolition  of  the  ordinary  tonic  inhibitory 
st  imuli.  but  to  excitation  of  special  inspiratory  fibres  in  the  vagus  by  the  collapse 
of  the  lung. 

By  means  of  the  string  galvanometer  it  is  possible  to  show  definitely  that  a 
collapse  of  the  lungs  does  set  up  a  nervous  impulse  travelling  up  the  vagus 
nerves.  This  impulse  must  be  inspiratory  in  character,  so  that  there  is  no  reason 
to  deny  the  existence  of  both  kinds  of  fibres  in  these  nerves.  The  effects  of 
electrical  stinudation,  especially  with  an  ascending  constant  current,  is  also 
strong  evidence  in  the  same  direction. 

After  division  of  botli  vagi  the  total  ]niliii(>n;irv  ventilation  does 
not  as  a  rule  nnderuo  any  marked  cluinues.  and  in  the  absence  of 
anaesthesia  the  aeration  of  the  blood   mav  be  carried   out  almost, 


1220  PHYSIOLOGY 

if  not  quite,  as  well  as  in  the  intact  animal.  The  importance  of 
the  vagus  action  for  the  organism  is  shown,  however,  if  we  put 
an  increased  strain  on  the  respiratory  mechanism,  as,  for  instance, 
by  increasing  the  percentage  of  carbon  dioxide  in  the  air  breathed. 
In  the  intact  animal  this  procedure  leads  first  to  increased  depth  and 
later  to  increased  frequency  of  respiration,  the  total  ventilation 
being  thereby  augmented  to  such  an  extent  as  to  keep  the  alveolar 
tension  of  carbon  dioxide  almost  constant.  If  the  same  percentage  of 
carbon  dioxide  be  administered  to  an  animal  after  section  of  both  vagi 
the  effect  is  deepening  of  respiration,  but  not  quickening  (Fig.  512). 
Each  inspiratory  movement,  however,  is  already  considerable  so 
that  the  margin  by  which  increase  of  pulmonary  ventilation  is  possible. 


?*^iiHiiiiii 


•mmHmmm' 


^Yvvv^wfV\Yv^'V^f^wv\'VV^^M'^Aw^^^/^^ 


A,AWVvv«r 


Fig.  512.  Effect  of  10'6  per  cent.  CO.,  in  a  mixture  containing  23-3Jper  cent.  O., 
on  a  rabbit  vnth  both  vagi  divided.  The  gas  was  administered  between  the 
arrows.  Zero  line  of  blood  pressure  is  32  mm.  below  bottom  of  tracing. 
Compare  this  figure  with  Fig.  503,  p.  1205.     (F.  H.  Scott.) 

by  increase  of  depth  of  respiration  alone,  is  not  so  great  as  in  a  normal 
animal.  Moreover,  since  no  quickening  of  respiration  takes  place, 
the  increased  ventilation  rapidly  becomes  inadequate  for  the  main- 
tenance of  the  normal  alveolar  carbon  dioxide  tension.  In  the  Table 
on  p.  1221  the  total  amounts  of  pulmonary  ventilation  obtained  on 
administration  of  mixtures  containing  carbon  dioxide  to  a  rabbit 
before  and  after  section  of  the  vagi  are  compared. 

Whether  we  assume  that  the  prevailing  impulses  travelling  up  the 
vagi  are  purely  inhibitory  or  are  both  inhibitory  and  augmentor, 
the  resultant  effect,  by  reining  in  the  activity  of  the  centre,  is  to  econo- 
mise its  energy  and  the  energy  of  the  respiratory  muscles.  The  result 
of  the  vagal  impulses  will  therefore  be  to  increase  the  excitability 
of  the  respiratory  centre  and  make  it  more  susceptible  to  slight  changes 
in  the  carbon  dioxide  tension  of  the  blood,  while  maintaining  a  sufficient 
margin  of  energy  to  meet  the  increased  needs  thrown  on  the  respiratory 
mechanism  by  augmented  metabolism,  such  as  occurs  in  violent 
muscular  exercise. 

The  important  part  played  by  the  vagi  in  the  regulation  of  normal 


REGULATION  OF  RESPIRATORY  MOVEMENTS      1221 

respiration  is  shown  still  more  strikingly  if  the  respiratory  centre 
in  the  medulla  be  separated  from  the  higher  parts  of  the  brain  before 
the  section  of  the  vagi  is  carried  out.  Separation  of  the  medulla 
from  the  higher  parts  of  the  brain,  as  by  section  just  behind  the  corpora 
quadrigemina,  has  practically  no  influence  on  the  respiratory  rhythm. 
If  now  both  vagi  be  divided  the  normal  respiratory  movements  cease 
entirely,  being  replaced  by  a  series  of  inspiratory  spasms,  each  of  which 
lasts  several  seconds  and  is  followed  by  a  pause  of  half  to  one  minute's 
duration.     These  spasms  are  inadequate  for  the  proper  oxygenation 


Rabbit,  3  kilos 

Respirations 
per  minute 

Vol.  of  eacli 
respiration 

Total  ventilation 
per  minute 

Respiration  with  air     . 

,,                 4-2  per  cent.  CO2 . 
„                8-6  per  cent.  CO2. 

air     . 

72 
9G 
97 

72 

c.c. 

19 
25 
29 

20 

1368 
2400 
2813 
1440 

Vagi  Divided 

Respiration  with  air      . 

„                4-2  per  cent.  COg . 
„                 8-6  per  cent.  CO2. 

45 
45 
42 

29 
34 
38 

1305 
1530 
1596 

of  the  blood.  They  become  gradually  less  and  less  frequent,  and  in 
about  half  an  hour  the  animal  dies  of  asphyxia.  We  must  conclude 
therefore  that  the  medullary  respiratory  centre  with  the  help  of  the 
vagi  is  able  to  carry  out  normal  respiratory  movements.  If  both  vagi 
are  cut,  impulses  arrive  at  the  centre  from  the  higher  parts  of  the 
brain  regulating  its  activity,  and  enabling  it  to  carry  out  modified 
but  sufficient  respiratory  movements.  Removed  from  both  these 
sources  of  afferent  impulses,  the  centre  discharges  only  a  series  of  spasms 
which  are  totally  inadequate  for  the  renewal  of  the  blood-gases,  so  that 
the  animal  dies. 

We  may  summarise  these  results  as  follows  : 

Respiratory  centre  ^^'ith  vagi — normal  respiration. 

Respiratory  centre  with  brain — modified  respiration. 

Respiratory  centre  alone — inadequate  spasmotlic  contractions  of 
respiratory  muscles,  and  death  of  animal. 

Tlie  nature  of  the  supplemental  action  of  the  uiid-brain  on  the  medullary 
respiratory  centre  has  not  yet  been  made  out.  It  is  apparently  not  dependent 
on  afferent  impulses  arriving  at  the  brain,  since  section  of  no  cranial  nerve 


1222  PHYSIOLOGY 

affects  in  any  way  the  activity  of  the  centres.  Certain  observers  have  described 
'  accessory  respiratory  centres  '  in  the  mid-brain,  in  the  region  of  the  posterior 
corpora  quadrigemina.  Stimulation  of  this  part  causes  increase  in  the  rate  of 
inspiratory  movements  and  finalh'  tonic  spasm  of  the  diaphragm.  Expiratory 
effects  have  been  produced  by  stimulation  of  the  anterior  corpora  quadrigemina, 
and  it  woiild  seem  that  a  section  has  to  pass  through  or  behind  these  bodies 
in  order  to  produce  the  results,  already  described,  of  cutting  off  the  higher  centres 
from  the  medulla  oblongata  after  division  of  the  vagi.  Other  localised  spots  in 
the  brain  from  which  effects  on  respiration  have  been  obtained  are  the  inner  wall 
of  the  optic  thalamus  and  the  root  of  the  olfactory  tract.  Further  experiments 
are  necessary  before  we  can  regard  any  of  these  centres  as  normally  involved 
in  the  maintenance  or  regulation  of  the  respiratory-  movements. 

APNCEA,  If  artificial  respiration  be  maintained  so  as  to  produce 
a  somewhat  greater  ventilation  than  occurs  by  the  normal  respiratory 
movements  of  the  animal,  a  standstill  of  respiration  is  brought  about. 
This  condition  is  called  apnoea.  The  first  explanation  of  this  standstill 
was  that  it  was  due  to  over- oxygenation  of  the  blood.  The  fact  that 
it  could  be  produced  by  artificial  ventilation  with  inert  gases,  such 
as  hydrogen  and  nitrogen,  as  well  as  the  discovery  of  the  inhibitory 
influence  of  distension  of  the  lungs  on  the  respiratory  centre,  led 
Head  to  ascribe  it  to  the  summation  of  a  series  of  inhibitory  stimuli. 
In  these  experiments,  however,  the  fact  was  forgotten  that  forced 
ventilation  of  the  lungs  with  air  or  any  inert  gases  will  reduce  the 
carbon  dioxide  tension  in  the  blood  circulating  round  the  pulmonary 
alveoli  and  therefore  round  the  respiratory  centre.  A  respiratory 
pause  will  therefore  ensue  and  last  until  the  increasing  accumulation  of 
carbon  dioxide  in  the  blood  raises  its  tension  to  the  normal  height, 
at  which  the  respiratory  centre  is  '  set,'  so  to  speak,  to  respond  by  a 
respiratory  discharge.  If  the  carbon  dioxide  content  of  inspired  air 
be  increased  to  about  4-5  per  cent.,  it  is  impossible  to  produce  an 
apnoeic  pause,  however  rapidly  the  respiratory  movements  be  carried 
out.  It  would  seem  therefore  that  ordinary  apnoea  is  entirely  due 
to  deficiency  of  carbon  dioxide  tension  in  the  respiratory  centre,  and 
that  although  the  vagus  nerve  is  inhibitory  of  respiration,  it  is 
impossible  to  summate  a  series  of  vagus  inhibitions  by  artificial  respira- 
tion so  as  to  produce  a  lasting  cessation  of  respiratory  movements. 
The  chief  use  of  the  vagi  in  respiration  seems  to  be  for  maintaining, 
by  frequent  inhibitions,  the  excitability  of  the  respiratory  centre  at  a 
maximum. 

Miescher  distinguished  tliree  types  of  apnoea,  viz.  : 

Ajmcea  vera,  due  to  the  washing  out  of  COo  from  the  lungs,  and  the  conse- 
quent reduction  of  the  tension  of  this  gas  in  the  blood. 

Apnoea  vagi,  a  stoppage  of  respiration  caused  by  stimulation  of  the  inhibitory 
fibres  of  the  vagi.  This  stoppage  is  limited,  as  we  have  seen,  to  the  immediate 
duration  of  the  stimulus  (whether  electric  or  produced  by  distension  of  the 
lungs). 


REGULATION  OF  RESPIRATORY  MOVEMENTS      1223 

Apnoea  .spuria.  Stoppage  of  respiration  by  stimulation  of  other  nervous  or 
sensory  surfaces.  Tlius  when  a  duck  plunges  there  is  immecljate  stoppage  of 
respiration,  which  may  last  four  or  five  minutes  if  the  animal  remains  so  long 
under  water.  The  same  stoppage  may  be  produced  by  pouring  water  on  the 
beak. 

•  CHEYNE-STOKES  "  BREATHING 
If  a  man  desires  to  hold  his  breath  for  some  time  he  takes 
first  a  series  of  deep  breaths.  The  result  is  to  dimiinsh  the  carbon 
dioxide  tension  in  the  alveoli  and  therefore  to  take  away  the  need 
and  the  desire  to  breathe  until  the  carbon  dioxide  tension  rises 
to  normal  as  the  result  of  the  continued  formation  of  carbon 
dioxide.  By  continuing  forced  respiratory  movements  for  a 
minute     or    two    the    carbon    dioxide    tension    both   in    the    alveoli 


Fig.  .11.'?.     Forced  breathinii  of  air  for  two  minutes,  followed  by  apnfjea  for  two 
minutes,  and  periodic  (' Cheyne- Stokes ')  breathing  for  about  five  minutes. 
At  A,  sample  of  alveolar  air  contained  0.,,  11-44  per  cent.  ;   CO.,,  5-58  per 
cent.     Second  sample  at  b,  0,,  13'55  per  cent.  ;  CO.,,  5-57  per  cent.    (Dottglas 
and  Haldaxe.) 

and  in  the  blood  may  be  brought  down  to  a  very  considerable 
extent.  As  a  result  there  is  a  prolonged  period  of  apnoea.  During 
this  period  of  cessation  of  respirations,  however,  the  oxygen  is  being 
used  up.  and  the  tension  of  this  gas  in  the  alveoli  may  fall  to  such 
an  extent  that  the  respiratory  centre  is  excited  by  lack  of  oxygen 
before  the  carbon  dioxide  tension  in  the  alveoli  has  risen  to  its  normal 
value.  As  a  result  of  the  excitation  by  oxygen  lack,  a  few  breaths 
are  taken  and  the  carbon  dioxide  tension  is  once  more  lowered,  and 
the  stimulation  due  to  the  oxygen  lack,  disappears.  There  is  therefore 
again  a  cessation  of  respiration.  These  periods  of  cessation  alternate 
with  periods  of  respiration  so  that  we  get  a  condition  of  periodic 
breathing  which  is  spoken  of  as  Cheyne-Stokes  respiration.  During 
tlie  period  of  apncBa,  resulting  on  forced  breathing,  the  groat 
diminution  of  oxygen  tension  in  the  alveoli  is  shown  by  the  fact  that 
the  subject  of  the  experiment  becomes  blue,  and  may  indeed  lose 
consciousness.  There  are  at  the  same  time  rhythmic  changes  in  the 
blood  pressure,  which  rises  towards  the  ends  of  the  periods  of  the 
apnoea,  falling  during  the  periods  of  respiration.  The  first  respiration 
after  forced  breathing  is  due  to  oxygen  lack.     The  period  of  apnoea 


1224  PHYSIOLOGY 

may  therefore  be  considerably  prolonged,  if  the  onset  of  oxygen  lack  be 
postponed,  by  increasing  the  tension  of  this  gas  in  the  alveoli  at 
the  commencement  of  the  apnoeic  period.  By  forcibly  breathing  for  a 
period  of  two  minutes  in  an  atmosphere  of  oxygen,  men  have  suc- 
ceeded in  holding  their  breath  for  as  long  a  period  as  eight  minutes 
(Vernon). 

'  Cheyne-Stokes  '  breathing  is  almost  invariably  observed  as  one  of  the  effects 
of  exposure  to  liigh  altitudes,  and  is  then  especially  marked  during  sleep.  It  is 
often  present  when  the  activity  of  the  respiratory  centre  is  depressed,  as  in  cases  of 
uraemia  or  pernicious  anaemia.  Under  these  circumstances  it  may  be  temporarily 
removed  by  administering  either  oxygen  or  carbon  dioxide  (in  small  percentage) 
to  the  patient.  The  oxygen  improves  the  condition  of  tlie  centre ;  the  carbon 
dioxide  acts  as  an  added  stimulus  and  rouses  its  activity. 


SECTION  IV 

THE  EFFECTS  ON  RESPIRATION  OF  CHANGES 
IN  THE  AIR  BREATHED 

We  .  have  already  seen  that  a  moderate  increase  in  the  carbon 
dioxide  percentage  of  the  air  breathed  {e.g.  up  to  4  per  cent.)  causes  a 
])roportional  increase  in  the  ventilation  of  the  lungs  so  as  to  maintain 
the  tension  of  this  gas  in  the  alveoli  at  the  normal  level.  The  same 
effect  is  observed  whether  the  mixture  breathed  contains  18  or  50 
per  cent,  of  oxygen,  showing  that  the  slight  diminution  in  oxygen 
content  caused  by  mixing  the  air  with  carbon  dioxide  is  in  no  way 
responsible  for  the  effect.  If  the  amount  of  carbon  dioxide  be 
increased  to  12  or  15  per  cent,  it  becomes  almost  impossible  to  continue 
the  inhalation  owing  to  the  spasm  of  the  glottis  produced  by  the 
irritant  effects  of  the  carbon  dioxide.  If  these  high  percentages  be 
administered  to  an  animal  by  a  tracheal  tube,  violent  dyspnoea  is 
produced  which  gradually  diminishes,  and  the  animal  passes  into  a 
condition  of  narcosis  in  which  the  respiratory  m,ovements  become  less 
and  the  oxygenation  of  the  blood  is  ineffectively  carried  out  even  in 
the  presence  of  excess  of  oxygen.  The  adm,inistration  of  larger  per- 
centages, such  as  30  or  40  per  cent.,  causes  rapid  death  and  failure  of 
the  circulation  and  respiration,  often  preceded  by  convulsions.  Co- 
incident with  the  increased  respiration  brought  about  by  moderate 
percentages  of  carbon  dioxide  there  is  a  rise  of  blood  pressure,  deter- 
mined partly  by  vascular  constriction,  partly  by  an  increased  output 
from  the  heart.  With  high  percentages  of  carbon  dioxide  the  curve  of 
blood  pressure  obtained  resembles  that  produced  by  lack  of  oxygen. 

Oxygen  itself  exercises  no  excitatory  effects  on  the  respiratory 
movements.  At  the  normal  atmospheric  pressure  the  tension  of  oxy- 
gen in  the  alveoli  is  about  107  mm.  Hg,  a  pressure  which,  as  we  have 
seen,  is  amply  sufficient  to  saturate  the  haemoglobin  passing  through 
the  vessels  of  the  lungs.  Since  the  depth  and  frequency  of  respiration 
are  determined  by  the  carbon  dioxide  tension  in  the  alveoli  no  alteration 
in  respiration  will  be  produced  by  increasing  the  tension  of  oxygen  in 
the  air  breathed  above  its  normal  amount.  The  respiratory  move- 
ments in  an  atmosphere  of  pure  oxygen  will,  in  the  normal  individual, 
remain  unchanged. 

This   Btatc'inent  is  only  true  for  tiic  healtliy  individual.     If    from  failure  of 
the  heart  and  circulation,  or  diminished  oxygen  tension,  or  severe  loss  of  blood, 

1225 


1226  PHYSIOLOGY 

the  oxygenation  of  the  blood  is  already  insufficient,  marked  amelioration  of  the 
symptoms  may  be  produced  by  inhalation  of  piue  oxygen.  Especially  is 
this  noticeable  where  there  is  failui'e  of  the  heart.  In  these  cases  the  heart, 
already  affected,  is  unable  to  keep  up  an  adequate  circulation  and  to  supply  itself 
with  sufficient  oxygen.  A  vicious  circle  is  thus  established  in  which  the  heart 
tends  to  get  steadily  worse.  By  admmistration  of  oxygen  an  adequate  supply 
of  this  gas  to  the  heart-muscle  is  assm'cd  ;  the  heart-beat  therefore  becomes  more 
effective  and  the  whole  circulation  is  improved  and  therewith  the  provision  of 
oxygen  to  the  body  at  large. 

If  a  warm-blooded  animal  be  immersed  in  a  chamber  and  sub- 
mitted to  pure  oxygen  at  a  pressure  of  four  atmospheres,  it  dies  as 
rapidly  as  if  it  were  in  an  atmosphere  of  pure  nitrogen.  At  this  pressure 
the  oxidative  processes  of  the  body  as  well  as  the  intake  of  oxygen  into 
the  lungs  are  absolutely  abolished.  It  is  interesting  to  note  that  certain 
other  oxidative  phenomena,  e.g.  the  spontaneous  oxidation  of  phos- 
phorus, also  cease  if  the  tension  of  the  oxygen  be  sufficiently  high. 
Exposure  of  an  animal  over  a  considerable  period  of  time  to  a  pressure 
of  oxygen  of  two  atmospheres  may,  as  Haldane  and  Lorraine  Smith 
have  shown,  set  up  severe  inflammation  of  the  lungs  and  thereby  cause 
death  indirectly. 

CHANGES  IN  TENSION  OF  OXYGEN.  If  a  man  breathe  a  mixture 
of  nitrogen  and  oxygen  free  from  carbon  dioxide,  and  the  oxygen  be 
gradually  diminished,  no  feeling  of  '  want  of  breath  '  may  be  ex- 
perienced. With  percentages  of  oxygen  as  low  as  12  per  cent,  there  may 
be  no  change  in  the  breathing,  even  though  the  deficient  oxygenation 
of  the  blood  may  be  shown  by  the  blueness  of  the  lips  and  face.  If  the 
oxygen  be  reduced  still  lower,  a  certain  amount  of  hyperpnoea  may 
occur,  but  in  many  cases  the  individual  experimented  on  may  not  feel 
any  ill  effects  until  he  suddenly  becomes  unconscious  from  lack  of 
oxygen.  If  fresh  oxygen  be  not  supplied  this  unconsciousness  may 
be  followed  by  convulsive  movements  and  death.  If  the  administra- 
tion of  low  percentages  of  oxygen,  e.g.  about  10  to  12  per  cent,  of  an 
atmosphere,  be  continued  for  some  time,  the  subject  of  the  experi- 
ment may  suffer  considerable  discomfort.  One  of  the  signs  of  oxygen 
lack  is  often  severe  headache,  and  this  may  be  accompanied  by  vomit- 
ing or  nausea  and  by  a  feeling  of  discomfort  in  the  precordial  region. 
Many  experiments  have  been  made  both  on  animals  and  man  by 
submitting  them  to  a  lowered  atmospheric  pressure  in  chambers 
specially  built  for  the  purpose.  The  limit  to  which  the  pressure  may 
be  reduced  varies  in  different  individuals,  the  variations  being  deter- 
mined by  the  type  of  respiratory  movement  of  the  individual  in 
question,  since  on  the  depth  of  respiration  depends  the  relation 
between  the  tension  of  oxygen  in  the  alveoli  and  that  in  the  inspired 
air.  The  lowest  limit  at  which  life  is  possible  corresponds  to  an  oxygen 
tension  in  the  alveoli  of  27  to  30  mm.  Hg. 


EFFECTS  OF  CHANGES  IN  AIR  BREATHED 


122' 


MOUNTAIN  SICKNESS.  The  phenomena  just  described  as  en- 
suing; on  exposure  of  an  animal  to  low  oxygen  tensions  iji  a  respiratory 
chamber  for  some  length  of  time  are  exactly  similar  to  those  which 
are  regarded  as  characteristic  of  mountain  sickness.  The  following 
tal)le  shows  the  diminution  in  the  atmospheric  pressure  at  varying 
hciuhts  above  tlie  level  of  the  sea  : 


Height  above  sea 

Barometer 

I'er  cent,  of  an 

level,  in  metres 

mm.  Ug 

atmosphere 

0 

760 

100 

1000 

670 

88 

2000 

593 

78 

3000 

524 

69 

4000 

463 

61 

5000 

410 

54 

6000 

357 

47 

7000 

320 

42 

At  a  height  of  5000  metres  the  pressure  of  the  air  is  reduced  to 
little  over  half  an  atmosphere  and  the  oxygen  tension  is  therefore  only 
about  11  per  cent,  of  an  atmosphere.  It  must  be  remembered  that  in 
most  cases  of  mountain  sickness,  in  addition  to  this  absolute  oxygen 
lack,  there  is  increased  consumption  of  oxygen,  owing  to  the  muscular 
exercise  involved  in  climbing.  Moreover  a  greater  volume  of  the  alveolar 
air  must  consist  of  carbon  dioxide  if  the  tension  of  this  gas  is  to  be 
kept  constant  (cp.  Fig.  504,  p.  1207).  Since  diminished  oxygen  tension, 
within  fairly  wide  limits,  does  not  excite  any  corresponding  increase 
in  the  respiratory  movements,  there  must,  at  these  heights,  be  an 
actual  diminution  in  the  oxygen  tension  in  the  alveoli.  This  diminu- 
tion in  tension  is  shown  by  a  series  of  observations  carried  out  by 
Zuntz  on  himself  and  fellow  workers  at  different  localities.  It  may  be 
noted  that  on  Monte  Rosa,  where  the  oxygen  tension  in  the  alveoli  was 
reduced  to  between  37  and  57  mm.  Hg,  as  against  the  normal  101 
to  105  mm.  Hg,  all  t)ie  members  of  the  party  were  suffering  from 
mountain  sickness. 


Ucight 

Alveolar  C 

,  tension 

above  sea 

Os  tension 

level, 

of  air 

metres 

A 

B. 

c 

1) 

E 

1 

Hi^rVin 

54 

157 

105 

101 

_ 

105 

103 

104 

Biit'iiz 

500 

148 

84-5 

94 

80 

88 

86 

ni 

JiricnztT  Rot  horn 

213(1 

121 

68 

66 

64 

62 

66 

71 

Col  d'Ok-n 

2!t()0 

110 

57 

— 

— 

60 

68 

68 

Monte  Rosa 

4500 

89 

— 

46 

49 

61 

37 

57 

1228  PHYSIOLOGY 

As  a  result  of  the  oxygen  starvation  there  is  inadequate  supply 
of  this  gas  to  the  heart,  so  that  the  circulation  tends  to  fail,  especially 
on  making  the  slightest  muscular  movements.  At  the  same  time 
the  oxygen  starvation  of  the  brain  produces  failure  of  judgment  and 
inability  to  carry  out  or  to  co-ordinate  muscular  movements  properly. 
The  symptoms  as  a  rule  do  not  increase  until  death  results,  so 
that,  although  there  is  an  oxygen  starvation  of  the  body,  there  must 
be  some  means  by  which  the  respiration  is  modified  so  as  to  obtain  a 
sufl&ciency  of  this  gas  for  the  lowered  requirements  of  the  body.  That 
the  adaptation  is  effective  is  shown  by  the  fact  that  most  individuals, 
if  they  remain  at  a  height,  gradually  recover  from  the  mountain 
sickness  and  may  finally  be  able  to  carry  out  muscular  movements  with 
almost  as  great  precision  and  force  as  they  could  previously  on  the 
plains.  The  mechanism  by  which  increased  ventilation  of  the  lungs 
is  attained  is  that  already  mentioned  in  dealing  with  the  effects  of 
lack  of  oxygen,  namely,  the  production  of  acid  substances  in  the  body. 
The  respiratory  centre  is  thus  stimulated  by  these  acid  substances, 
especially  lactic  acid,  as  well  as  by  the  carbon  dioxide  tension  of  the 
blood,  and  the  joint  action  of  these  two  substances  (which  probably 
co-operate  in  raising  the  hydrion  concentration  of  the  blood)  deter- 
mines the  marked  increase  in  the  lung  ventilation.  Since  the  carbon 
dioxide  is  no  longer  the  sole  factor  responsible  for  the  ventilation, 
the  tension  of  this  gas  in  the  alveolar  air  is  diminished. 

ACAPNIA.  This  diminution  of  carbon  dioxide  tension  in  the  blood  and  alveolar 
air  has  been  regarded  by  Mosso  as  the  essential  factor  in  the  causation  of  mountain 
sickness  and  has  been  designated  acapnia.  It  may  be  absent,  however,  in  the  most 
marked  cases  of  momitain  sickness,  where  the  respiratory  centre  has  failed  to 
respond  to  the  additional  acid  stimulation,  and  may  be  present  to  a  marked 
degree  in  individuals  who  are  experiencing  none  of  the  ill  effects  of  this 
disorder. 

Another  important  means  of  rapid  adaptation  is  by  means  of  the 
circulation.  This  is  noticeable  even  in  the  case  of  persons  sitting 
quietly  in  a  gas  chamber  who  are  subjected  to  gradually  low^er  pressures. 
It  is  evident  that  a  deficient  passage  of  oxygen  from  the  alveoli  to  the 
blood  may,  so  far  as  the  tissues  and  heart  are  concerned,  be  accom- 
modated for  by  increasing  the  rapidity  of  the  circulation,  and  this 
is  eSected  by  a  quickening  of  the  pulse-rate.  The  following  Table 
shows  the  changes  in  the  .pulse- rate  caused  by  exposure  to  varying 
pressures  in  a  gas  chamber  : 


Pulse  in  Gas  Chamber 

Pressure 

Pulse 

720 

64 

650 

72 

424 

. 

84 

EFFECTS  OF  CHANGES  IN"  AIR  BREATHED 


1229 


This  quickening  of  the  pulse  is  to  be  observed  also  in  the  trained 
mountain  soldier,  in  individuals  in  whom  there  is  no  lowering  of  the 
alveolar  carbon  dioxide  tension,  so  that  apparently  in  such  cases 
the  whole  adaptation  to  altered  conditions  is  by  means  of  the  circula- 
tion. In  cases  where  adaptation  fails  it  is  in  the  circulation  that 
the  failure  is  most  marked,  so  that  the  symptoms  of  severe  mountain 
sickness  resemble  closely  those  produced  by  rapid  heart-failure. 
Dilated  heart,  cyanosis,  muscular  weakness,  vomiting,  mental  torpor, 
inco-ordination,  delirium,  may  all  be  observed  in  both  cases.  The 
disturbance  of  the  central  nervous  system  is  showTi  by  the  almost 
invariable  occurrence  at  great  heights  of  Cheyne-Stokes  breathing. 

If  the  animal  is  able  to  withstand  the  immediate  effects  of 
exposure  to  a  rarefied  atmosphere,  a  process  of  adaptation  comes  into 
play  which  finally  fits  him  for  discharging  his  functions  normally  even 
at  the  high  altitude.  From  the  lack  of  sensibility  of  the  respiratory 
centre  to  small  changes  in  oxygen  tension,  any  diminution  in  oxygen 
tension  must  cause  a  corresponding  diminution  in  the  degree  of  satura- 
tion of  the  hgemoglobin  of  the  blood.  This  change  in  oxygen  satura- 
tion is  at  once  felt  by  the  blood-forming  organs.  As  an  immediate  effect 
of  change  to  a  region  of  low  atmospheric  pressure  there  is  a  relative 
increase  in  the  blood-corpuscles  due  to  a  concentration  of  the  blood 
and  a  diminution  of  its  plasma.  Simultaneously,  however,  the  blood- 
forming  organs  enter  into  a  condition  of  increased  activity,  so  that  after 
a  stay  of  four  or  five  weeks'  duration  at  a  height  both  corpuscles  and 
haemoglobin  are  considerably  increased  in  total  amount.  The  following 
Table  shows  the  average  number  of  red  corpuscles  contained  in  one 
cubic  millimetre  of  blood  from  the  inhabitants  of  regions  at  varyino^ 
altitudes  : 


Height  above  sea 

level, 

Red  corpuscles 

metres 

Christiania    . 

0 

4,970,000 

Zurich . 

412 

5,752,000 

Davos 

1560 

6,551,000 

Arosa  . 

1800 

7,000.000 

Cordilleras    . 

4392 

8.000,000 

There  is  of  course  a  limit  to  the  power  of  adaptation,  a  limit  which 
varies  in  different  individuals.  Thus  for  some  men  it  is  impossible 
to  stay  any  length  of  time  in  the  high  settlements  in  the  Andes,  while 
others,  after  two  or  three  weeks'  discomfort,  become  perfectly  inured 
to  their  new  conditions.  It  seems  doubtful,  however,  whether  any 
of  the  present  race  of  men  could  become  adapted  to  permanent  residence 


1230  PHYSIOLOGY 

at  a  height  over  5000  metres,  and  though  for  a  certain  length  of  time 
by  bringing  into  play  the  reserve  mechanisms  already  described, 
they  may  raise  themselves  to  a  height  considerably  above  5000  metres, 
it  seems  questionable  whether  without  artificial  means,  such  as  the 
inhalation  of  oxygen,  it  will  be  possible  for  any  man  to  attain  the 
highest  points  on  the  earth's  surface,  or  at  any  rate  to  arrive  there  by  his 
own  unaided  efforts.  The  highest  summits  in  the  Himalayas  have  a 
height  approaching  that  attained  by  Tissandier  with  his  two  com- 
panions in  his  famous  balloon  ascent,  namely,  8600  metres.  In  this 
ascent,  although  oxygen  inhalation  was  used  (somewhat  ineffectively), 
two  of  the  party  succumbed. 

The  stimulating  effect  of  oxygen  lack  on  the  blood-forming  organs 
extends  also  to  the  muscular  system,  so  that  one  of  the  effects  of  a 
residence  in  high  altitudes  is  increased  assimilation  of  nitrogen.  For 
a  time  the  nitrogen  output  is  less  than  the  nitrogen  intake,  and  there 
is  an  actual  building  up  of  new  tissue.  The  condition  of  the  indi- 
vidual is  similar  to  that  of  a  growing  animal,  a  fact  which  may  explain 
the  admirable  results  of  a  mountain  holiday.  We  can  hardly  im- 
agine that  the  power  of  the  organism  to  react  in  this  way  was  evolved 
through  generations  of  mountain  climbing.  We  are  probably  here 
making  use  of  an  adaptation  which  has  been  evolved  for  the  purpose 
of  retrieving  loss  of  blood  by  hsemorrhage,  such  as  must  have  been  of 
continual  occurrence  in  the  struggle  of  individual  against  individual, 
which  has  resulted  in  the  survival  of  the  animals  of  to-day. 

ALTERATIONS  IN  THE  NITROGEN  TENSION.  The  nitrogen 
of  the  atmosphere  plays  no  part  in  the  metabolism  of  the  body,  and 
must  be  regarded  as  a  purely  inert  gas.  It  is  a  matter  of  indifference 
whether  under  normal  atmospheric  pressure  we  breathe  an  atmosphere 
of  pure  oxygen  or  one  containing  one-fifth  part  of  this  gas  diluted 
with  four-fifths  of  nitrogen.  The  very  inertness  of  nitrogen  may  be 
of  danger  to  the  body  under  certain  conditions.  If  a  man  or  an 
animal  be  exposed,  as  in  a  diving-bell,  to  a  pressure  of  three,  four,  or 
six  atmospheres,  the  respiratory  functions  are  unaffected,  but  the 
amount  of  nitrogen  dissolved  in  the  fluids  of  the  body  is  increased  in 
direct  proportion  to  the  pressure.  If  the  pressure  be  now  suddenly 
released,  the  nitrogen,  which  cannot  be  used  up  by  the  tissues,  is  given 
off  from  the  body-fluids  in  the  form  of  bubbles,  just  as  carbonic  acid 
gas  rises  in  bubbles  from  soda-water  when  the  pressure  is  removed  by 
withdrawing  the  cork  from  the  bottle.  These  bubbles  occurring 
in  all  the  capillaries  obstruct  the  flow  of  blood,  and  therefore,  if  the 
evolution  of  gas  is  sufficiently  large,  the  animal  dies  in  convulsions. 
A  similar  evolution  of  gas  may  occur  in  the  spinal  cord,  giving  rise  to 
destruction  of  the  cord  and  paralysis  ('  divers'  palsy  ').  In  order  to 
prevent  this  sudden  evolution  of  gas  it  is  necessary  that  the  change 


EFFECTS  OF  CHANGES  IN  AIR  BREATHED  1231 

from  the  high  pressure  to  the  ordinary  atmospheric  pressure  should 
be  carried  out  gradually,  so  as  to  give  the  blood-plasma,  supersaturated 
with  nitrogen,  time  to  get  rid  of  its  excess  of  nitrogen  without  the  forma- 
tion of  bubl)l('S. 

OTHER  GASES.  Hydrogen  and  methane  are,  like  nitrogen,  in- 
different gases.  They  may  be  respired  if  mixed  with  20  per  cent,  of 
oxygen,  and  either  of  the  gases  may  be  used  instead  of  nitrogen  to 
dilute  the  oxygen  that  we  breathe,  without  harm  or  inconvenience. 

Carbon  monoxide  is  rapidly  poisonous  by  its  action  on  the  red 
corpuscles.  It  combines  with  haemoglobin,  forming  CO-hsemoglobin, 
a  compound  which  is  much  more  stable  than  oxyhsemoglobin.  The 
blood  is  therefore  deprived  of  its  oxygen  carrier,  and  the  animal  dies  of 
asphyxia.  We  have  seen,  however,  that  the  displacement  of  oxygen 
by  CO  is  not  absolute,  but  only  relative.  Hence,  although  the  avidity 
of  CO  for  hsemoglobin  is  140  times  that  of  oxygen,  we  can  convert  the 
CO  back  into  oxyhsemoglobin  by  increasing  the  mass  influence  of  the 
oxygen.  This  may  be  done  by  giving  the  poisoned  animal  pure 
oxygen  to  breathe,  or  even  oxygen  under  pressure.  In  pure  oxygen 
at  a  pressure  of  two  atmospheres  an  animal  can  breathe  and  live,  even 
though  the  whole  of  its  hsemoglobin  is  converted  into  CO-haemoglobin, 
the  amount  of  oxygen  which  is  simply  dissolved  by  the  blood-plasma 
being  sufficient  at  this  pressure  for  the  respiratory  needs  of  the  animal 
(Haldane). 

Other  gases  which  have  special  poisonous  properties  are  hydro- 
cyanic acid,  sulphuretted  hydrogen,  phosphuretted  hydrogen  (PHg), 
arseniuretted  hydro gcMi,  &c. 

IRRESPIRABLE  GASES  are  those  which  are  so  irritating  that 
they  produce  spasm  of  the  glottis.  Such  are  ammonia,  chlorine^ 
sulphur  dioxide,  nitric  oxide,  and  many  others. 

VENTILATION 

A  point  of  practical  importance  is  the  securing  to  each  individual 
of  sufficient  fresh  air,  so  that  he  may  always  have  a  plentiful  supplv 
of  oxygen,  and  may  be  relieved  of  his  waste  products.  It  is  found  that 
a  dwelling-room  becomes  unpleasant  and  stuffy  when  the  percentage 
amount  of  COg  has  reached  0-1  per  cent.  This  stuffiness  is  supposed 
to  be  due  to  organic  exhalations  from  the  skin,  lungs,  and  alimentarv 
canal,  some  of  which  have  a  poisonous  effect,  giving  rise  to  headache 
and  sleepiness.  Since  these  cannot  be  measured,  it  is  taken  as  a 
casdinal  rule  in  ventilation  that  the  amount  of  CO2  should  never  rise 
above  0-1  per  cent. 

Since  in  questions  of  ventilation  we  have  generally  to  deal  with 
trades  in  which  the  metric  measure  is  not  used,  it  raav  be  convenient 


1232  PHYSIOLOGY 

to  give  the  data  as  to  carbon  dioxide  production  and  the  amount  of 
air  required  in  cubic  feet. 

An  adult  man  gives  ofi  about  0-6  cubic  foot  of  COg  every  hour. 
Hence  in  that  time  he  raises  the  amount  of  COg  in  1000  cubic  feet  of 
air  from  '04  per  cent,  (the  normal  amount  in  the  atmosphere)  to 
0-1  per  cent.  He  must  therefore  be  supplied  with  2000  cubic  feet  of 
air  per  hour  in  order  to  keep  the  amount  of  COg  down  to  -07  per  cent. 

(Ordinary  air  contains  -04  per  cent.  COg,  therefore  2000  cubic  feet 
would  contain  0-8  cubic  foot  COg,  which  with  the  0-6  cubic  foot  given 
off  by  the  man  would  be  1-4,  which  is  -07  per  cent.) 

In  order  that  the  air  may  be  easily  renewed  without  giving  rise 
to  excessive  draught,  a  certain  amount  of  cubic  space  must  be  allotted 
to  each  man.  Each  adult  should  have  in  a  room  1000  cubic  feet  of 
space,  and  be  supplied  every  hour  with  2000  to  3000  cubic  feet  of  air. 


SECTION  V 

THE  MECHANISMS  OF  OXIDATION   IN  THE 
TISSUES 

The    blood    in   its   passage   tlirough   tlie  capillaries  takes  up  carbon 
dioxide    from  the  tissues,  giving  oxygen  to  the  latter  in  exchange. 
This  interchange  is  determined  by  the  differences  in  tension  of   the 
gases  on  the  two  sides  of  the  capillary  wall.     Whereas  the  tension  of 
oxygen  in  the  plasma  varies  from  100  mm.  Hg  in  arterial  to  25  mm. 
Hg  in  venous  blood,  the  tension  of  oxygen  in  the  tissues  outside  the 
vessels  in  most  cases  approaches  0,  as  is  shown  by  Ehrlich's  methylene- 
blue  experiment  described  on  p.  1186.     On  the  other  hand,  the  ten- 
sion of  carbon  dioxide  in  the  tissues,  as  judged  from  the  examination 
of  fluids  such  as  bile  and  urine,  varies  from  6  to  10  per  cent,  of  an 
atmosphere.      The  continuous  flow  of  oxygen  into,  and  of  carbon 
dioxide  away  from,  the  tissues  points  to  the  constant  occurrence  of 
oxidative  changes  in  the  tissue-cells.     By  the  blood  the  tissues  receive 
not  only  oxygen  but  also  food-stuft's,  namely,  proteins  or  amino-acids, 
fats,  and  sugars,  derived  from  the  alimentary  canal,  or,  in  starvation, 
from  other  parts  of  the  body.     The  activity  of  the  tissues,  whether 
motor,  as  in  the  case  of  muscle,  or  secretory,  as  in  the  case  of  glands,  is 
derived  from  the  energy  set  free  in  the  partial  or  complete  oxidation 
of  these  food-stuffs,  which  occurs  within  the  active  cells  themselves. 
A  study  of  the  mechanism  of  oxidation  in  the  body  involves  there- 
fore a  consideration  of  the  processes  which  take  place  within  the  con- 
fines of  each  cell.     The  question  is  by  no  means  an  easy  one.     Although 
we  speak  of  the  '  burning '  of  food-stuffs,  and  compare  the  processes 
in  the  body  to  those  which  take  place  in  combustion,  e.g.  in  a  candle- 
flame,  the  analogy  is  after  all  a  very  rough  one.     In  the  first  place, 
the  food-stuffs,  even  after  absorption,  belong  to  a  class  of  substances 
which  have  been  designated  as  dysoxidisable,  since  they  present  no 
tendency    to    combine    with    ordinary    atmospheric    oxygen.     Thus 
sugars,  i)roteins,  or  fats,  if  kept  free  from  microbial  mfection,  may  be 
kept  for  years  exposed  to  the  air  without  undergoing  any  change.    It  is 
true  that  in  certain  eases,  e.g.  in  alkaline  solutions  of  sugar,  we  may 
obtain  slow  absorption  of  oxygen  and  oxidation  of  the  sugar.     The 
changes  are,  however,  slight  and  limited  in  extent.     All  these  food- 
stuffs are  susceptible  of  combustion   if  raised   to  a   sufficiently  high 

1233  78 


1234  PHYSIOLOGY 

temperature,  but  in  the  animal  body  the  processes  of  oxidation  have 
to  go  on  at  a  temperature  varying  between  5°  and  40°  C,  and  in  a 
solution  which  is  almost  neutral  in  reaction.  It  might  be  said  that 
at  the  temperature  of  an  ordinary  flame  the  combustion  of  the  food- 
stuffs is  immediate  and  complete,  whereas  in  the  body  the  oxidation 
takes  place  by  stages,  Eecent  research  has  tended  to  remove  this 
point  of  distinction  by  pointing  out  that  even  in  an  explosion  of  a 
mixture  of  methane  and  oxygen  there  is  a  series  of  intermediary 
products,  and  that  the  whole  process,  if  analysed,  is  made  up  of  stages 
in  which  hydrolysis  and  oxidation  go  on  simultaneously,  so  that 
on  this  account  it  is  difficult  to  cause  a  combination,  even  of  hydrogen 
and  oxygen,  in  the  complete  absence  of  any  watery  vapour.  The 
oxidations  in  the  body  are  strictly  limited  both  in  nature  and  extent. 
The  mere  fact  that  a  substance  is  readily  or  even  spontaneously 
oxidisable  [autoxidisahle)  affords  no  guarantee  that  it  will  undergo 
oxidation  in  the  animal  body.  Thus  phosphorus  or  pyrogallol  taken 
by  the  mouth  can  be  recovered  in  an  unoxidised  form  from  the  urine. 
Carbon  monoxide  is  excreted  unchanged.  There  must  apparently  be 
some  definite  relationship  between  the  molecular  structure  of  the  food- 
stuff and  that  of  the  cells  of  the  body.  Thus  ordinary  proteins  which 
undergo  complete  oxidation  contain  large  quantities  of  leucine.  This 
substance  is  Isevorotatory  and  is  designated  Z-leucine.  If  Z-leucine 
be  administered  to  rabbits  it  is  completely  oxidised.  If  its  isomer 
(Z-leucine,  resembling  it  in  every  particular  so  far  as  we  can  see  except 
in  its  relation  to  polarised  light,  be  administered  to  a  rabbit,  the  greater 
part  of  the  substance  passes  through  the  body  unchanged.  In  the 
same  way  there  are  sixteen  sugars  of  the  formula  CgHjaOe.  Of  these 
only  four,  namely,  glucose,  fructose,  galactose,  and  mannose,  can  be 
oxidised  in  the  animal  body.  Other  sugars  differing  in  so  slight  a 
degree  from  these  four  as,  e.g.,  ^glucose  or  Z-fructose,  cannot  be 
utilised  by  the  body.  Not  only  must  there  be  a  distinct  relation 
between  the  structure  of  the  cell  and  the  molecular  structure  of  the 
food-stuff  supplied,  but  there  must  be  different  mechanisms  for  the 
food-stuffs  and  their  derivatives.  Thus  in  certain  cases  of  disease  or 
of  abnormal  nutrition  the  body  may  lose  absolutely  the  power  of 
utilising,  i.e.  of  oxidising,  a  whole  class  of  food-stuffs.  In  severe 
diabetes,  or  after  destruction  of  the  pancreas,  glucose  behaves  in  the 
body  as  if  it  were  one  of  the  artificial  unassimilable  sugars.  The 
normal  oxidation  of  fats  piobably  proceeds  by  stages  in  each  of  which 
two  atoms  of  carbon  undergo  oxidation.  The  penultimate  stage  in 
the  oxidation  of  any  of  the  higher  fatty  acids  is  thus  oxybutyria  acid. 
In  complete  carbohydrate  starvation,  for  some  reason  or  other,  the 
body  loses  its  power  of  completing  this  last  stage,  so  that  the  oxy- 
butyric  acid  undergoes  no  further  oxidation,  and  either  accumulates 


MECHANISMS  OF  OXIDATION  IN  TISSUES  1235 

in  the  body  or  is  excreted  combined  with  bases  in  the  urine.  In  the 
normal  individual  tyi'osine,  whether  administered  separately  or  in 
combination  in  protein,  is  completely  oxidised,  the  benzene  ring  being 
broken  up.  In  certain  rare  cases  of  disordered  metabolism  the 
patient,  who  is  otherwise  apparently  well,  is  unable  to  effect  the  total 
oxidation  of  tyrosine,  which  is  therefore  excreted  as  homogentisic  acid, 
after  undergoing  only  the  first  stage  of  its  normal  transformation  in  the 
body.  These  various  mechanisms  are  adjusted  in  each  case  to  the 
functional  activity  of  the  cell  and  are  limited  therefore,  not  by  the 
supply  of  oxygen  or  of  food-stulf  to  be  oxidised,  but  by  the  necessities 
of  the  cell,  i.e.  the  adaptations  induced  in  it  by  its  environmental 
changes.  In  discussing  the  mechanism  of  intracellular  oxidation  we 
have  therefore  to  consider  in  the  first  place  how  the  dysoxidisable 
food-stufEs  are  made  to  combine  with  the  molecular  oxygen  diffusing 
into  the  cells  from  the  blood  in  the  capillaries,  and  in  the  second  place 
the  means  by  which  these  oxidative  changes  are  strictly  limited  in 
accordance  with  the  necessities  of  the  cell,  and  finally  the  nature  of 
the  specific  oxidative  mechanisms  for  each  kind  of  food-stuff  and  for 
the  various  stages  in  the  oxidation  of  each  food-stuff. 

We  are  very  far  as  yet  from  being  able  to  give  a  definite  answer 
to  any  one  of  these  questions.  Even  in  the  fiist  problem,  namely,  the 
oxidation  of  dysoxidisable  substances,  we  have  to  confine  ourselves 
almost  exclusively  to  speculation  on  possibilities.  Although  these 
substances  will  not  unite  mth  the  oxygen  of  the  air,  in  which  the  com- 
bining activities  of  the  oxygen  are  satisfied  by  the  combination  of 
two  atoms  to  form  one  molecule,  many  of  them  readily  undergo 
oxidation  if  subjected  to  the  action  of  '  atomic  '  oxygen  or  '  active  ' 
oxygen,  and  it  has  been  suggested  that  the  problem  of  the  oxidation 
of  the  body  is  really  bound  up  with  the  question  as  to  the  mode  of 
activation  of  the  molecular  oxygen  derived  from  the  oxyhaemoglobin. 
Thus  Hoppe-Seyler  suggested  that  the  activation  of  oxygen  might 
occur  through  the  intermediation  of  reducing  substances.  He  sup- 
posed that  reducing  substances  might  be  formed  under  the  influence 
of  ferments  by  hydrolytic  splitting  of  the  food-stuff's.  A  reducing 
substance  is  one  that  has  sufficient  affinity  for  oxygen  at  the  ordinary 
temperature  to  tear  asunder  the  bonds  which  unite  two  atoms  of 
oxygen  to  form  one  molecule,  and  to  combine  with  one  or  both  of  the 
atoms  so  set  free.  If  the  combination  is  with  only  one  atom,  the 
other  atom  of  the  oxygen  molecule  is  set  free  in  an  active  form,  and 
is  therefore  able  to  oxidise  dysoxidisable  substances  which  may  be 
present.  Thus,  when  a  mixture  of  ammonia  and  pyrogallol  is  ex- 
posed to  the  atmosphere,  the  oxygen  is  rapidly  absorbed,  forming  a 
dark  brown  solution,  pyrogallol  being  therefore  a  reducing  agent.  But 
at  the  same  time  a  certain  amount  of  the  ammonia  (a  dysoxidisable 


1236  PHYSIOLOGY 

substance)  undergoes  oxidation  with  the  formation  of  nitrite.  In  the 
slow  spontaneous  oxidation  of  phosphorus  w^hich  occurs  on  exposing 
this  substance  to  the  atmosphere,  ozone,  OgO,  is  always  formed.  As 
a  type  of  the  formation  of  reducing  substances  in  hydrolytic  fermenta- 
tions may  be  adduced  the  butyric  acid  fermentation,  in  which  sugar 
is  converted  into  butyric  acid,  carbonic  acid,  and  hydrogen  : 

CeHi^Oe  -  C^HsOa  +  200^  +  SH^. 

The  hydroge:!  produced  in  this  process  would  act  as  a  reducing  agent. 
There  is  no  doubt  that  reducing  substances  are  formed  under  normal 
circumstances  in  the  tissues,  as  is  shown  by  the  methylene-blue 
experiment,  and  it  is  possible  that  such  reducing  substances  may  aid 
in  activating  oxygen  and  in  the  induction  of  certain  oxidative  processes. 
The  activation  of  oxygen  would,  however,  not  explain  the  specific 
character  of  the  various  oxidations,  and  the  accurate  gxadation  of  these 
oxidations  to  the  necessities  of  the  cell.  In  many  cases  reducing  sub- 
stances may  themselves  act  as  carriers  of  oxygen,  and  their  action  be 
more  or  less  specific.  If,  for  instance,  glucose  be  boiled  with  an  am- 
moniacal  sohition  of  cupric  hydrate,  it  undergoes  oxidation,  the  cupric 
being  reduced  to  cuprous  hydrate.  Cuprous  hydrate  in  ammoniacal 
solution  is  a  reducing  substance  ;  it  absorbs  oxygen  from  the  air  and 
is  reconverted  to  cupric  hydrate.  A  small  amount  of  cupric  hydrate 
therefore,  in  the  presence  of  air,  may  act  as  a  carrier  of  oxygen  from 
the  air  to  the  sugar  and  may  thus  oxidise  indefinitely  large  quantities 
of  sugar.  In  the  same  way,  if  indigo  in  alkaline  solution  be  boiled 
with  sugar,  it  undergoes  reduction  with  the  formation  of  a  colourless 
compound.  On  shaking  the  decolorised  solution  with  air  it  absorbs 
oxygen  with  the  reproduction  of  indigo,  so  that  here  again  minute  quan- 
tities of  indigo  blue  may  serve  to  oxidise  large  quantities  of  glucose. 
The  mode  of  action  of  these  oxygen  carriers  resembles  closely  that  of 
the  various  ferments  which  effect  the  transference  of  water  from  the 
menstrum  to  the  substrate  [e.g.  trypsin,  invertase,  &c.).  These 
hydrolytic  ferments  differ  from  ordinary  hydrolytic  agents,  such  as 
dilute  acids,  in  the  specific  character  of  their  action.  Trypsin,  for 
instance,  will  hydrolyse  polypeptides  of  a  type  corresponding  to 
those  which  make  up  the  ordinary  food- products,  but  is  powerless  to 
hydrolyse  polypeptides  composed  of  artificial  amino-acids  which  are 
the  optical  isomers  of  those  occurring  in  the  body.  It  seems  possible 
that  we  might  explain  the  specific  oxidations  occurring  in  the  cell  by 
assuming  the  presence  of  a  immber  of  ferments,  oxidases,  which  would 
act  as  oxygen  carriers,  but  each  of  which  would  only  be  able  to  act  on 
a  certain  type  of  food-stuff  or  on  molecules  of  a  given  configuration. 

Such  oxidative  ferments  have  been  described  as  existing  in  many 
animal   and   vegetable   extracts.     Many   species   of   fungus   contain 


MECHANISMS  OF  OXIDATION  IN  TISSUES  1237 

a  ferment  known  as  tyrosinase,  from  the  fact  that,  when  added  to 
solutions  of  tjTOsine  in  the  presence  of  air,  the  tyrosine  is  oxidised  with 
the  formation  of  a  brown  pigment.  The  same  ferment  is  able  to  effect 
the  oxidation  of  other  aromatic  substances.  The  browning  of  a 
freshly  cut  potato  or  apple  on  exposure  to  the  air  is  similarly  ascr  bed 
to  the  oxidation  of  a  chromogen  by  the  oxygen  of  the  air,  through  the 
intermediation  of  an  oxidase  present  in  the  cells.  If  benzyl  alcohol  or 
salicyl  aldehyde  be  added  to  a  suspension  of  liver-cells  in  blood,  and 
air  be  allowed  to  bubble  through  the  mixture  for  some  time,  the  alcohol 
or  aldehyde  is  found  to  have  been  oxidised  to  the  corresponding  acid. 
In  the  same  way  xanthine  (C5H4N4O2)  added  to- a  mixture  of  spleen 
pulp  and  defibrinated  blood  is  converted  into  uric  acid  (C5H4N403). 

Bach  and  Chodat  have  shown  that  in  many  cases  the  oxidase  is  not 
a  single  substance,  but  a  mixture  of  an  organic  peroxide  with  a  ferment, 
'peroxidase,  which  has  the  property  of  splitting  ojS  atomic,  i.e.  active, 
oxygen  from  the  peroxide.  These  peroxidases  have  the  same  effect 
on  hydrogen  peroxide.  They  must  be  distinguished  from  the  ferment 
catahse,  which  is  present  in  almost  all  animal  and  vegetable  tissues, 
and  which  effects  a  rapid  decomposition  of  hydrogen  peroxide  with  the 
formation  of  molecular  oxygen  : 

2H2O2  =  2H2O  4-  0.2. 

In  the  case  of  a  peroxidase  the  equation  would  be  represented  : 

H0O2  =  H,0  +  0'. 

Many  reactions  are  known  in  chemistry  in  which  the  part  of  a 
peroxidase  is  played  by  an  inorganic  catalyst.  Thus  hydrogen 
peroxide  effects  a  slow  oxidation  of  many  organic  substances,  but  the 
oxidation  is  enormously  hastened  if  to  the  mixture  be  added  a  trace  of 
a  ferrous  salt  (Fenton's  reaction).  The  same  part  may  be  played  by 
salts  of  manganese,  and  it  is  interesting  to  note  that  manganese  forms 
an  essential  constituent  of  the  peroxidase  lactase,  which  is  present  in 
many  plants  and  is  responsible  for  the  formation  of  the  Japanese 
lacquer.  It  effects  a  specific  oxidation  of  hydroquinone  and  pyrogallol. 
The  oxidations  carried  out  by  the  use  of  hydrogen  peroxide,  with  or 
without  a  catalyst  or  peroxidase,  present  a  close  resemblance  to  the 
oxidations  occurring  in  the  animal  body.  Thus  Dakin  has  shown 
that  saturated  fatty  acids,  even  the  higher  members  of  the  series,  arc 
gradually  oxidised  if  warmed  gently  with  hydrogen  peroxide  in  the 
presence  of  ammonia,  and  the  course  of  the  reaction  resembles  in 
many  respects  that  which,  on  other  grounds,  we  have  assumed  to  take 
place  in  the  normal  metabolism  of  the  body. 

We  have  no  evidence  that  hydrogen  peroxide  is  formed  at  any 


1238  PHYSIOLOGY 

time  in  the  body,  though  there  is  some  reason  to  assume  its  formation 
in  the  process  of  carbon  assimilation  in  the  green  leaf.  If  we  adopt 
the  views  of  Bach  and  Chodat  we  must  assume  that  every  animal  cell 
contains  organic  peroxides  as  well  as  peroxidases,  or  else  that  it  can 
under  physiological  conditions  form  these  substances.  Since  there  is 
also  evidence  of  the  presence  of  reducing  substances  in  the  cells,  we 
may  conveniently  assume,  vnih  Ehrlich,  that  distinct  side-chains  of  the 
protoplasmic  molecule  have  specific  afiinities  for  oxygen.  When  all 
these  affinities  are  saturated,  these  side-chains  will  act  as  peroxides, 
parting  with  their  oxygen  with  extreme  ease,  whereas  when  the  greater 
number  are  unsaturated,  the  resultant  effect  will  be  that  of  a  reducing 
agent.  The  same  protoplasmic  molecule  may  therefore,  according 
to  its  state  of  saturation  with  oxygen,  act  either  as  an  oxidising  or 
reducing  agent,  and  can  effect,  probably  through  the  intermediation  of 
specifically  adapted  oxidases,  the  oxidation  of  the  various  food-stuffa 
stored  up  as  the  paraplasm  of  the  cell.  Since  the  oxidative  processes 
are  determined,  not  by  the  presence  of  oxygen,  but  by  the  functional 
activities  of  the  tissue,  we  must  assume  that  the  peroxidases  are  not 
preformed  in  the  cell,  but  exist  as  precursors,  zymogens,  from  which 
they  can  be  set  free  in  accordance  with  the  necessities  of  the 
ceU. 

It  is  probable  that  many  of  the  food-stuffs  or  other  proximate 
constituents  are  not  directly  accessible  to  oxidation,  and  that  the 
first  step  in  their  utilisation  is  a  process  of  cleavage  or  hydrolysis,  which 
itself  involves  the  presence  of  specific  ferments.  Thus,  so  far  as  we 
can  tell,  the  amino-acids  undergo  deamination  before  oxidation.  They 
can  thus  be  stored  up  in  the  cell  either  free  or  in  the  form  of  protein , 
and  present  no  point  of  attack  to  oxygen  until  the  process  of  hydrolysis 
and  deamination  has  taken  place.  This  course  of  events  is  certainly 
true  for  some  of  the  members  of  the  purine  group.  Under  the  action  of 
animal  tissues,  guanine,  as  has  been  shown  by  Schittenhelm  and 
Jones,  is  converted  to  uric  acid.  This  conversion  involves  (1)  the 
deamination  of  guanine  and  its  oxidation  to  xanthine,  and  (2)  the 
oxidation  of  xanthine  to  uric  acid.  In  the  same  way  adenine  is 
converted  into  hypoxanthine,  and  this,  by  a  series  of  oxidations, 
through  xanthine  into  uric  acid.  The  changes  involved  in  the  con- 
version of  guanine  are  shown  as  follows  : 

HN— CO  HN— CO 

NHa.C     C— NH  +  H.H0  =  NH3+    CO  C— NH 

CH 


!i  ?''' 


^ 


N— C— N  HN— C— N 


MECHANISMS  OF  OXIDATION  IN  TISSI^ES 
HN— CO  HN— CO 


1^39 


CO  C— NH  +  0  =    CO  C— NH 


^ 


CH 


CO 


HN— C— N 


HN— C— NH 


Thus  a  whole  series  of  different  ferments  effecting  dissimilar  changes 
may  be  required  to  convert  even  such  a  relatively  simple  body  as  a 
purine  base  into  the  end-products  of  its  metabolism  in  the  body. 


CHAPTER  XVII 
RENAL  EXCRETION 

SECTION  I 

THE  COMPOSITION  AND  CHARACTERS  OF 
THE  URINE 

The  main  product  of  the  oxidation  of  carbon,  namely,  carbon  dioxide, 
is  discharged  by  the  lungs  and  to  a  slight  extent  by  the  skin.  Water, 
taken  as  such  with  the  food,  but  also  derived  to  a  slight  extent  from 
the  oxidation  of  hydrogen,  is  got  rid  of  by  the  lungs,  skin,  and  kidneys^ 
The  salts  of  heavy  metals  when  administered  are  excreted  for  the 
most  part  by  the  alimentary  canal,  e.g.  iron,  bismuth,  mercury.  A 
certain  proportion  of  the  pigmentary  waste  products  of  the  body, 
derived  from  the  breakdown  of  the  blood-pigment,  is  also  got  rid  of 
with  the  faeces.  With  these  exceptions  practically  all  the  waste 
products  resulting  from  metabolism  are  excreted  in  the  urine  by  the 
kidneys.  We  have  thus  to  seek  in  the  composition  of  this  fluid  the 
last  chapter  in  the  metabolic  history  of  a  large  number  of  the  con- 
stituents of  the  body.  Since,  moreover,  the  kidneys  may  excrete  almost 
any  substance  which  circulates  through  their  blood-vessels,  many 
of  the  intermediate  metabolites  may  be  found  in  minute  quantities 
in  the  urine  and  may  be  isolated  by  working  up  large  quantities  of 
this  fluid.  Under  pathological  conditions  these  metabolites  may  appear 
in  the  urine  in  larger  amounts  and  serve  then  as  an  index  to  a  faulty 
metabolism  in  which  there  is  some  interference  with  the  later  stages 
in  the  metabolism  of  fats,  carbohydrates,  or  proteins. 

The  composition  of  the  urine  must  therefore  be  a  variable  one, 
according  to  the  activity  of  the  body,  the  quantity  and  nature  of 
the  food  taken,  and  the  relative  amount  of  water  escaping  by  the 
kidneys,  lungs,  and  skin  respectively.  But  just  as  we  can  describe  a 
normal  diet  for  an  adult  man  of  average  weight,  so  we  can  describe 
an  average  composition  for  the  urine.  The  history  of  the  urinary 
constituents  has  been  given  for  the  most  part  in  the  chapter  dealing 
with  the  metabolism  of  the  proximate  constituents  of  the  food.  It 
will  be  useful,  however,  to  enumerate  in  this  chapter  the  various 

1240 


COMPOSITION  AND  CHARACTERS  OF  URINE       1241 

constituents  of  the  urine  and  to  summarise  their  properties,  prepara- 
tion, and  normal  significance. 

The  urine  of  man  is  a  clear  yellow  fluid  which  froths  when  shaken. 
On  standing,  a  cloud  of  mucus  is  deposited,  consisting  of  a  very  small 
amount  of  nucleoprotein  derived  from  the  epithelial  lining  of  the 
bladder  and  urinary  passages.  In  concentrated  urine  a  deposit  occurs 
on  cooling.  This  deposit  dissolves  when  the  urine  is  warmed,  and 
consists  of  urates.  Under  certain  circumstances  urine  is  turbid  as  it 
is  passed,  but  in  this  case  the  turbidity  generally  consists  of  earthy 
phosphates  and  is  not  cleared  up  by  heating. 

The  colour  of  the  urine  varies  with  its  concentration.  After  severe 
sweating  the  amount  of  water  excreted  by  the  kidneys  is  small,  and 
the  urine  is  therefore  concentrated  and  of  high  colour.  After  copious 
draughts  of  liquid  the  urine  may  be  very  pale  and  dilute. 

Ordinary  urine  has  an  aromatic  odour,  but  this  varies  largely  witli 
the  character  of  the  food.  Many  food  substances  give  characteristic 
odours,  which  may  depend  on  alterations  undergone  by  them  in  their 
passage  through  the  body. 

The  specific  gravity  of  the  urine  is  proportional  to  its  concentra- 
tion. Normally  it  is  1016  to  1020,  though  it  may  rise  as  high  as  1040 
or  sink  as  low  as  1002. 

The  molecular  concentration  of  the  urine  is  almost  always  greater 
than  that  of  the  blood.  Its  osmotic  pressure  may  be  measured  by 
determining  the  depression  of  freezing-point.  The  A  of  urine  normally 
varies  between  0-87  and  2-71  (A  of  blood  =  0*56).  After  copious 
draughts  of  water  the  depression  of  freezing-point  in  the  urine  may  be 
less  than  that  of  serum,  and  may  be  as  small  as  0"25. 

The  reaction  of  urine  is  generally  described  as  acid.  It  is  acid 
to  litmus  and  to  phenolphthalein.  This  is  due  to  the  fact  that  neutral 
constituents  of  the  food  give  rise  to  acid  end-products  in  metabolism. 
The  sulphur  of  proteins  is  converted  into  sulphuric  acid  and  the 
phosphorus  of  lecithin  into  phosphoric  acid.  There  is  thus  a  pre- 
dominance of  acid  radicals  over  bases  in  ordinary  urine.  This  state- 
ment, however,  only  applies  to  man  and  to  carnivora.  In  the  food 
of  herbivora  there  is  a  predominance  of  alkaline  bases.  Vegetable 
acids,  e.g.  tartaric,  malic,  and  citric  acids,  undergo  oxidation  to 
carbonic  acid  in  the  body,  so  that  their  bases  leave  the  body  as  alka- 
line carbonates.  The  urine  of  such  animals  therefore  contains  an 
excess  of  alkaline  carbonates,  and  is  alkaline  in  reaction  and  froths 
on  the  addition  of  an  acid.  If  a  herbivorous  animal  be  starved,  so 
that  it  has  to  live  on  its  own  tissues,  it  becomes  for  the  time,  so  to 
speak,  carnivorous,  and  its  urine  becomes  clear  and  acid.  The  urine 
of  man  can  be  made  alkaline  by  the  ingestion  of  large  quantities  of 
vegetables  or  fruits.     Under  such  circumstances  the  urine  as  passed 


1242 


PHYSIOLOGY 


is  generally  turbid  from  the  presence  of  precipitated  earthy  phos- 
phates. In  determining  the  reaction  of  urine  it  is  usual  to  adhere 
to  one  indicator,  e.g.  phenolphthalein,  and  to  give  the  acidity  in 
terms  of  decinormal  acid,  naming  the  indicator  used.  The  acidity 
[i.e.  the  concentration  of  H  ions)  can  also  be  determined  by  the 
electrical  method.  In  this  way  Hoeber  found  the  acidity  of  human 
urine  to  vary  between  4*7  X  10~'  and  100  X  10~'.  On  the  average  it 
was  49  X  10""'^  in  the  litre. 

THE  AVERAGE  COMPOSITION  OF  THE  URINE.  Several  analyses 
of  the  day's  urine  under  varying  conditions  of  food  have  already  been 
given  [v.  pp.  855,  880).  The  following  may  be  taken  as  a  fair  average 
for  an  adult  man  on  ordinary  mixed  diet  : 

Total  amount  of  urine  =  1500  c.c. 

This  contains  about  60  grm.  of  salts,  of  which  25  grm.  are  inorganic 
and  35  arm.  organic .     These  are  distributed  as  follows  : 


Inorganic  Constituents 

Organic  Constituents 

Sodium  chloride 

15-0  grm. 

Urea 

30-0 

Sulphuric  acid   . 

2-5     „ 

Uric  acid     . 

0-7 

Phosphoric  acid 

2-5     „ 

Creatinine    . 

10 

Potassium 

3-3     „ 

Hippuric  acid 

0-7 

Ammonia 

0-7     „ 

Other  substances 

2-6 

Magnesia  . 

0-5     „ 

Lime 

0-3     „ 

Other  substances 

0-2     „ 

grm. 


The  quantity  of  urine  will  naturally  vary  with  the  water  leaving 
the  body  by  the  kidneys,  and  therefore  according  to  the  habit  of  the 
individual  with  regard  to  the  intake  of  fluids  and  with  his  occupation. 
Thus  after  copious  sweating  the  total  amount  may  fall  to  400  c.c. 
in  the  course  of  the  day.  If  large  draughts  of  liquid  be  taken  it  may 
rise  to  3000  c.c.  or  more.  There  are  also  diurnal  variations  in  the 
amount  secreted,  depending  probably  largely  on  the  circulation 
through  the  kidneys.  The  secretion  is  at  a  minimum  during  sleep, 
and  especially  between  2  and  4  o'clock  in  the  morning.  It  is  at  its 
maximum  during  the  first  hours  after  rising,  and  increases  generally 
after  each  meal.  Muscular  exercise  may  also  give  an  initial  increase 
owing  to  the  greater  vigour  of  the  circulation  associated  with  exercise. 
If  the  exercise  is  severe  enough  to  cause  sweating  or  is  carried  to 
fatigue,  there  may  be  a  consequent  diminution  in  the  amount  of  urine 
secreted. 

THE  INORGANIC  CONSTITUENTS  OF  THE  URINE 
(a)  ACID   RADICALS.     The   chlorides   of    the   urine   are   derived 
almost  entirely  from  the  chlorides  of  the  food.     Though  essential  con- 


COMPOSITION  AND  CHARACTERS  OF  URINE        1243 

stituents  of  the  body  fluids,  it  does  not  seem  that  the  chlorides  enter 
into  organic  combination  with  the  constituents  of  the  cells.  The 
output  of  chlorides,  which  normally  varies  from  6  to  10  grm.  in  the 
course  of  the  day,  will  therefore  depend  on  the  amount  of  chlorides 
taken  in  'with  the  food.  If  these  be  withdrawn  altogether,  the  chlorides 
may  almost  disappear  from  the  urine,  although  the  circulating 
blood  contains  practically  the  same  amount  of  chlorides  as  in  the 
normal  individual,  showing  that  the  body  retains  the  chlorides  neces- 
sary for  the  proper  carrying  out  of  the  vital  processes  as  long  as  possible. 
Chlorides  may  also  disappear  from  the  urine  temporarily  under  various 
pathological  conditions.  This  is  especially  marked  in  cases  of  acute 
pneumonia. 

Sulphates.  The  salts  of  sulphuric  acid  do  not  form  an  important 
constituent  of  the  food.  The  sulphates  of  the  urine  are  derived  almost 
entirely  from  the  oxidation  of  the  sulphur  of  the  protein  molecule. 
The  output  of  sulphates  is  therefore,  like  that  of  urea,  an  index  of 
protein  metabolism.  As  the  nitrogen  of  the  urine  goes  up,  so 
the  sulphates  Avill  increase.  On  an  average  diet  the  ratio  of  urinary 
nitrogen  to  SO  3  is  about  5:1;  though,  owing  to  the  varying  content 
of  different  proteins  in  the  sulphur,  this  ratio  will  naturally  alter  with 
the  nature  of  the  protein  taken  as  food.  The  daily  output  of  sulphuric 
acid  varies  between  1-5  and  3  grm.  SO3.  The  greater  part  of  the 
sulphate  is  present  as  sulphates  of  the  alkahne  metals.  A  certain 
proportion,  about  10  per  cent.,  is  present  in  the  form  of  conjugated 
or  ethereal  sulphates,  chiefly  indoxyl  sulphate.  A  small  proportion 
of  the  sulphur  excreted  in  the  urine  is  present  in  unoxidised  form  as 
so-called  neutral  sulphur.  The  neutral  sulphur  probably  includes 
a  number  of  different  bodies,  among  which  sulphocyanates  and  cystine 
are  the  best  known. 

Inorganic  sulphates  can  bo  precipitated  from  the  urine  by  the  addition 
of  hydrochloric  acid  and  barium  chloride.  On  filtering  off  this  precipitate,  the 
filtrate  contains  the  ethereal  sulphates.  On  boiling,  the  hydrochloric  acid  decom- 
poses these  substances,  setting  free  sulphuric  acid,  which  combines  with  the 
excess  of  barium  present  and  is  precipitated  as  barium  sulphate.  This  second 
precipitate  therefore,  when  weighed,  gives  the  amount  of  ethereal  sulphates 
present.  To  determine  the  neutral  sulphur  the  fluid,  after  the  separation  of 
both  kinds  of  sulpliates,  is  treated  with  sodium  carbonate  to  precipitate  the 
barium,  filtered,  and  the  filtrate  evaporated  to  drjTiess.  The  residue  is  then 
ignited  with  potassium  nitrate,  cooled,  and  extracted  with  water.  By  this  treat- 
ment all  the  neutral  sulphur  is  converted  into  sulphates,  which  can  bo  tlirown 
down  from  the  solution  with  barium  chloride  and  weighed  in  the  usual  way. 

Phosphates.  The  phosphates  of  the  urine  are  derived  partly  from 
the  phosphates  of  the  food,  partly  from  the  oxidation  of  the  organic 
phosphorus-containing  constituents  of  the  food  and  of  the  tissues, 
e.g.    nuclein,    lecithin,    &c.      If    the    food    contains    much    calcium 


12U  PHYSIOLOGY 

and  magnesium,  the  amount  of  phosphates  excreted  by  the  urine 
diminishes,  since  these  substances  are  excreted  with  the  faeces  as 
calcium  and  magnesium  phosphates.  According  to  the  diet  therefore, 
phosphoric  acid  may  be  excreted  either  by  the  intestine  or  by  the 
kidneys.  The  amount  of  phosphates,  reckoned  as  P2O5,  excreted 
in  the  course  of  the  day  may  vary  between  1  and  5  grm.  In  the  urine 
the  phosphates  exist  as  a  mixture  of  the  mono-  and  di-sodium 
phosphates,  the  relative  amounts  of  the  two  varying  with  the 
acidity  of  the  urine.  If  the  urine  is  neutral  or  alkaline  there  is 
very  often  a  deposit  of  earthy  phosphates.  Whether  this  deposit 
is  present  or  not  depends  on  the  varying  solubiUty  of  the  different 
calcium  and  magnesium  phosphates.  Thus  the  mono-magnesium 
phosphate  MgH4(P04)2  and  the  mono-calcium  phosphate  CaH4(P04)2 
are  both  fairly  soluble  in  water,  and  their  solubility  is  increased  by 
the  presence  of  neutral  salts.  With  increased  acidity  of  the  urine  the 
proportion  of  the  two  bases  present  in  these  forms  is  diminished.  The 
di-magnesium  and  di-calcium  phosphates  are  only  slightly  soluble  in 
water,  and  the  latter  would,  if  present  in  the  urine,  be  deposited. 
One  may  indeed,  in  slightly  acid  urine,  find  the  di-calciimi  phosphate 
occasionally  present  as  a  crystalline  deposit.  On  heating  the  urine 
the  di-calcium  phosphate  breaks  up  into  a  mono-calcium  phosphate 
and  a  tri-calcium  phosphate,  while  the  acidity  of  the  urine  is  increased 
by  the  solution  of  the  mono-calcium  phosphate.  Alkaline  urine  will 
always  present  a  precipitate  of  tri-calcium  phosphate  Ca3(P204)8. 
When  normal  urine  is  allowed  to  stand,  the  urea  is  converted  by  the 
presence  of  micro-organisms  into  ammonium  carbonate,  and  the  urine 
becomes  alkaline.  Under  such  conditions  we  may  often  find  a  crystal- 
line precipitate  of  ammonium  magnesiimi  phosphate,  NH4MgP04,  the 
so-called  '  triple  phosphate.' 

(6)  THE  BASES  OF  THE  URINE.  The  bases  include  potassium, 
sodium,  ammonium,  magnesium,  and  calcium. 

The  amount  of  potash  excreted  in  twenty-four  hours  varies  between 
19  and  3"2  grm.,  according  to  the  nature  of  the  food  taken.  With  a 
large  meat  diet,  which  contains  considerable  quantities  of  potassium, 
the  output  of  this  base  is  increased.  In  fasting  there  is  also  an  increase 
in  the  output  of  potash,  owing  to  the  utilisation  of  the  tissues  of  the 
body  which  themselves  are  rich  in  potassium. 

The  amount  of  sodium  excreted  in  the  twenty-four  hours  varies 
on  the  average  between  4  and  5  grm.,  but  depends  very  largely  on  the 
quantity  of  sodium  chloride  taken  with  the  diet.  The  alkaline  earths, 
lime  and  magnesia,  are  invariably  present  in  urine,  but  in  much 
smaller  quantities  than  the  alkaline  metals.  The  average  amount  of 
these  two  bases  in  the  twenty-four  hours  varies  in  each  case  between 
0- 1  and  02  grm.     Their  output  by  the  urine  is  no  criterion  of  the  amount 


COMPOSITION  AND  CHARACTERS  OF  URINE         1245 

taken  in  with  the  food  or  absorbed  from  the  intestines,  since  both  these 
bases  may  be  re-excreted  intf)  the  gut  and  appear  as  insoluble  phos- 
phates in  the  fa3ces. 

Normal  human  urine  always  contains  a  small  amount  of  ammonia, 
on  an  average  between  0'6  and  08  grm.  in  the  twenty-four  hours. 
As  we  have  already  seen,  in  dealing  with  the  origin  of  urea  in  the 
body,  the  quantity  of  ammonia  in  the  urine  is  an  index  to  the  excess 
of  acids  over  bases  which  have  to  be  excreted  by  this  fluid.  Thus  it 
is  easily  possible  to  increase  the  proportional  amount  of  ammonia  in 
the  urine  by  the  administration  of  mineral  acids.  An  increase  of 
the  proportion  of  nitrogen  excreted  as  ammonia,  apart  from  the 
administration  of  acids  with  the  food,  is  an  important  indication  of 
the  formation  of  abnormal  acid  substances  in  metabolism.  Thus  in 
diabetes,  when  the  last  stages  of  fat  oxidation  are  in  default,  so  that 
the  oxy-fatty  acids,  |3-oxybutyric  and  aceto-acetic  acids,  accumulate 
in  the  body,  there  is  always  a  considerable  rise  in  the  ammonia  of  the 
urine. 

It  is  usual  to  reckon  iron  among  the  bases  which  may  be  excreted 
by  the  urine.  The  amount  of  this  substance  in  the  urine  is 
extremely  small,  as  a  rule  less  than  5  mg.  in  the  day.  It  affords  no 
clue  to  the  iron  metabolism  of  the  body,  since  the  main  channel  of 
excretion  of  this  substance  is  the  intestine. 

ORGANIC  CONSTITUENTS  OF  THE   URINE 

Almost  all  these  constituents  contain  nitrogen,  which  in  man  is 
distributed  among  the  various  urinary  constituents  as  follows : 

Urea  .....     85-90  per  cent. 

Ammonia  .....       2^         ,, 

Creatinine  .  .  .  .  .3 

Uric  acid  .....       1-3 

About  G  per  cent,  of  the  urinary  nitrogen  is  in  the  form  of  other  sub- 
stances, such  as  hippuric  acid,  pigments,  &c. 

.        /NH, 
UREA  or  CARBAMIDE,    Q0(  can  be  regarded  as  derived 

^NHa 
OH 
from  carbonic  acid,  CO  by  the  replacement  of  each  OH  group  by 

"^OH 
an  NH-;  group.     It  is  isomeric  with  amnioniuiu  t-yaiuite,  NH.,CNO. 
If  a  solution  of  potassium  cyanate  and  amnioniuiu  chloride  be  warmed 
together   and  evaporated,  crystals  of  urea  may  be  obtained  in  long 
colourless  prisms  (Fig.  .514)  without  any  water  of  crystallisation.    It 


1246 


PHYSIOLOGY 


is  soluble  in  water  and  alcohol,  and  insoluble  in  ether.  Its  solutions 
_^,^__^____^___^__^__,_,^_^^  are  neutral  in  reaction,  but  it 
^  -^^^^^^^^^B  forms  crystalline  salts  with  strong 
■^r  ;  ^^^H     acids.      Thus  urea  nitrate,  which 

^W'^-:\    '  ^H     is    produced  by   treating    strong 

W     '    '  ^k     solutions    of    urea    with    concen- 

f  1     trated   nitric  acid,   forms   micro- 

I  I     scopic  rhombic   plates  which  are 

extremely  insoluble,  so  that  their 
formation  may  be  used  as  a  test 
for  urea  (Fig.  515).  With  oxalic 
acid  urea  solutions  yield  an  in- 
soluble oxalate,  also  in  typical 
crystals.  Urea  when  heated  melts 
at  about  130°  C.  On  further 
heating,  it  undergoes  decompo- 
sition, giving  off  ammonia  and  forming  biuret,  as  follows  : 


Fig.    514.     Urea.     (Funke.) 


NH, 


NH, 


C0( 


2    CO.  -        )NH   +NH3. 

\      \nhJ     C0( 

NH2 

At  the  same  time  a  certain  amount  of  cyanic  acid  is  formed,  and 
this  polymerises  to  cyanuric  acid,  H3C3N3O3.  On  heating  with 
alkalies  or  with  strong  acids  urea  undergoes  hydrolysis,  with  the  pro- 
duction of  carbon  dioxide  and  ammonia  : 

CON2H4  +  H2O  -  CO2  +  (NH3)2. 

The  same  change  is  effected  in  urea  by  certain  micro-organisms,  e.g. 
the  micrococcus  ureas,  which  is  responsible  for  the  ammoniacal  change 
which  occurs  in  urine  when  exposed 
to  the  air. 

Urea,  being  the  chief  nitrogenous 
constituent  of  the  urine,  is  the 
most  important  index  to  the  protein 
metabolism  of  the  body.  As  we 
have  seen,  urea  may  be  regarded 
as  partly  exogenous,  partly  endo- 
genous. The  greater  part  of  the 
30  grm.  excreted  by  a  normal  indi- 
vidual in  the  course  of  the  day  is  derived  directly  from  the  proteins  of 
the  foods,  as  a  result  of  the  deamination  of  the  amino-acids,  which 
occurs  shortly  after  their  absorptioji.     The  ammonia  thus  formed  is 


Urea  nitrate. 


Urea  oxalate. 


COMPOSITION  AND  CHARACTERS  OF  URINE        1247 

carried  to  the  liver,  where  it  undergoes  dehydration  with  the  produc- 
tion of  urea.  Its  amount  will  therefore  be  directly  proportional  to 
the  amount  of  protein  taken  as  food.  A  smaller  proportion  is  derived 
from  the  breakdown  of  the  tissues  of  the  body.  This  endogenous 
moiety  may  undergo  considerable  increase  under  any  conditions  which 
cause  a  rapid  disintegration  of  the  tissues.  Thus  there  is  a  large  rise 
in  the  urea  output,  even  in  a  starving  individual,  in  febrile  conditions. 

In  order  to  prepare  urea  from  urine  advantage  may  be  taken  of  the  insolu- 
bility of  its  combination  ^v■itl^  nitric  acid.  Urine  is  concentrated  to  about  one- 
sixth  of  its  bulk.  It  is  then  cooled  and  treated  Avith  twice  its  volume  of  pure 
concentrated  nitric  acid,  care  being  taken  to  keep  the  whole  mixture  cool.  Urea 
nitrate  is  precipitated.  The  precipitate  is  collected,  dried  roughly  b^'  pressing 
between  filter  paper,  and  then  rubbed  up  with  fresh  barium  carbonate.  Barium 
nitrate  is  formed  and  urea  set  free.  The  whole  mass  is  dried  and  treated  with 
hot  absolute  alcohol,  in  wliich  the  barium  nitrate  is  insoluble.  On  filtering  off 
the  barium  nitrate  a  pure  solution  of  urea  is  obtained  from  wliich  the  urea  Avill 
crystallise  on  allowing  the  alcohol  to  evaporate. 

CREATININE.  Creatinine  is  a  normal  constituent  of  urine,  in 
which  it  occurs  in  quantities  of  0"8  to  r3  grm.  in  the  twenty-four  hours. 
It  is  easily  produced  from  creatine  by  boiling  the  latter  with  strong 
hydrochloric  acid,  when  a  process  of  dehydration  occurs.  Creatine 
has  the  formula  : 

NH2 

I  \   - 

NH  =.  C— N(CH3)CH2.COOH. 
On  dehydration  it  is  converted  into  creatinine  :  t- 

NH 


NH  =  C— N(CH3)CH2C0 

Creatinine  maj;^  be  obtained  from  urine  in  the  following  way.  The  urine  is 
made  alkaline  with  milk  of  lime  and  treated  with  calcium  chloride  and  filtered. 
The  filtrate  is  slightly  acidified  with  acetic  acid  and  evaporated  on  the  water 
bath  to  a  syrupy  consistence.  A  little  sodium  acetate  is  added  and  the  mixture 
extracted  with  alcohol.  The  filtered  alcohohc  extract  is  now  treated  with  a 
concentrated  neutral  alcoholic  solution  of  zinc  chloride.  A  crystaUine  precipitate 
of  creatinine  zinc  chloride  is  produced.  After  two  days  this  precipitate  is  collected 
on  a  filter,  washed  with  alcohol,  dissolved  in  water,  and  then  boiled  for  a  quarter 
of  an  hour  with  lead  hydrate.  The  mixture  is  then  filtered  and  the  filtrate  evapo- 
rated to  dryness.  I'lie  dry  residue  is  now  extracted  with  cold  alcolK)l  and  filtered. 
On  allowing  the  alcohol  to  evaporate,  crystals  of  creatinine  separate  out  (Fig. 
510).    It  gives  the  foUoAving  tests  : 

(1)  WEYL'S  TEST.  On  treating  a  solution  of  creatinine  witli  a  small  quan- 
tity of  very  (iilute  sodium  nitroprusside  solution  and  then  with  weak  cau.stic 
alkali,  a  rich  ruby-red  colour  is  produced  wiiich  gradually  changes  to  yellow. 
On  now  adding  acetic  acid  and  warming,  the  solution  becomes  green  and  then 
blue,  and  finally  a  precipitate  of  Prussian  blue  is  formed. 

(2)  JAFFE'S  TEST,  On  treating  a  solution  of  creatinine  with  a  few  drops 
of  a  watery  solution  of  picric  acid  and  dilute  caustic  polasli.  an  intense  red 


1248 


PHYSIOLOGY 


colour  is  produced.    This  reaction  is  made  use  of  for  the  quantitative  estimation 
of  creatinine  in  the  urine. 

Like  the  other  nitrogenous  constituents,  creatinine  can  be  regarded 
as  partly  exogenous,  partly  endogenous  in  origin.  The  exogenous 
part  is  derived  from  the  creatine  contained  in  meat.  When  meat  is 
excluded  from  the  diet  the  output  of  creatinine  becomes  remarkably 
constant  and  is  little  affected  by  the  total  amount  of  proteins  taken, 
the  amount  excreted  during  starvation  being  practically  identical  with 


¥iG.  GIG.     Creatinine.     (Funke.) 


Fig.  o17.     Uric  acid.     (Funke.) 


that  excreted  on  a  full  protein-free  diet.     It  is  said  to  be  increased 
during  febrile  conditions  and  as  a  result  of  violent  muscular  exorcise. 
URIC  ACID.     Uric  acid  is  2-6-8-trioxypurin. 


HN— CO 


OC    C— NH. 


HN    0— NH^ 


)C0 


N=C(0H) 

or  (HO)C     C— NH 

II      II 

N— C  — N 


^C(OH) 


Uric  acid  forms  small  rhombic  crystals.  The  crystalline  form  varies 
considerably  in  the  presence  of  impurities.  The  different  forms  of  uric 
acid  crystal  which  may  occur  in  the  urine  are  shown  in  the  accompany- 
ing figure  (Fig.  517).  It  is  extremely  insoluble  in  pure  water,  one  part 
of  uric  acid  requiring  39,000  parts  of  water  at  18°  C.  for  its  solution. 
It  is  easily  soluble  in  concentrated  sulphuric  acid  and  alkalies. 

It  may  be  prepared  from  liuman  urine  or  from  guano,  whicli  consists  almost 
entirely  of  urates.  In  order  to  prepare  it  from  guano,  this  is  dissolved  with 
the  aid  of  heat  in  dilute  sodium  carbonate,  filtered,  and  the  filtrate  treated  with 
a  few  drops  of  concentrated  hydrocliloric  acid  and  boiled.  On  allowing  to  cool, 
the  uric  acid  crystallises  out.  From  urine  uric  acid  may  be  obtained  by  adding 
one-fiftieth  of  its  volume  of  concentrated  hydrochloric  acid  and  allowing  to 


COMPOSITION  AND  CHARACTERS  OF  URINE       1249 

stand  for  two  days.  The  uric  acid  is  tlirown  douii  in  small  dark-red  or  brown 
crystals.  They  can  be  collected  on  a  filter,  dissolved  in  alkali,  decdiorised  by 
boiling  with  animal  charcoal,  and  the  pure  acid  thrown  down  as  before  hydro- 
chloric acid. 

A  more  convenient  method  of  preparation  from  human  urine  is  based  on 
the  fact  that  ammonium  urate  is  insoluble  in  concentrated  solutions  of  ammo- 
nium chloride  (Hoijkins).  The  urine  is  saturated  with  crystals  of  ammonium 
chloride  and  a  few  drops  of  strong  ammonia  added.  A  gelatinous  precipitate  of 
ammonium  urate  is  produced.  This  is  collected  on  a  filter,  washed  off  with  a 
minimum  amount  of  hot  water  into  a  beaker,  and  a  few  drops  of  hydrochloric 
acid  added.  The  mixture  is  boiled  and  then  allowed  to  cool,  when  the  pure  acid 
crystalhses  out. 

TESTS  FOR  URIC   ACID 

(1)  MUREXIDE  TEST.  If  a  small  quantity  of  uric  acid  be  treated  with 
a  little  strong  nitric  acid  and  the  whole  evaporated  to  dryness  on  the  water- 
bath,  an  orange-red  residue  is  obtained,  which  on  treatment  with  ammonia 
yields  a  fine  purple  colour.  If  a  drop  of  sodium  hj'drate  be  now  added  the  purple 
changes  to  blue.    Instead  of  nitric  acid,  bromine  water  may  be  employed. 

(2)  SCHIFF'S  TEST.  If  uric  acid  be  dissolved  in  a  httle  soda  and  a  drop  be 
placed  on  filter  paper  previously  moistened  ^nth  silver  nitrate,  a  yellow  or  bro^ra 
spot  is  produced. 

(3)  On  boiling  uric  acid  with  Fehhng's  solution  for  some  time,  a  yellowish 
precipitate  of  cuprous  hydrate  is  produced. 

(4)  An  alkaUne  solution  of  uric  acid  on  treatment  with  a  few  drops  of  a 
solution  of  phosphomolybdic  acid  gives  a  dark  blue  precipitate  with  a  metallic 
lustre,  consisting  of  microscopic  prismatic  crystals. 

(5)  With  sodium  hypobromite  uric  acid  is  decomposed,  giving  off  about  half 
of  its  nitrogen  as  the  free  gas. 

URATES.  Of  the  four  hydrogen  atoms  in  uric  acid  two  can  be 
replaced  by  metallic  radicals.  Uric  acid  thus  acts  as  a  weak  dibasic 
acid.  It  forms  three  orders  of  salts,  namely,  the  neutral  urates,  the 
bi-urates,  and  the  quadri-uiates.  The  neutral  urates,  M'gU,  are  very 
unstable,  and  only  exist  in  the  presence  of  caustic  alkalies.  They  are 
decomposed  even  by  the  carbonic  acid  of  the  atmosphere.  The  bi- 
urates,  MHU,  are  the  most  stable  of  the  urates.  They  may  be  pre- 
pared by  dissolving  uric  acid  with  the  aid  of  heat  in  weak  solutions 
of  the  alkaline  carbonates,  from  which  they  separate,  on  cooling,  in 
stellar  crystals. 

The  quadri-urates  have  the  formula  H2U,  MHU.  They  may 
be  prepared  by  boiling  uric  acid  w^ith  dilute  solutions  of  potassium 
acetate.  On  cooling  the  mixture  the  quadri-urates  separate  as  an 
amorphous  precipitate  or  in  crystalline  spheres.  The  quadri-urates 
are  extremely  unstable,  and  in  the  presence  of  water  are  broken  up 
into  the  bi-urates  and  free  uric  acid.  It  is  probable  that  under 
normal  conditions  the  greater  part  of  the  uric  acid  in  the  urine  is 
present  in  the  form  of  a  quadri-urate  (Roberts),  and  the  so-called  lateri- 
tious  deposit,  the  brick-red  amorphous  precipitate  of  urates  which 
occurs  in  concentrated  urine  on  coohng,  consists  of  these  quadri-urates. 

79 


1250  PHYSIOLOGY 

The  exact  condition  of  the  urate,  however,  will  depend  on  the  reaction 
of  the  urine.  A  bi-urate,  with  acid  sodium  phosphate,  is  decomposed 
with  the  formation  of  uric  acid  in  the  following  way  : 

MHU  +  MH2PO4  =  H2U  +  M2HPO4. 

Thus  the  quadri-urates  present  in  the  urine  immediately  after  its 
secretion  will  tend  to  undergo  spontaneous  decomposition  into  uric 
acid  and  the  bi-urate,  and  the  latter  itself  may  be  decomposed  with 
the  formation  of  uric  acid  and  alkaline  phosphate.  We  see  therefore 
that  when  the  urine  is  acid,  i.e.  there  is  a  predominance  of  acid  phos- 
phates, there  will  be  a  tendency  to  the  precipitation  of  uric  acid  in  the 
urinary  passages.  If,  however,  the  di-sodium  phosphate  be  in  excess 
the  uric  acid  may  be  kept  in  solution  as  the  quadri-urate  or  even 
as  the  bi-urate. 

The  uric  acid  of  the  urine  is  derived  almost  entirely  from  the 
purine  metabolism  of  the  body.  The  uric  acid  may  be  endogenous  or 
exogenous,  i.e.  may  be  derived  from  the  breaking  down  of  the  nucleins 
of  the  cells  or  by  a  direct  transformation  of  the  nucleins  contained  in 
the  food.  The  amount  passed  daily  varies  between  0-4  and  1  grm., 
according  to  the  nature  of  the  diet.  It  is  not  absent  from  the  urine 
even  during  complete  starvation.  It  is  increased  when  foods  are 
ingested  rich  in  nucleins,  such  as  liver  or  sweetbreads,  or  in  any  other 
precursors  of  uric  acid,  e.g.  hypoxanthine,  such  as  meat  or  meat  extract. 
We  have  no  evidence  that  the  urinary  uric  acid  in  the  mammal  is 
formed  by  synthesis,  though  this  is  the  manner  in  which  the  greater 
part  of  the  uric  acid  forming  the  nitrogenous  excreta  of  birds  and 
reptiles  is  formed. 

Small  traces  of  purine  bases  also  occur  in  urine,  namely,  xanthine, 
hypoxanthine,  and  adenine.  When  tea  and  coffee  are  taken  the 
methyl-purines  may  occur,  namely,  caffeine,  theobromine,  and  their 
derivatives. 

HIPPURIC  ACID  is  a  frequent,  though  not  a  constant,  constituent 
of  human  urine.  It  is  derived  from  benzoic  acid  or  from  an  aromatic 
substance  which  on  oxidation  can  give  rise  to  benzoic  acid.  In  the 
kidneys  the  benzoic  acid  is  conjugated  with  glycine  to  form  hippuric 
acid.  Thus  the  amount  of  hippuric  acid  excreted  in  the  day  may  vary 
between  0-1  and  1  grm.  After  a  diet  rich  in  fruit  or  vegetables  its 
amount  may  rise  to  2  grm.  It  is  present  in  considerable  quantities  in 
the  urine  of  herbivora  and  may  be  most  easily  prepared  from  horses' 
urine.     Hippuric  acid  has  the  formula  : 

CeH.CO 

HNCH,COOH 


COMPOSITION  AND  CHARACTERS  OF  URINE 


1251 


It  can  be  obtained  in  milk-white  crystals  (Fig.  518),  which  are  only 
slightly  soluble  in  cold  water,  but  easily  soluble  in  alcohol  ether,  and 
acetic  acid.  It  is  insoluble  in  petroleum,  ether,  and  benzol.  On 
heating,  it  is  broken  up  into  benzoic  acid  and  glycine.  On  heating 
with  concentrated  nitric  acid  it  forms  nitro-benzol,  which  can  be 
recognised  by  its  characteristic  smell  of  bitter  ahnonds. 

In  order  to  extract  it  from  the  urine,  the  urine  is  made  alkaline  wth  sodium 
carbonate,  filtered,  and  the  filtrate  evaporated  to  a  syrupy  consistence.  Tliis 
is  then  treated  with  alcohol,  the  alcohol  evaporated,  and  the  residue  repeatedly 
extracted  with  acetic  ether.  The  acetic  ether  is  collected,  evaporated  to  dryness, 
and  the  residue  repeatedly  extracted  with  petroleum  ether  to  remove  the  benzoic 
acid  and  fat.  What  is  left  beliind  is 
hippuric  acid,  which  can  be  purified  by 
recrystallisation  from  alcohol  or  ether. 

OTHER  AROMATIC  SUB- 
STANCES. The  chief  of  these  is 
the  so-called  '  urinary  indican,'  or 
potassium-indoxyl-sulphate.  Thi« 
is  derived  from  the  indol  produced 
in  the  intestines  from  the  trypto- 
phane contained  in  the  proteins 
of  the  food,  the  change  being 
effected  by  the  influence  of  the 
micro-organisms  of  putrefaction. 
The  amount  of  the  conjugated 
sulphates  in  the  urine  is  thus  an 
index  of  the  extent  of  putrefaction  in  the  intestines.  In  dogs, 
when  the  intestine  has  been  disinfected  by  repeated  doses  of  calomel, 
the  conjugated  sulphates  entirely  disappear  from  the  urine.  Urinary 
indican  has  the  formula  : 

H 

C 

HC       C COSO,OH 


Fig.   518.     Hippuiic  acid.     (Funke.) 


HC       C      CH 


C 
H 


N 
H 


In  addition  to  the  tests  for  conjugated  sulphates  mentioned  earlier,  the 
indoxyl-sulpliate  can  bo  detected  by  various  methods  dependent  on  the  forma- 
tion of  indigo  blue.  The  urine  is  treated  with  an  equal  volume  of  concentrated 
hydrochloric  acid  and  several  cubic  centimetres  of  chloroform  added.  A  con- 
centrated solution  of  chloride  of  lime  is  now  added  drop  by  drop,  shaking  after 
the  addition  of  each  drop.    A  blue  colour  is  produced  wliich  is  extracted  by  the 


1252  PHYSIOLOGY 

chloroform.    It  is  important  not  to  add  too  much  chlopidc  of  hme,  as  otherwise 
the  blue  colour  first  produced  will  be  destroyed  by  further  oxidation. 

THE  URINARY  PIGMENTS.  Normal  mine  gives  no  definite 
absorption  bands.  It  owes  its  colour  to  the  presence  of  a  yellow  pig- 
ment, urochrome.  In  order  to  separate  urochrome  from  urine,  the 
urine  is  saturated  with  crystals  of  ammonimn  sulphate  and  filtered. 
The  filtrate,  which  still  contains  nearly  all  the  colour  of  the  urine,  is 
shaken  up  with  alcohol,  which  withdraws  the  greater  part  of  the 
colouring-matter.  On  concentrating  the  alcoholic  solution  and  pour- 
ing it  into  an  equal  volume  of  ether,  an  amorphous  brown  precipitate 
falls,  which  is  the  urochrome.  Urochrome,  on  treatment  with  alde- 
hyde, yields  a  pigment  closely  similar  to,  if  not  identical  with,  urobilin. 
On  the  other  hand,  urobilin,  treated  with  potassium  permanganate, 
is  converted  into  a  substance  practically  identical  with  urochrome. 
Urochrome  must  therefore  be  derived  from  the  same  source  as  urobilin. 

Urobilin  is  rarely  present  in  normal  urine,  and  then  only  in  the  form 
of  a  chromogen,  from  which  it  must  be  set  free  by  acidification.  In 
certain  pathological  conditions,  especially  in  cirrhosis  of  the  liver, 
urobilin  may  occur  in  the  urine  in  considerable  quantities.  In  order 
to  extract  urobilin  from  such  urine,  the  urates  are  first  precipitated 
by  saturation  with  ammoniiun  chloride,  and  the  filtrate  is  then 
saturated  with  ammonimn  sulphate  and  a  drop  of  sulphuric  added.  On 
shaking  the  fluid  up  with  a  mixture  of  two  parts  ether  and  one  part 
chloroform,  the  urobilin  is  taken  up  by  the  latter.  The  ether-chloro- 
form solution  is  separated  ofi  and  shaken  up  wnth  caustic  soda,  when 
the  urobilin  passes  entirely  into  the  alkaline  solution. 

Urobilin  in  solution  gives  a  single  absorption  band  betw^een  the 
lines  h  and  f,  i.e.  at  the  junction  of  the  green  and  blue  of  the  spectrum. 
On  treating  with  zinc  chloride  and  ammonia  its  solutions  show  a 
w^ell-marked  green  fluorescence.  The  urobilin  of  urine  is  identical  with 
stercobilin,  the  colouring-matter  of  the  fseces.  It  is  formed  from  bile 
when  the  latter  decomposes,  and  is  probably  produced  in  the  intes- 
tines by  the  action  of  micro-organisms  on  bile  pigment. 

Other  pigments  which  may  occur  in  urine  are  uroerythrin  and 
hsematbporphyrin.  Uroerythrin  gives  the  pink  colour  to  urate  sedi- 
ments. Its  chemical  nature  is  not  known.  It  is  distinguished  by  the 
fact  that  on  addition  of  a  caustic  soda  the  pink  colour  is  changed  to 
green.  On  suspending  the  red-coloured  precipitate  of  urates  in  hot 
water  and  extracting  vnih.  amyl  alcohol,  a  pink  solution  is  obtained 
which  shows  two  absorption  bands  in  the  green  part  of  the  spectrum. 

Hcemato'por'phyrin  is  only  present  in  very  small  amounts  in  normal 
urine,  but  under  certain  conditions,  especially  after  poisoning  with 
sulphonal,  it  may  occur  in  such  large  quantities  as  to  give  the 
urine  a  deep  purple  colour.     Under  these  circumstances  it  is  found 


COMPOSITION  AND  CHARACTERS  OF  URINE       1253 

in  the  form  of  alkaline  haematoporphyrin  and  gives  the  characteristic 
absorption  bands  of  the  latter. 

Urorosein  is  a  name  that  has  been  given  to  a  pigment  which  is 
formed  when  the  urine  is  treated  with  strong  mineral  acids.  It  is 
probably  an  indol  derivative.  It  gives  a  single  absorption  band 
between  the  lines  d  and  e. 

ABNORMAL  CONSTITUENTS    OF  THE    URINE 

A  very  large  number  of  substances  occur  in  the  urine  in  minute 
traces  and  may  be  detected  when  large  quantities  of  this  fluid  are 
worked  up  at  one  time.  Most  of  the  so-called  pathological  con- 
stituents may  be  detected  in  this  way  in  normal  urine.  It  is  only 
when  they  occur  in  easily  detectable  amounts  that  their  presence 
becomes  of  any  significance. 

COAGULABLE  PROTEIN.  Under  normal  circumstances  urine  is 
free  from  any  coagulable  protein  except  the  small  traces  of  mucinous 
material,  nucleoprotein,  which  gives  the  cloudiness  to  the  urine.  If 
the  kidney-cells  are  damaged  by  disease,  by  interference  with  their 
blood-supply,  or  by  circulating  poisons,  the  glomerular  epithehum 
permits  the  passage  of  a  certain  amount  of  the  proteins  of  the  plasma. 
Under  these  circumstances,  if  small  pieces  of  the  kidney  be  plunged 
into  boihng  water,  the  coagulated  protein  may  be  seen  in  Bowman's 
capsule.  The  presence  of  coagulable  protein  (generally  spoken  of  as 
albimaen)  in  the  urine  is  significant  of  the  pathological  conditions 
of  the  kidney  associated  with  Bright's  disease.  A  small  trace 
will  generally  be  found  in  the  urine  which  is  passed  shortly  after 
taking  muscular  exercise.  Under  this  condition  the  presence  of 
albumen  in  the  urine  has  no  pathognomic  significance. 

The  proteins  generally  found  are  identical  with  those  of  the  blood- 
plasma  and  consist  of  serum  albumen  and  serum  globulin.  Their 
presence  in  the  urine  may  be  detected  by  the  precipitate  produced  on 
boiling.  In  carrying  out  this  test  a  few  cubic  centimetres  of  saturated 
salt  solution  should  be  added  and  one  or  two  drops  of  dilute  acetic 
acid.  A  more  delicate  test  is  that  known  as  Heller's.  Some  strong 
nitric  acid  is  placed  in  a  test-tube  and  the  urine  is  poured  carefully 
down  the  side  of  the  tube  so  as  to  form  a  layer  on  the  surface  of  the 
nitric  acid.  If  albumen  be  present  a  white  ring  is  formed  at  the 
junction  of  the  two  liquids. 

SUGAR.  Normal  urine  contains  about  one  part  per  thousand  of 
glucose.  In  diabetes  the  power  of  assimilating  carbohydrates  is 
diminished  or  destroyed.  The  amount  of  sugar  in  the  blood  is 
increased,  and  sugar  appears  in  large  quantities  in  the  urine.  The  sugar 
is  practically  always  glucose  or  dextrose.  Lactose  may  occur  in  the 
urine  of  nursing  women  even  in  conditions  of  health.     Since  both 


1254 


PHYSIOLOGY 


these  sugars  will  reduce  Fehling's  solution  it  becomes  important  to 
be  able  to  distinguish  between  them. 

The  following  tests  are  used  for  the  detection  of  abnormal  amounts  of  sugar 
in  the  urine  : 

(1)  FEHLING'S  TEST.      The  urine  is  boiled  with    Fehling's    solution    (an 


Fig.  519.     Glucosazone. 

alkaline  solution  of  copper  sulphate  to  which  Rochelle  salt  has  been  added  to 
keep  the  cupric  hydrate  in  solution).    Under  the  action  of  glucose  or  lactose  the 


Fig.  520.     Lactosazone.     (Plimmer.) 

cupric  hydrate  is  reduced  to  an  insoluble  cuprous  hydrate,  which  forms  a  yellow 
or  rod  precipitate. 

(2)  The  phenylhydrazine  test  may  be  carried  out  as  follows  :   2  c.c.  of  50  per 
cent,  acetic  acid,  saturated  with  sodium  acetate,  and  two  drops  of  phenylhydra- 


COMPOSITION  AND  CHARACTERS  OF  URINE       1255 

zinc  are  added  to  5  c.c.  of  urine.  The  mixture  is  evaporated  down  to  3  c.c, 
rapidly  cooled,  and  again  warmed  in  a  water  bath.  It  is  then  allowed  to  cool 
slowly.  Crystals  of  the  corresponding  osazono  separate  out  in  the  hot  liquid  in 
the  case  of  glucosazone,  on  cooling  in  the  case  of  lactosazone  (Figs.  519,  520). 

(.3)  The  most  convenient  way  of  distinguisliing  between  lactose  and  glucose 
is  by  adding  a  little  yeast  to  the  urine  in  an  inverted  test-tube.  If  glucose  be  the 
sugar  present,  it  is  fermented  by  the  yeast  \vith  the  production  of  carbon  dioxide, 
which  collects  at  the  top  of  the  test-tube. 

In  rare  circumstances  fructose  or  tevulose,  or  pentose  may  be 
found  in  the  urine.  The  former  would  be  detected  by  the  fact  that 
it  rotates  polarised  light  to  the  left,  instead  of  to  the  right,  as  is  the 
case  with  glucose. 

GLYCURONIC  ACID.  Small  traces  of  this  are  present  in  normal 
urine.  It  occurs  as  a  conjugated  acid  after  the  administration  of 
various  substances,  e.g.  camphor  and  chloral.  If  phenol,  indol,  or 
scatol  be  given  to  an  animal  which  is  receiving  very  little  protein  in 
its  diet,  these  substances  will  leave  the  body  conjugPated,  not  with 
sulphuric  acid,  but  with  glycuronic  acid.  Glycuronic  acid  may  be 
regarded  as  the  first  product  of  oxidp-tion  of  glucose,  having  the 
formula : 

COOH 

(CHOH), 

CHO 

It  reduces  Fehling's  solution  and  rotates  the  plane  of  polarised  light 
to  the  left. 

OXY-FATTY  ACIDS  AND  ACETONE.  These  substances  occur 
often  associated  with  glucose  in  diabetes,  especially  towards  the  latter 
stages.  They  represent  the  penultimate  stages  in  the  oxidation  of  the 
fats.     Their  relation  to  one  another  is  seen  from  their  formula) : 

CH3  CH3  CH3 

CHOH  CO  CO 

I  I  I 

CH2  CH2  CH3 

I  I 

CO(JH  COOH 

Oxybutyric  Aceto-acotic  Acetone 

acid  acid 

They  may  also  occur  in  any  condition  of  carbohydrate  starvation, 
relative  or  absolute.  Thus  they  are  found  in  the  urine  during 
absolute  starvation  as   well  as   in   individuals    on  a  pure   fat  and 


1256  PHYSIOLOGY 

protein  diet.      The  two  acids  are  generally  found  associated  in  the 
urine. 

Tlie  presence  of  aceto-acetic  acid  may  be  detected  as  follows  : 

(1)  To  some  urine  add  ferric  chloride  as  long  as  a  precipitate  of  ferric  phos- 
phate continues  to  form.  Filter  tliis  off  and  to  the  filtrate  add  a  few  more  drops 
of  ferric  chloride.    If  the  acid  be  present  a  claret  colour  is  produced. 

(2)  On  heating  -nith  dilute  alkali,  aceto-acetic  acid  is  decomposed,  with 
the  production  of  acetone.  This  may  be  detected  by  its  odour  or  by  distilhng 
off  a  small  proportion  of  the  fluid  and  testing  the  distillate  in  the  following 
ways  : 

(a)  On  the  addition  of  sodium  hydrate  and  iodine  and  warming,  iodoform 
is  formed. 

(6)  Legal's  test.  A  few  drops  of  freshly  precipitated  sodium  nitroprusside 
solution  is  added  and  the  mixture  rendered  alkahne  -nith  sodium  hydrate.  A 
deep  red  colour  is  formed.  On  acidifjnng  ^vith  acetic  acid  this  colour  is  changed 
to  a  reddish  purple. 

CYSTINE.  This  substance,  which  is  a  normal  product  of  the 
hydrolysis  of  proteins,  is  found  as  a  constant  constituent  to  the  amount 
of  half  a  gramme  a  day  in  the  urine  of  certain  individuals.  The  con- 
dition of  cystinuria  represents,  like  alcaptonuria,  an  inborn  error  of 
metabohsm.  It  is  found  in  the  child  and  persists  throughout  life. 
In  such  cases  the  cystine  may  give  rise  to  urinary  deposits  or  even  to  a 
urinary  calculus. 

HOMOGENTISIC  ACID.  This  is  an  aromatic  acid  having  the 
composition  of  dioxyphenyl  acetic  acid.     Its  formula  is  as  follows  : 

OH 


CH2.COOH 
OH 

It  occurs  as  a  constituent  of  the  urine  of  certain  individuals,  who 
are  said  to  be  affected  with  alcaptonuria.  The  urine  of  these  cases  is 
remarkable  for  its  resistance  to  putrefactive  changes.  It  slowly 
darkens  on  exposure  to  the  air,  and  on  the  addition  of  alkali  and 
shaking  with  air  it  becomes  rapidly  brown  or  black.  It  reduces 
Fehling's  solution,  so  that  the  presence  of  sugar  may  be  suspected. 
Such  urine  contains  homogentisic  acid  in  a  quantity  of  3  to  6  grm.  per 
day.  The  amount  of  the  acid  excreted  varies  with  the  protein  food 
taken.  It  seems  that  in  these  cases  the  power  of  the  organism  to 
break  up  tyrosine  and  phenylalanine  is  entirely  absent.  If  either  of 
these  substances  be  administered  by  the  mouth  it  is  converted  almost 
quantitatively  into  homogentisic  acid,  which  appears  in  the  urine. 
Individuals  wnth  alcaptonuria  continue  to  secrete  homogentisic  acid 
during  starvation,  so  that  the  tyrosine  and  phenylalanine  set  free  in 
the  course  of  tissue  disintegration  undergo  the  same  fate  as  when  they 


COMPOSITION  AND  CHARACTERS  OF  URINE        1257 

are  derived  from  the  food.  Alcaptonurians  apparently  suffer  no  ill 
effects  as  a  result  of  their  abnormal  metabolism.  It  seems  that  the 
tyrosine  and  phenylalanine  can  be  absorbed  and  play  their  part  in 
building  up  the  proteins  of  the  tissues,  but  that  the  process  or  ferment 
is  wanting,  which  is  responsible  for  the  further  break-up  of  the  first 
product  of  their  oxidation,  namely, 
homogentisic  acid. 


URINARY  DEPOSITS 
In  addition  to  formed  elements, 
such  as  blood-corpuscles,  bacteria, 
or  pus-cells,  which  may  occur  in 
abnormal  urine,  the  following  de- 
posits may  be  found  : 


Fig.  521.     Various  foim.s  (A  luic  acid 
crystals.     (Frey.) 


(a)  IN  ACID  URINE 

(1)  Amorphous      urates     occur 

generally  as  a  brick-red  amorphous  deposit  thrown  down  as  the  urine 
cools.  It  is  redissolved  on  warming  the  urine,  and  consists  generally 
of  the  quadri-urates.  The  acid  urate  of  sodium  and  of  ammonium 
may  occasionally  occur  in  star-shaped  clusters  of  needles  or  as 
spherules  with  small  crystals  adhering  to  them. 

(2)  Uric  acid.     Whetstone,  dumb-bell,  or  sheaf-like  aggregations  of 

crystals,  generally  deeply  pig- 
mented so  as  to  resemble  cayenne 
pepper  (Fig.  521). 

(3)  Calcium  oxalate  (Fig.  522). 
Colourless,  transparent,  highly  re- 
fractive octahedral  crystals  (enve- 
lope-shaped). Insoluble  in  acetic 
acid,  soluble  in  hydrochloric  acid.  • 

(4)  Ammonium  magnesium 
phosphates  (in  faintly  acid  urine). 
The  crystals  have  been  compared 
to  knife  -  rests  or  coffin  -  lids 
(Fig.  523).  They  are  soluble  in 
acetic  acid. 

(5)  Calcium  liydrogen  plios- 
phate.  CaHPO.,.  These  are  rare. 
They  form  large  prismatic  crystals 

often  arranged  in  rosettes.  Easily  soluble  in  dilute  acetic  acid.  On 
adding  a  solution  of  ammonium  carbonate  the  crystals  are  eaten  awav 
and  form  an  anxorjihous  deposit. 

(6)  Tyrosine,    fine    needles  in  star-shaped  bundles,   and  cystine, 


Fig.  522.  Urinary  deposit,  contriininj^ 
uric  acid,  sodium  urate,  and  calcium 
oxalate. 


1258  PHYSIOLOGY 

in  regular    hexagonal  plates,  may  occur    under    very  rare  circum- 
stances. 

(6)     IN  ALKALINE  URINE 

(1)  The   commonest    precipitate    consists   of   earthy    phosphates, 
amorphous,  easily  soluble  in  dilute  acetic  acid. 

(2)  Ammonium    magnesium    phosphate    or    triple    phosphate    is 
common  in  urine  which  has  undergone  ammoniacal  fermentation. 


Fig.  523.     Deposit  of  '  triple  '  phosphate 
and  ammonium  urate.     (Funke.) 


Fig.  524.     Ammonium  urate. 


(3)  Acid  ammonium  urate  (Fig.  524)  may  also  occur  in  alkaline 
urine.  On  treatment  with  HCl  it  is  dissolved  and  uric  acid  in  crystals 
slowly  separates  out. 

QUANTITATIVE  ESTIMATION  OF  THE  CHIEF  URINARY 
CONSTITUENTS 

It  may  be  useful  here  to  summarise  the  most  trustworthy  methods  which 
are  employed  for  the  estimation  of  the  chief  urinary  constituents.* 

The  TOTAL '  ACIDITY  '  of  the  urine  is  measured  by  titrating  it  against  decinor- 
mal  alkali  in  the  presence  of  an  indicator,  such  as  phenolphthalein.  The  indistinct- 
ness of  the  end-point  is  due  to  the  presence  of  calcium  salts  and  ammonium  saltp. 
Folin  therefore  recommends  that  the  titration  be  carried  out  in  the  pretence  of 
potassium  oxalate,  which  diminishes  the  error. 

Method.  To  25  c.c.  urine  add  15  to  20  grm.  potassium  oxalate  and  1  to  2 
drops  of  phenolphthalein.  Shake  thoroughly  for  one  to  two  minutes,  and  whilst  the 

solution  is  still  cold  from  the  effect  of  the  oxalate,  titrate  with  —  NaOH  until  a 
permanent  pink  remains. 

TOTAL  NITROGEN.  In  all  metabolic  experiments,  the  determination  of  the 
total  nitrogen  of  the  food,  the  urine,  and  the  faeces  is  indispensable.  In  each  case 
Kjeldahl's  method  is  employed.  This  method  depends  on  the  fact  that  all  the 
nitrogenous  substances  met  with  in  the  body,  when  heated  for  a  considerable 
time  with  concentrated  sulphuric  acid,  undergo  oxidation,  the  nitrogen  being 

*  Fuller  details  %vill  be  found  in  Plimmer's  "  Practical  Physiological  Cliemis- 
try,"  from  which  most  of  the  methods  here  given  are  taken. 


COMPOSITION  AND  CHARACTERS  OF  URINE       1259 

finally  converted  into  ammonia.  On  adding  alkali  to  the  mixture  the  ammonia 
is  set  free  from  its  combination  with  the  sulphuric  acid  and  can  be  distilled  off 
and  received  into  a  vessel  containing  a  known  amount  of  decinormal  acid.  By 
titrating  this  acid  after  the  operation  we  can  determine  the  quantity'  of  ammonia 
which  has  been  produced.  To  carry  out  this  method  5  c.c.  of  urine  are  heated 
with  20  c.c.  sulphuric  acid  and  a  small  quantity  of  copper  sulphate  and  potas- 
sium sulphate.  The  copper  sulphate  is  to  aid  the  oxidation  of  the  organic  sub- 
stances, the  potassium  sulphate  is  to  raise  the  boiling-point  of  the  mixture. 
The  boiling  is  continued  for  half  an  hour.  The  flask  is  then  cooled  and 
half  filled  with  distilled  water.  A  special  form  of  distillation  tube  (Fig. 
525)   is  DOW  attached   by  a  rubber  cork  wliich  fits  tightly,    but    just    before 


Fig.  525. 


this  is  done  an  excess  of  strong  caustic  soda  sufficient  to  neutralise  the 
concentrated  sulphuric  acid  is  run  in  under  the  acid.  The  other  end  of  the 
distillation  tube  is  at  once  arranged  to  dip  under  the  surface  of  a  measured 

n 
quantity  of  standard  acid  (e.g.  10  c.c.  tt:  H2SO4),  diluted  with  water,  and  con- 
tained in  a  600  c.c.  Erlenmeyer  flask.     The  flask  is  then  shaken  and  heated. 
In  about  a  quarter  of  an  hour  the  ammonia  is  completely  distilled  off,  and  its 

n 
amount  can  be  determined  by  titrating  the  acid  in  the  flask  with  r^  NaOH, 

methyl  orange  being  used  as  indicator. 

UREA.  The  method  usually  adopted  for  estimating  the  urea  is  that 
devised  by  Hiifner.  It  depends  on  the  fact  that  lu-ea  is  decomposed  by  an  alkaline 
hypobromitc  with  the  production  of  COo  and  nitrogen.  In  the  presence 
of  an  excess  of  alkali  the  COo  is  absorbed  and  the  nitrogen  may  be  collected  and 
measured,  and  serves  as  an  index  of  the  amount  of  urea  present.  The  reaction 
which  occurs  is  as  follows : 

C0(NH2)2  +  SXaBrO  -t-  2NaOH  =  3NaBr  -h  N2  +  NaoCOg  -i-  SU^O 


60  grm. 
1  grm. 

Actually,  however,  only  354-33  c.c.  nitrogen  are  evolved  by  1  grin,  urea 


22-4  litres  =  28  grm. 
372  c.c. 


1260  PHYSIOLOGY 

The  disadvantage  of  this  method  is  that  other  substances,  such  as  ammonia, 
creatinine,  and  uric  acid,  give  off  a  certain  amount  of  their  nitrogen  with  sodium 
hypobromite,  so  that  the  method  is  not  strictly  accurate,  though  enough  so  for 
most  clinical  purposes.  In  actually  carrying  out  the  method  5  c.c.  of  urine  are 
treated  with  25  c.c.  of  freshly  prepared  solution  of  sodium  hypobromite,  and 
the  nitrogen  evolved  is  collected  in  a  graduated  tube  over  water. 

Folin's  Method.  In  Kjeldahl's  method  all  the  nitrogenous  constituents  of 
the  urine  are  converted  into  ammonia  by  boiUng  with  strong  sulphuric  acid. 
This  conversion  occurs  with  extreme  readiness  in  the  case  of  urea,  so  that  by 
using  a  weaker  acid  and  carefully  regulating  the  temperatvu'e  the  hydrolysis  may 
be  confiiied  practically  to  the  vu-ea  itself.  This  is  the  principle  of  Folin's  method 
of  estimating  \irea. 

Five  cubic  centimetres  of  urine  are  measured  into  a  200  c.c.  Erlenmeyer 
flask.  Five  cubic  centimetres  of  concentrated  hydrochloric  acid,  20  grm. 
crystallised  magnesium  chloride,  a  piece  of  paraffin  the  size  of  a  small  hazel 
nut,  and  finally  2  or  3  drops  of  a  1  per  cent,  solution  of  alizarin  red  in  water 
are  added.  A  special  safety  tube  is  then  inserted  into  the  neck  of  the 
flask  and  the  mixture  boiled  until  each  returning  drop  from  the  safety  tube 
produces  a  very  perceptible  bump.  The  heat  is  then  reduced  somewhat,  and  the 
heating  is  continued  for  a  full  hour.  The  alizarin  red  is  used  in  order  to  ensure 
that  the  contents  of  the  flask  do  not  become  alkaline.  At  the  end  of  an  hour 
the  contents  of  the  flask  are  put  into  a  litre  flask  with  about  700  c.c.  water  and 
20  c.c.  of  a  10  per  cent,  sodium  hydrate,  and  the  ammonia  is  then  distilled  off 
into  a  measured  quantity  of  acid.  The  results  obtained  in  this  way  will  give  us 
the  total  amount  of  urea  together  with  any  ammonia  which  was  preformed  in 
the  urine.  It  is  therefore  necessary  also  to  determine  the  amount  of  this  pre- 
formed ammonia. 

ESTIMATION  OF  AMMONIA.  In  Folin's  method  for  the  estimation  of 
ammonia,  this  is  set  free  by  the  addition  of  weak  alkali  (sodium  carbonate)  and  is 
then  removed  from  the  urine  at  ordinary  room  temperature  by  passing  a  strong 
current  of  air  through  the  liquid.  The  issuing  ciu-rent  of  air  carrying  the  ammonia 
passes  through  a  measured  quantity  of  decinormal  acid.  If  the  air  cm-rent  be 
sufficiently  strong,  one  and  a  half  hours  is  sufficient  to  remove  the  whole 
of  the  ammonia  from  25  c.c.  of  urine.  The  decinormal  acid  is  then  titrated 
and  the  amount  of  ammonia  reckoned.  In  carrying  out  the  method  25  c.c. 
of  urine  is  measured  into  a  cyUnder  30  to  45  cm.  high  and  about  a 
gramme  of  sodium  carbonate  and  some  petroleum  (to  prevent  foaming)  are 
added.  The  upper  end  of  the  cyhnder  is  then  closed  by  a  doubly  per- 
forated rubber  stopper  through  which  pass  two  glass  tubes,  only  one  of 
wliich  is  long  enough  to  reach  below  the  surface  of  the  hquid.  The  shorter 
tube,  about  10  cm.  in  length,  is  connected  with  a  calcium  chloride  tube  filled  with 
cotton,  and  this  in  turn  is  connected  with  a  glass  tube  extending  to  the  bottom 
of  a  wide-mouthed  bottle,  capacity  about  500  c.c,  which  contains  20  c.c.  decinormal 
acid  in  200  c.c.  of  water. 

A  more  convenient  method  for  the  estimation  of  ammonia  is  that  originally 
proposed  by  Schiff  and  recently  worked  out  by  Malfatti.  It  depends  on  the  fact 
that  when  a  neutral  solution  of  an  amntonium  salt  is  treated  with  formaldehyde, 
combination  occurs  with  the  formation  of  hexamethylene  tetramine  (iirotropine) 
and  the  liberation  of  a  corresponding  amount  of  acid,  which  can  be  estimated 
by  titrating  with  decinormal  alkali.     The  reaction  which  occurs  is  as  follows  : 

6CH2O  +  2(NH4)2S04  =  6H2O  +  N4(CH2)e  +  2H2SO4. 
Formaldehyde  Hexamethylene  tetramino 

In  carrying  out  this  method  25  c.c.  of  urine  are  measured  by  means  of  a  pipette 


COMPOSITION  AND  CHARACTERS  OF  URINE       12G1 

into  a  flask  or  bcakc-r  aud  (.liluUd  with  fivo  times  its  volume  of  water.  Four  or 
five  drops  of  phenolphllialein  are  then  added  and  deeinormal  sodium  hj'dratc 
is  run  in  until  there  is  a  slight  permanent  pink  colour.  The  amount  of  alkaline 
solution  necessary'  to  produce  this  colom*  is  a  measure  of  the  acidity  of  the  urine. 
Ten  cubic  centimetres  of  formalm,  diluted  with  three  volumes  of  water  and  pre- 
viously neutralised  to  phenolphthalein  with  deeinormal  alkali,  are  then  added. 
The  colour  disappears  owing  to  the  setting  free  of  the  acid  radicals  previously 
combined  with  ammonia.  Deeinormal  alkali  is  then  run  into  the  mixtiu-e  until 
a  permanent  pink  colour  is  again  obtained.  The  number  of  cubic  centimetres 
of  the  deeinormal  alkali  required  in  this  second  case  corresponds  to  the  amomit  of 
deeinormal  ammonia  previously  present  in  the  25  c.c.  of  urine. 

This  method  gives  somewhat  higher  figures  than  the  method  of  Folin  just 
described,  owing  to  the  fact  that  the  small  traces  of  amino-acids,  which  may  be 
present  in  the  lu-ine,  react  to  formalin  in  a  very  similar  way.  The  diflference 
does  not  exceed  10  per  cent.,  so  that  the  method  is  amply  delicate  for  clinical 
purposes. 

CREATININE.  In  Folin's  method  for  the  determmation  of  creatinine,  which  is 
now  muversally  employed,  advantage  is  taken  of  the  colour  reaction  given  by 
creatinine  (and  by  no  other  normal  lu-inary  constituent)  wdth  picric  acid  in  alkaline 
solution  (Jaffe's  reaction),  the  colour  being  compared  with  that  of  a  standard 
potassium  bichromate  solution.  The  reagents  employed  are  deeinormal  potassium 
bichromate  contaming  24-55  grm.  per  litre,  saturated  picric  acid  solution 
containing  about  12  grm.  per  litre,  and  a  10  per  cent,  solution  of  sodium  h3-drate. 
For  the  comparison  of  the  coloiu's  a  Duboseq  colorimeter  is  employed. 

Ten  cubic  centimetres  of  urine  are  measured  into  a  500  c.c.  flask ;  15  c.c.  of 
picric  acid  and  5  e.c.  of  sodium  hydrate  are  then  added  and  the  mixture  allowed 
to  stand  for  five  minutes.  Some  of  the  potassium  bichromate  solution  is  placed 
into  one  of  the  cylinders  of  the  colorimeter  and  its  depth  accurately  adjusted  to 
the  8  mm.  mark.  At  the  end  of  five  minutes  the  contents  of  the  500  c.c.  flask 
are  diluted  up  to  500  c.c.  with  water  and  some  of  the  mixture  placed  into  the 
other  eylhider  of  the  colorimeter,  and  the  two  colours  are  then  compared.  The 
calculation  of  the  results  is  very  simple.  If,  for  example,  it  is  found  that  it 
takes  9-5  mm.  of  the  unknown  m-ine  picrate  solution  to  equal  the  8  mm.  of  the 
bichromate,  then  the  10  c.c.  of  urine  contains 

8*1 
10  X  —  =  8-4  mg.  creatinine. 
9-5  ^ 

ESTIMATION  OF  URIC  ACID.     The  best  method  for  this  purpose  is  a  slight 
modification  by  Folin  of  the  method  devised  by  Hopkins. 
For  this  method  the  following  reagents  are  required  : 

(1)  A  solution  of  ammonium  sulphate,  m-anium  acetate,  and  acetic  acid,  made 

up  as  follows  :  500  grm.  ammonium  sulphate,  5  grm.  uranium  acetate,  and 
60  c.c.  10  per  cent,  acetic  acid  are  dissolved  in  050  c.c.  water.  The  volume 
of  this  solution  is  almost  exactly  1000  c.c. 

(2)  Ten  per  cent,  ammonium  sulphate  solution. 

(3)  —  potassium  permanganate  solution  made  by  dissolving  1-581  grm.  pure 

potassium  permanganate  in  one  litre  of  water  ;  1  c.c,  =  -00375  grm.  uric 
acid. 

Measure  200  c.c.  urine  with  a  pipette  into  a  500  c.c.  flask  and  add  50  c.c.  of 
the  ammonium  sulphate  and  inanium  acetate  reagent.  Mix  the  solutions  and 
allow  to  stand  for  about  half  an  hour  so  as  to  allow  the  precipitate  to  settle. 
This  precipitate  contains  a  nmeoid  substance  (and  phosphates)  which,  if  not 


1262  PHYSIOLOGY 

thus  removed,  renders  the  subsequent  filtration  and  washing  of  the  ammonium 
urate  precipitate  very  slow.  Filter  oflf  the  supernatant  liquid  through  a  dry 
filter  into  a  dry  vessel,  and  measure  out  125  c.c.  (=  100  c.c.  m'ine)  of  this  with 
pipettes  into  a  beaker.  Add  5  c.c,  concentrated  ammonia,  mix  well,  and  allow 
to  stand  covered  with  paper  for  twelve  to  twenty-foiu-  hours. 

Carefully  decant  the  supernatant  liquid  upon  a  filter,  wash  the  precipitate 
of  ammonium  vu-ate  on  to  the  filter  with  10  per  cent,  ammonium  sulphate,  and 
wash  this  once  or  twice  with  the  same  reagent  to  remove  the  chlorides  as 
completely  as  possible. 

Remove  the  filter  from  the  fimnel,  open  it,  and  with  a  fine  stream  of  water 
wash  the  ammonium  m-ate  precipitate  into  a  beaker.  To  the  ammonium  urate 
precipitate,  suspended  in  about  100  c.c.  water,  add  15  c.c.  strong  sulphuric  acid 
and  titrate  at  once  without  cooling  with  the  potassium  permanganate  solution. 
At  first  every  smaU  addition  of  the  permanganate  is  decolorised  before  it  diffuses 
through  the  liquid,  but  towards  the  end  the  decolorisation  is  slower"  and  the  per- 
manganate should  be  added  two  drops  at  a  time  mitil  a  faint  pink  colour  is  seen 
throughout  the  whole  solution.  The  amount  of  uric  acid  can  then  be  calculated, 
1  c.c.  of  the  permanganate  solution  being  equivalent  to  -00375  grm.  uric  acid. 

CHLORIDES.  The  clilorides  of  urine  are  estimated  by  Volhard's  method. 
The  principle  of  this  m.ethod  consists  in  precipitating  the  chlorides  by  excess  of 
a  standard  solution  of  silver  nitrate  in  the  presence  of  nitric  acid.  The  excess 
of  silver  is  then  estimated  in  an  ahquot  part  of  the  fUtrate  with  a  solution  of 
potassium  or  ammonium  sulphocyanate  wMch  has  been  previously  standardised 
against  the  silver  solution,  a  ferric  salt  being  used  as  indicator. 

The  following  solutions  are  required  : 

(1)  Standard  silver  nitrate  solution  either  —  or  so  that  1  c.c.  corresponds  to 

•01  grm.  NaCl. 

(2)  Potassium  sulphocyanate  solution  (8  grm.  per  litre). 

(3)  Pure  HNO3  free  from  chlorides. 

(4)  A  saturated  solution  of  iron  alum. 

The  potassium  sulphocyanate  solution  must  be  standardised  against  the 
sulphocyanate  solution.  This  is  carried  out  as  follows  :  Place  10  c.c.  AgNOy 
solution  with  a  pipette  in  a  beaker,  add  5  c.c.  pure  HNO3,  5  c.c.  iron  alum  solution, 
and  80  c.c.  water.  Now  run  in  the  sulphocyanate  solution  from  a  biu-ette  until 
a  permanent  red  tinge  is  obtained.  Note  the  amount  required  for  the  10  c.c. 
AgNOs  solution. 

The  method  of  analysis  is  carried  out  as  follows  :  Place  10  c.c.  urine  in  a  100  c.c. 
measuring  flask  with  a  pipette.  Then  add  about  4  c.c.  pure  nitric  acid  and  10  or 
20  c.c.  with  a  pipette  of  the  standard  silver-nitrate  solution.  Now  fill  up  to  the 
mark  with  distilled  water,  mix  thorouglaly,  and  filter  into  a  dry  vessel  through  a 
dry  paper.  Take  exactly  50  c.c.  of  the  filtrate  with  a  pipette  and  titrate  witli  the 
sulphocyanate  solution  until  a  permanent  red  colour  is  obtained,  iron  alum 
liaving  been  added  before  the  titration  is  commenced.    Calculation  of  results  : 

50  c.c.  filtrate  =  S  c.c.  KCNS 

.-.  100  c.c.       „      =  2^  c.c.     „ 

Now  X  c.c.  KCNS  =  10  c.c.  AgNOg 

ot-                          10  X  28  .   ,,„ 
.-.  2/S'c.c.       „       = AgNOg 

X 

This  is  the  excess  not  utilised  to  precipitate  the  chlorides 

.«.  (20 \  =  amount  of  AgNOg  solution  used. 

Hence  NaCl  in  grammes  per  10  c.c.  in  the  volume  passed  in  twenty -four  hours. 


COMPOSITION  AND  CHARACTERS  OF  URINE       1263 

ESTIMATION  OF  PHOSPHATES.  The  method  depends  upon  the  precipitation 
of  all  the  phosphates  by  a  standard  solution  of  uranium  acetate  or  uranium  nitrate 
m  the  presence  of  sodium  acetate  and  acetic  acid  as  (rr02)HP04.  The  deter- 
mination of  the  end-point,  when  soluble  uranium  salt  is  in  solution,  is  shown 
by  means  of  potassium  ferrocyanide,  or  by  cochineal  tincture,  which  becomes 
green. 

The  following  reagents  are  required  : 

(1)  Acid  sodium  acetate  solution  (100  grra.  NaAc,  30  grm.  HAc,  1000  c.c.  HgO). 

(2)  Cochineal  tincture  (5  grm.  cochineal  extracted  for  several  days  with  150  c.c. 

alcohol  and  100  c.c,  water  and  then  filtered). 

(3)  Standard  mranium  solution  (1  c.c.  =  -005  grm.  P2O6  or  5  mg.). 

This  must  be  prepared  by  standardising  against  a  standard  phosphate  solution- 
Generally  sodium  phosphate  is  employed  ;  about  12  grm.  are  weighed  out  and 
dissolved  in  1000  c.c.  water  ;  50  c.c.  of  this  solution  are  evaporated  to  dryness, 
incinerated,  and  weighed  as  p\Tophosphate.  From  the  weight  of  this  the  amount 
of  P2O6  in  50  c.c.  can  be  calculated  and  the  remainder  of  the  solution  can  be 
diluted,  so  that  50  c.c.  contain  0-1  grm.  P2O6.  It  is  simpler  to  use  acid  potassium 
phosphate,  KH2PO4,  which  can  be  weighed  directly  and  dissolved  in  water,  so 
that  50  c.c.  contain  01  grm.  P2O5.  Fifty  cubic  centimetres  of  this  solution 
are  titrated  with  the  iu"anium  solution  (36  grm.  in  one  litre)  in  the  manner 
described  below,  and  the  uranium  solution  is  then  diluted  so  that  1  c.c.  = 
5  mg.  P2O6. 

The  method  of  analysis  is  carried  out  as  foUows :  Place  50  c.c.  urine  with  a 
pipette  in  a  100  c.c.  beaker,  add  5  c.c.  acid  sodium  acetate  solution  and  a  few 
drops  of  cochineal  tincture.  Heat  the  urine  to  boUing  and  run  in  slowlj'  the 
standard  uranium  acetate  solution  from  a  burette  as  long  as  a  precipitate  is 
formed.  Again  heat  to  boiling  and  add  the  uranium  solution  drop  by  drop, 
until  the  red  colour  is  changed  to  green.  This  end-point  can  also  be  tested  by 
taking  out  a  drop  and  placing  it  in  contact  with  a  drop  of  potassium  ferrocyanide 
solution  or  a  little  heap  of  finely  powdered  substance  on  a  white  piece  of  porcelain. 
A  browii  colour  or  precipitate  is  formed  when  excess  of  soluble  viranium  salt  is 
present  in  the  solution.  (A  few  more  drops  may  be  required  to  reach  this  point 
than  to  tm-n  the  cochineal  green.) 

The  principle  of  the  estimation  of  sulphates  has  already  been  described.  It 
is  not  advisable  to  attempt  these  volumetrically. 


SECTION  II 
THE  SECRETION  OF  URINE 


With  the  single  exception  of  hippuric  acid  all  the  constituents 
of  the  urine  are  formed  in  parts  of  the  body  other  than  the  kidneys. 
Extirpation  of  both  kidneys  leads  to  an  accumulation  of  these  specific 
urinary  constituents  in  the  blood  and  tissues.  The  work  of  the  kidney 
is  therefore  confined  to  an  excretion  of  preformed  constituents. 
Considered  from  a  broad  standpoint,  the  function  of  this  organ  is  the 

preservation  of  the  normal  com- 
position of  the  circulating  blood. 
Whenever  the  latter  contains  an 
abnormal  constituent  or  any  of  its 
normal  constituents  are  present  in 
abnormal  quantities,  the  kidney 
excretes  the  substance  in  question 
until  the  composition  of  the  blood  is 
restored.  We  have  to  determine 
the  conditions  which  influence  the 
quantity  and  quality  of  the  urine 
secreted  by  the  kidneys,  and  to 
ascribe  to  each  element  in  these 
organs  its  proper  share  in  the  total 
work  of  the  kidney. 

In  no  other  organ  of  the  body 
are  our  views  as  to  function  so  inti- 
mately dependent  on  our  know- 
ledge of  structure  as  in  the  kidney. 
This  organ  is  a  branched  tubular 
gland  consisting  in  man  of  ten 
to  fifteen  nearly  equal  divisions, 
knowni  as  the  Malpighian  pyramids. 
In  certain  animals,  such  as  the  rabbit  and  rat,  only  one  pyramid  is 
present.  It  is  divided  into  an  outer  portion  or  cortex,  an  inner  portion, 
the  medulla,  and  between  these  the  '  boundary  layer,'  containing  the 
larger  branches  of  the  renal  blood-vessels  (Fig.  526).  From  the  outer 
boundary  of  the  Malpighian  pyramids  of  the  medulla  a  number  of 
processes,  the  medullary  rays,  pass  out  into  the  cortex  towards  the 

1264 


Caoiat. 

Fig.  526.     Section  of  human  kidney 
(Cadiat.) 
a,  cortex  ;  h,  nudulla  or  Malpighian 
pyramids  ;    c,    papilla  ;     d,    ureter  ; 
e,  e,  boundary  zone. 


THE  SECRETION  OF  URINE 


1265 


surface  of  the  kidney.  All  parts  of  the  kidney  are  made  up  of  branched 
tubules  embedded  in  scanty  connective  tissue  and  richly  supplied  with 
blood-vessels.  Each  tubule  begins  by  a  blind  dilated  extremity  in  the 
cortex,  known  as  Bowman's  capsule,  which  surrounds  a  bunch  of  capil- 
lary blood-vessels,  the  glomerulus,  the  two  together  forming  the  Mal- 
pighian  capsule.  From  Bowman's  capsule  a  short  neck  leads  into  a 
proximal  convoluted  tubule,  and  this  into  a  U-shaped  portion  which 


Cortex 


U  Bouudary  zoue 


Medulla 


Fio.  527. 


Diagram  showing  course  of , urinary  tubules,  and  the  distribution 
of  the  blood-vessels.     (From  Yeo.) 


passes  down  in  a  medullary  ray  into  the  underlying  portion  of  the 
medulla,  and  consists  of  straight  descending  and  ascending  limbs  and 
the  loop  of  Heiile.  The  ascending  limb  passes  into  a  distal  convoluted 
tubule,  and  this  by  a  'junctional  tubule'  joins  with  a  number  of 
others  to  form  a  straight  '  collecting  tubule.'  Several  of  these  unite 
to  form  the  papillary  ducts,  which  open  on  the  surface  of  the  papilla 
in  the  expanded  part  of  the  renal  duct  or  ureter  (Fig.  527).  The  whole 
tubule  consists  of  epithelium  lying  on  a  basement  membrane  ;  the 
epithelium  varies  in  structure  in  different  parts  of  the  tubule.  The 
bunch  of  glomerular  capillaries  is  covered  with  a  very  thin  layer  of  endo- 
thelial cells,  and  a  similar  layer  forms  the  Uning  of  Bowman's  capsule. 
The  convoluted  tubules  contain  cells  which  are  roughly  cubical  or 
cyhndrical  in  cross-section,  but  do  not  present  very  definite  cell  out- 
lines. These  cells,  which  are  similar  in  the  two  sets  of  convoluted 
tubules,  have  long  been  distinguished  as  '  rodded  epithelium  '  (Fig.  528) 
on  account  of  the  ease  with  which  a  radial  disposition  of  rods  orgranules 
is  demonstrated  in  their  protoplasm.     As  ordinarily  prepared,  the 

80 


1266  PHYSIOLOGY 

free  margin  of  these  cells,  where  they  abut  on  the  lumen,  is  irregular. 
This  appe  arance  is  due  to  the  readiness  with  which  the  cells  undergo 
alteration  under  the  influence  of  different  fixing  reagents,  especially 


Fig.  528.     A  portiirn  ,,l  a 


<jii\  (ilutcd  tubule  with  '  rodded  '  epithelium. 
(Heidexhain.) 


of  such  as  contain  water.  When  properly  fixed  it  is  seen  that  the 
rodded  structure  as  described  by  Heidenhain  is  due  to  rows  of  gxanules 
arranged  vertically  to  the  basement  membrane.  Moreover  the  free 
margin  of  the  cells,  instead  of  being  irregular,  consists  of  a  well-marked 
striated  border,  formed  of  a  number  of  very  fine  hairs  closely  set 
together  and  springing  from  a  row  of  granules  in  the  peripheral  part 
of  the  cell  (Fig.  529).    The  hairs,  which  make  up  the  striated  border 


FiG.  529.     Cross-R(ctiiin<  (it  ((involuted  tubules  from  kidn(\  '  i      ii 
A,  during  slight  .secretion  ;   B,  during  maximal  secretion. 


(Saver.) 


(sometimes  called  the  '  brush  border '),  have  not  been  observed  to 
present  ciUary  movement,  and  are  probably  comparable  with  the 
similar  structures  found  clothing  the  free  border  of  the  epithelium  of 
the  intestinal  villus.     Such  cells  are  characteristic  featui-es  of  the 


THE  SECRETION  OF  URINE  1267 

epithelium  lining  the  urinary  organs  in  all  types  of  animals,  and  are 
well  marked  in  the  nephridia  of  worms.  Besides  these  rows  of 
granules  other  granules  are  found,  especially  towards  the  free  margin 
of  the  cell  and  round  about  the  nucleus.  Some  of  the  granules  appear 
to  be  of  a  fatty,  others  of  a  protein  character. 

The  descending  limb  of  Henle's  loop  is  narrow,  and  possesses 
flattened  epithelial  cells,  while  the  ascending  limb  presents  an  epithe- 
lium similar  to  that  of  the  convoluted  tubules,  but  with  less  marked 
striation.  The  junctional  and  collecting  tubules  are  lined  with 
cubical  or  columnar  cells  with  a  clear  protoplasm.  The  marked 
differences  between  the  structure  of  these  various  parts  point  to  a 
differentiation  of  function  and  division  of  labour  among  them  in  the 
preparation  of  the  fully  formed  urine.  This  conclusion  is  borne  out 
by  a  study  of  the  blood-supply  of  this  kidney.  The  large  renal  artery 
divides  in  the  pelvis  into  four  or  five  branches,  which  pass  up  to 
the  boundary  zone  and  there  give  off  arteries  in  different  directions  ; 
those  which  run  towards  the  surface  are  the  interlobular  arteries. 
Each  of  these,  which  is  an  end-artery  presenting  no  anastomoses  with 
its  fellows,  gives  off  on  all  sides  short  wide  branches,  which  pass 
to  the  glomeruli  and  constitute  the  vasa  afferentia  of  these  bodies. 
Each  vas  afferens  has  a  thick  muscular  wall.  The  glomerulus  itself 
consists  of  a  number  of  anastomosing  wide  capillaries  invested  by  an 
extremely  thin  wall,  which  is  sometimes  said  to  consist  simply  of  a 
protoplasmic  film  devoid  of  nuclei.  The  glomerular  capillaries  are  col- 
lected together  to  form  an  efferent  vessel,  the  vas  efferens,  which  is 
narrower  than  the  vas  afferens,  but,  Like  the  latter,  presents  a  well- 
marked  muscular  coat.  The  vas  efferens  breaks  up  again  into  a  second 
set  of  capillaries,  which  ramify  around  the  tubules  of  the  cortex  and 
communicate  with  a  similar  network  round  the  tubules  of  the  medulla. 
The  medullary  p\'Tamids  are  also  provided  with  blood  by  a  plexus  of 
capillaries  taking  their  origin  from  little  bunches  of  vessels,  the  vasa 
recta  {v.  Fig.  527),  which  leave  the  concave  side  of  the  arterial  arches  of 
the  boundary  zone  to  run  towards  the  papilla,  and  receive  also  a  few 
vessels  which  spring  from  the  vasa  afferentia  of  the  cortical  vessels. 
From  the  capillaries  of  the  tubules  the  blood  is  collected  again  into 
veins,  which  leave  the  kidney  partly  by  the  cortex  and  capsular  vessels, 
partly  by  large  venous  trunks  which  join  to  form  the  renal  vein  at  the 
hilum  of  the  kidney.  The  kidney  is  richly  supplied  with  nerves,  which 
are  chiefly  distributed  to  the  muscular  walls  of  its  blood-vessels.  Some 
authors  have  described  a  fine  nerve-plexus  surrounding  the  tubules  and 
sending  branches  between  and  into  the  cells  of  the  convoluted  tubules 
themselves. 

The  main  points  in  the  above  description  of  the    structure  of 
the  kidney  were  made  out  by  Bowman  in  1840,  and  suggested  the 


1268  PHYSIOLOGY 

theories  of  urinary  secretion  both  of  Bowman  and  of  Ludwig  (1844), 
theories  which  have  furnished  the  basis  of  all  our  subsequent  investiga- 
tion of  the  subject.  Both  observers  appreciated  the  great  difference 
between  the  membrane  covering  the  glomerular  loop  and  the  lining 
membrane  of  the  tubule,  and  both  drew  attention  to  the  difEerence  in 
the  circulation  in  these  two  portions  of  the  kidney.  The  glomerular 
capillaries,  supplied  with  blood  through  a  short  wide  artery  and  drained 
by  an  efferent  vessel  smaller  than  the  afferent,  would  represent  a  region 
of  very  high  capillary  blood  pressure,  whereas  the  pressure  in  the  capil- 
laries surrounding  the  tubules  must  be  low  and  similar  to  that  in  other 
capillary  regions.  Bowman  therefore  suggested  that  the  urine  consisted 
of  two  parts,  namely,  one  part  containing  the  water  and  salts  produced 
by  a  process  of  filtration  through  the  walls  of  the  glomerular  capillaries, 
and  another  part,  containing  the  specific  urinary  constituents  urea, 
uric  acid,  &c.,  secreted  by  the  cells  probably  of  the  convoluted  tubules. 
To  Ludwig,  on  the  other  hand,  it  seemed  possible  at  first  to  account  for 
the  whole  process  of  formation  of  urine  without  the  assumption  of  any 
active  intervention  on  the  part  of  the  cells  of  the  tubules.  He  im- 
agined that  the  whole  of  the  urinary  constituents  passed  from  the 
blood  to  the  urinary  tubule  in  the  glomerulus  by  a  process  of  filtration. 
The  glomerular  transudate  would  represent  therefore  a  very  dilute 
urine  containing  the  crystalloids  of  the  blood  in  the  same  concentra- 
tion as  in  the  blood  and  with  no  more  urea  than  the  blood  itself  con- 
tained. The  great  difference  in  urea  content  between  the  blood 
and  the  fully  formed  m-ine  he  ascribed  to  a  process  of  concentration 
taking  place  in  the  fluid  in  its  passage  through  the  tubules,  in  which 
water  and  certain  of  the  salts  were  reabsorbed,  a  process  of  re- 
absorption  conditioned  by  the  difference  in  protein  content  between 
the  urine  within  the  tubules  and  the  lymph  under  low  pressure  on 
the  outside  of  the  tubules.  We  know  now  that  in  its  original  form 
the  theory  of  Ludwig  is  untenable.  If  a  process  of  concentration 
takes  place  within  the  tubules  it  must  involve  the  performance  of 
work  by  the  cells  lining  these  tubules,  and  could  not  take  place  as 
a  result  of  mere  differences  of  colloid  content  between  the  two  fluids. 
It  was  shown  long  ago  by  Hoppe-Seyler  that,  if  urine  be  dialysed 
against  serum,  a  passage  of  water  takes  place,  not  from  urine  to  serum, 
but  from  serum  to  urine,  i.e.  the  latter  is  much  more  concentrated  than 
the  former.  The  movement  of  water  from  one  fluid  to  another 
through  a  colloid  membrane  depends  on  the  relative  osmotic  pressures 
of  the  two  fluids,  and  this  in  turn  is  determined  by  the  molecular  con- 
centration of  the  two  fluids.  It  is  easy  to  estimate  the  molecular  con- 
centration of  any  sample  of  serum  or  urine.  The  method  which  is 
most  convenient  is  to  determine  the  depression  of  freezing-point  in  the 
two  fluids.  Whereas  serum  ordinarily  freezes  at  —  0-50°  C.  to  —  0-59°  C  , 


THE  SF.CRETION  OF  URINE  12G0 

the  freezing-point  of  urine  is  generally  lower  and  may  vary  from 
this  figure  to  as  much  as  —  4-5°  C.  For  the  production  therefore  of 
urine  from  blood-plasma,  a  certain  amount  of  work  has  to  be  done, 
and  the  seat  of  this  work  we  can  locate  only  in  the  cells  of  the  kidney. 
We  may  determine  the  minimum  work  necessary  to  form  a  certain 
amount  of  urine  of  a  given  concentration  by  measuring  the  amount  of 
heat  that  must  be  imparted  to  the  blood-plasma  in  order  to  reduce  it  to 
the  same  concentration  and  volume,  or  we  can  calculate  it  if  we  know 
the  freezing-points  of  the  two  fluids.  A  depression  of  freezing-point 
A  =  —  1°  C.  corresponds  to  an  osmotic  pressure  of  122-7  metres  of 
water.  To  concentrate  100  c.c.  of  a  saline  fluid  such  as  urine  so  as  to 
halve  its  bulk  and  double  its  depression  of  freezing-point,  e.g.  from 
—  1°  C.  to  —  2^  C,  would  therefore  require  the  expenditure  of  work 
equivalent  to  that  which  would  be  required  to  compress  100  c.c.  of  a 
gas  at  a  pressure  of  122*7  metres  of  water  to  half  its  bulk. 

The  abandonment  of  Ludwg's  view  as  to  the  mechanism  of  the 
concentration  does  not,  however,  place  his  theory  out  of  court.  The 
question  will  still  have  to  be  discussed  whether  the  chief  object  of 
the  tubules  is  the  concentration  of  the  fluid  produced  in  the  glomeruli, 
or  whether  they  add  to  this  fluid  by  a  further  secretory  process,  or 
whether  they  may  not  possibly  possess  both  functions  and  in  their 
various  parts  alter  the  fluid  flowing  through  them  either  by  addition 
or  by  withdrawal  of  water  or  dissolved  constituents.  The  common 
point  in  the  two  theories  is  the  sharp  distinction  which  is  drawn 
between  the  nature  of  the  glomerular  activity  and  the  nature  of  the 
activity  of  the  tubules.  The  questions  which  we  have  to  decide  by 
experiment  are  : 

(1)  The  nature  of  the  glomerular  activity  and  the  conditions  which 
determine  the  amount  of  fluid  formed  by  the  glomeruli,  and  especially 
whether  the  energy  required  for  the  formation  of  the  glomerular  fluid 
is  furnished  by  the  heart  through  the  blood  pressure  within  the  capil- 
laries or  by  the  endothelium  covering  these  capillaries. 

(2)  The  function  of  the  tubules,  whether  they  secrete  or  absorb, 
and  what  part  is  played  in  these  processes  by  the  various  segments  of 
the  tubules  which  difier  so  widely  in  their  histological  characters. 

THE  SECRETION  OF  WATER  AND  SALTS.  FUNCTIONS 
OF  THE  GLOMERULI 
It  is  generally  assimied,  as  the  best  explanation  of  known  facts 
with  regard  to  the  secretion  of  urine,  that  a  watery  exudation  free 
from  protein  is  formed  in  th'e  glomeruli,  and  that  this  becomes  con- 
centrated on  its  way  through  the  tubules  either  by  the  absorption  of 
water  and  certain  salts  or  by  the  secretion  and  addition  of  urea,  uric 
acid,  &c..  as  well  as  such  salts  as  acid  phosphates.     As  to  the  nature 


1270  PHYSIOLOGY 

of  the  glomerular  functions  two  opinions  have  been  held.  According 
to  the  Ludwig  school  the  process  is  one  simply  of  filtration,  in  which, 
under  the  pressure  of  the  blood  in  the  glomerular  capillaries,  the 
water  and  crystalloid  constituents  of  the  plasma  are  filtered  through 
the  glomerular  epithelium,  leaving  behind  the  protein  constituents. 
According  to  Heidenhain  the  process  cannot  be  regarded  as  one  simply 
of  filtration,  but  involves  the  secretory  activity  of  the  glomerular 
epithelium.  If  the  glomerular  urine  is  a  filtrate  it  must  resemble 
blood  plasma  in  practically  all  particulars  except  its  protein  content, 
since  the  blood  pressure,  which  is  the  only  force  causing  filtration,  is 
too  small  to  effect  any  appreciable  separation  of  salts.  On  the  other 
hand,  a  certain  minimum  difference  of  pressure  between  the  two  sides 
of  the  membrane  must  be  present  in  order  to  separate  the  colloids 
from  the  other  constituents  of  the  plasma.  We  have  seen  in  chapter  iv 
(p.  158)  that  in  order  to  produce  a  filtrate  containing  only  water  and 


pressure  '~~--^ 


■j  pressure 


Fig.  530. 

salts  from  serum  a  minimum  difference  of  pressure  of  30  mm.  Hg  is 
necessary,  corresponding  to  the  osmotic  pressure  of  the  colloidal  con- 
stituents of  the  blood-plasma  or  serum.  Thus  in  order  to  produce  a  fil- 
trate, free  from  protein,  from  the  blood-plasma  circulating  through  the 
glomerular  capillaries,  the  pressure  of  the  urine  in  the  tubules  and  ureter 
must  always  be  at  least  30  mm.  lower  than  the  pressure  of  the  blood  in 
the  glomeruli.  A  direct  determination  of  the  latter  figure  is  not  possible. 
The  anatomical  arrangements  are  such  as  to  bring  this  pressure  up  to  a 
high  point.  Not  only  are  the  vasa  afferentia  very  short,  but  the  vasa 
efferentia  are  only  two-thirds  of  the  diameter  of  the  vasa  afferentia. 
Moreover  the  suddeji  increase  of  bed  which  ensues  as  the  blood  passes 
from  the  vas  afferens  to  the  bundle  of  capillaries  must  itself  cause  a 
rise  of  pressure  in  the  latter,  due  to  the  transformation  of  the  kinetic 
energy  of  the  moving  fluid  into  the  statical  energy  represented  by 
pressure  on  the  walls  of  the  vessels. 

Tliis  point  can  be  rendered  clearer  by  tlie  following  considerations.  If  fluid  is 
flowing  in  a  tube  of  continuous  bore  ah  (Fig.  530)  there  will  be  a  continuous  fall  of 
pressure  from  a  to  h.  If,  however,  in  tiie  tube  ahc  the  segment  h  be  of  much  greater 
(hameter  than  the  segments  a  and  c,  althougli  wliile  the  fluid  is  at  rest  the  pressures 
will  be  equal  at  all  points  of  the  .system,  as  soon  as  the  fluid  moves  from  a  to  c, 
although  there  is  a  fall  of  pressure  between  a  and  c,  a  manometer  attached  to  h  may 


THE  SECRETION  OF  TRINE  1271 

show  an  actual  greater  pressure  than  a  manometer  inserted  at  a.  Fluid  is  flowing 
from  a  place  of  lower  to  a  place  of  higher  pressure.  The  apparent  paradox  is  due 
to  the  fact  that  the  energy  causing  the  fluid  to  move  from  a  to  6  is  of  two  kinds. 
It  equals  hnv~  +  P,  i.e.  is  represented  by  the  kinetic  energy  of  the  moving  mass  of 
fluid  as  well  as  the  diff'erence  of  pressure  between  any  two  points  of  the  tube. 
The  total  energy  will  diminish  continuously  from  a  to  c,  and  is  used  in  overcoming 
the  resistance  of  the  system.  We  may  say  then  that  the  sum  of  these  two, 
namely,  ^mv"  +  P,  is  greater  at  a  than  b,  and  is  greater  at  b  than  c  ;  but  as  the  fluid 
passes  from  the  narrow  tube  a  into  the  wide  tube  b  there  is  a  sudden  fall  of  its 
velocity  and  a  consequent  diminution  of  the  factor  ^mv^.  In  order  to  pro- 
vide for  a  continuous  fall  in  the  total  energy  of  the  fluid,  namely,  Imir  +  P, 
the  diminution  in  the  factor  Imv-  must  cause  a  corresponding  increase  in  the 
factor  P,  i.e.  in  the  lateral  pressure  exercised  by  the  fluid  on  the  vessel  wall. 
As  the  total  diameter  of  the  bed  of  the  stream  in  the  capillaries  may  be  twenty 
times  that  of  the  bed  in  the  vas  afferens  the  velocity  of  the  blood  in  these  capillaries 
will  be  only  one-twentieth  of  that  in  the  artery  and  the  kinetic  energy  of  the 
blood  only  one  four-hundredth.  It  is  possible  therefore  that  the  pressure  exer- 
cised by  the  blood  on  the  walls  of  the  capillaries  may  be  even  greater  than  that 
in  the  interlobular  arteries,  and  this  efi"ect  will  be  still  further  aided  by  the  narrow 
diameter  of  the  vas  effercns.  Although  therefore  the  pressure  in  the  ordinary 
capillaries  of  the  body  is  probably  not  greater  than  20  to  30  mm.  Hg,  the 
glomerular  capillaries  might  present  a  prcssviro  little  inferior  to  that  in  the 
main  arteries  of  the  body. 

The  pressure  in  the  ureter  is  under  normal  circumstances  ap-  . 
proximately  nil,  whereas  that  in  the  glomerular  capillaries  is  probably 
not  more  than  20  mm.  Hg  below  that  in  the  main  arteries  of  the 
body,  so  that  there  is  a  difference  of  pressure  on  the  two  sides  of  the 
membrane  more  than  sufficient  to  cause  a  constant  filtration  of  a 
protein-free  fluid  from  the  blood-plasma  coursing  through  these 
capillaries.  On  raising  the  pressure  on  the  tubule  side  the  filtration 
ought  to  come  to  an  end  when  the  pressure  approaches  a  figure  which 
is  30  to  40  mm.  below  that  in  the  glomerular  capillaries.  A  number 
of  observers  have  found  that  urinary  secretion  ceases  when  the  blood 
pressure  falls  to  between  40  and  50  mm.  Hg.  The  urinary  secretion 
can  be  stopped  by  raising  the  pressure  in  the  tubules  by  means  of 
ligature  of  the  ureter.  On  applying  the  ligature  the  secretion  con- 
tinues for  a  time  until  the  pressure  in  the  ureter  rises  up  to  a  certain 
point,  when  the  secretion  comes  to  an  end.  In  one  experiment  the 
following  pressures  were  obtained  in  a  dog  which  was  secreting  urine 
copiously  under  the  action  of  diuretin.  Manometers  were  connected 
both  with  the  carotid  artery  and  with  the  ureters  so  that  no  outflow 
of  urine  was  possible  : 

Arterial  pressure  Uretir  pressure 

140  ....  72 

138  ....  92 

133  ....  88 

In   this   experiment  therefore  secretion  came  to  an  end  with  a 


1272  PHYSIOLOGY 

difference  of  pressure  between  ureter  and  arteries  of  between  40  and 
50  mm.  Hg. 

The  absolute  pressure  attained  within  the  ureter  in  any  given  experiment 
after  ligature  of  these  tubes  will  vary  with  several  factors.  In  the  first  place, 
if  the  minimum  secreting  pressure  is  really  conditioned  by  the  colloid  content 
of  the  blood-plasma,  it  will  be  less  the  smaller  the  proportion  of  colloids  in  the 
plasma.  In  some  experiments  (Magnus)  a  flow  of  iirine  was  observed  with  a  blood- 
pressure  as  low  as  18  mm.  Hg,  but  in  this  case  the  blood  was  extremely  dilute 
as  the  result  of  the  continuous  injection  into  the  blood-vessels  of  normal  salt 
solution.  Barcroft  and  Knowlton  have  sho\Mi  that  the  diuresis  brought  about 
by  injection  of  saline  (Ringer's)  solution  is  inhibited  by  mixing  with  the  saline 
fluid  colloids,  such  as  gelatin  and  gum,  which  possess  an  osmotic  pressure. 
Colloids  such  as  starch,  with  no  measurable  osmotic  pressure,  have  no  such 
effect. 

On  the  other  hand,  the  m-eters,  or  at  any  rate  the  urinary  tubules,  cannot  be 
regarded  as  absolutely  water-tight.  Not  only  are  the  cells  of  these  tubules 
capable  of  taking  up  fluid,  but  it  is  probable  that  at  high  presswes  a  certain 
amount  of  actual  filtration  takes  place  between  these  cells.  This  process  of 
reabsorption  will  tend  to  diminish  the  actual  pressiu-e  of  the  fluid  in  the  ureters, 
so  that  the  secretion  of  urine  may  apparently  come  to  a  standstill  when  there  is 
still  a  difference  of  pressure  between  blood  and  lu-ine  considerably  over  50  mm.  Hg. 
Under  such  circumstances  the  vu-eter  pressure  will  be  higher,  and  the  difference  of 
pressure  between  urine  and  blood  less,  the  more  rapid  the  formation  of  lu'ine 
by  the  glomeruli.  In  a  number  of  experiments  by  V.  E.  Henderson  it  was  found 
that  the  figure  B.P.  -  U.P.  tended  to  approximate  40  mm.  Hg  the  more  rapid 
the  secretion  of  urine  was.  With  a  slow  secretion  the  flow  of  urine  apparently 
ceased  when  there  was  as  much  as  80  mm.  Hg  difl'erence  of  pressiu-e  on  the 
two  sides  of  the  glomerular  membrane. 

We  may  conclude  that,  for  the  production  of  any  urine  by'  the 
kidney,  a  certain  minimum  difference  of  pressure  is  necessary  between 
the  blood  in  the  glomeruli  and  the  urine  in  the  tubule,  and  that  this 
difference  becomes  less  the  smaller  the  protein  content  of  the  blood. 
Since  the  only  work  required  in  the  formation  of  a  protein-free  filtrate 
from  the  blood  is  that  due  to  the  osmotic  pressure  of  the  proteins  them- 
selves, and  the  observed  difference  of  pressure  during  secretion  is 
greater  than  this  osmotic  pressure,  we  are  justified  in  concluding,  pro- 
visionally at  any  rate,  that  the  mechanical  factors  present  at  the  upper 
end  of  the  urinary  tubule  are  sufficient  to  account  for  the  production 
of  a  glomerular  transudate  free  from  protein,  but  containing  the  same 
proportion  of  water  and  salts  as  the  blood-plasma  circulating  through 
the  capillaries. 

If  the  process  occurring  in  the  glomeruli  is  simply  one  of  filtration, 
three  conditions  must  be  realised  : 

(1)  The  amount  of  filtrate,  so  long  as  the  ureter  pressure  is  con- 
stant, must  depend  on  the  pressure  and  rate  of  flow  of  the  blood  in 
the:  glomerular  capillaries,  and  must  fall  or  rise  with  the  latter. 

(2)  The  constitution  of  the  fully  formed  urine  as  it  appears  in  the 
ureters,  after  modification  by  addition  or  subtraction  on  the  part  of 


THE  SECRETION  OF  URINE  127:^ 

the  tubular  cells,  must  approximate  more  closely  to  the  supposed 
jjlomerular  transudate,  contaiuinf^  the  same  ))ro]>ortion  of  salts  as  the 
blood-plasma,  the  more  rapidly  the  formation  of  the  j^lonierular  transu- 
date takes  place :  i.e.  the  quicker  the  flow  of  urine  the  more  nearly 
must  its  composition,  reaction,  and  osmotic  pressure  resemble  those 
of  the  blood-serum. 

(3)  The  total  quantity  of  solids  excreted  in  any  given  time  must 
be  increased  with  any  increase  in  the  urinary  flow.  For,  whatever  the 
activity  of  the  tubules,  the  glomeruh  must  blindly  turn  out  a  certain 
proportion  of  solids  with  every  cubic  centimetre  of  fluid  that  they 
form. 

We  may  deal  first  with  the  influence  of  alterations  in  the  renal 
blood-supply  on  the  flow  of  urine.  Ligature  of  the  renal  vein  diminishes 
and  soon  stops  the  flow  altogether.  Since  this  procedure  must  cause 
a  large  rise  of  pressure  in  the  capillaries  of  the  kidney,  this  result  was 
regarded  by  Heidenhain  as  disproving  any  possibility  of  the  glomerular 
process  being  of  the  natm"e  of  a  filtration.  At  any  given  time,  how- 
ever, the  glomeruli  contain  but  little  blood.  With  total  cessation 
of  the  renewal  of  this  blood,  their  contents  will  rapidly  become  so 
concentrated  that  they  will  be  little  more  than  a  mass  of  red  cor- 
puscles. No  filtration  of  water  and  salts  can  take  place  unless  there  is 
a  continual  renew^al  of  the  fluid  on  the  blood  side  of  the  filter. 

On  the  other  hand,  alterations  in  the  blood-supply  to  the  kidney, 
determined  by  changes  on  the  arterial  side,  have  pronounced  effects 
on  the  amount  of  urine  formed.  The  pressure  in  the  glomerular 
capillaries  and  the  rate  of  flow  through  these  capillaries  can  be 
increased  in  either  of  two  ways  : 

(o)  By  increase  of  the  driving  force,  i.e.  the  general  blood  pressiu'e  ; 

(6)  By  a  diminution  of  the  resistance  to  the  flow  of  blood  through 
the  kidneys,  as  by  dilatation  of  the  vessels  of  this  organ. 

The  blood-flow^  through  the  kidney  can  be  investigated  either  by 
recording  the  total  volume  of  this  organ  or  by  determining  the  amount 
of  blood  which  leaves  it  through  the  renal  vein,  according  to  the 
methods  described  in  chapter  xiii. 

It  is  necessary  at  the  same  time  to  take  a  record  of  the  arterial 
blood  pressure  by  means  of  a  mercurial  manometer.  It  is  evident 
that  an  expansion  of  the  kidney  may  be  caused  by  a  rise  of  general 
arterial  pressure,  or,  the  latter  remaining  constant,  by  a  dilatation  of 
the  kidney- vessels  ;  and,  conversely,  a  fall  of  kidney  volume  may 
be  due  either  to  a  fall  of  general  blood  pressure  or  to  a  constriction 
of  the  renal  blood-vessels.  By  taking  these  two  records  it  is  possible 
to  tell  whether  a  given  increase  of  blood-flow  through  the  organ  is  of 
local  or  of  general  causation,  i.e.  is  active  or  passive.  Thus  the  volume 
f  the  kidney  gives  us  an  indirect  clue  to  the  pressure  in  and  the  flow 


1274 


PHYSIOLOGY 


through  the  kidney-vessels.  The  flow  through  the  vessels  can  be  deter- 
mined directly  either  by  a  cannula  in  the  inferior  vena  cava,  all  veins 
other  than  the  renal  being  clamped,  or  by  Brodie's  method  already 
described  (p.  1119). 

The  results  of  the  experiments  carried  out  by  these  methods  can 
be  represented  in  the  following  tabular  form  : 


Procedure 

General  blood 
pressure 

Renal  vessels 

Kidney  volume 

Urinary  flow 

Division     of      spinal 
cord  in  neck 

Falls  to 
40  mm. 

Relaxed 

Shrinks 

Ceases 

Stimulation  of  cord  . 

Rises 

Constricted 

Shrinks 

Diminished 

Stimulation    of    cord 
after     section     of 
renal  nerves 

Rises 

Passively 
dilated* 

Swells 

Increased 

Stimulation  of  renal 

Unaffected 

Constricted 

Slirinks 

Diminished 

nerves 

Stimulation  of 
splanchnic  nerve 

Rises 

Constricted 

Shrinks 

Diminished 

Division  of  one 
splanchic  nerve  : 

(a)  In  dog 

[b)  In  rabbit      . 

Unaffected 

Falls 

Dilated 
Relaxed 

Swells  (?) 
Shrinks  (?) 

Increased 
Diminished 

Plethora 

Rises 

Dilated 

Swells 

Increased 

H?emorrhage    . 

Falls 

Constricted 

Shrinks 

Diminished 

It  will  be  seen  that  in  every  case  where  an  increased  blood-flow, 
attended  with  a  rise  of  blood  pressure  in  the  glomerular  capillaries,  is 
brought  about,  the  urinary  flow  is  at  the  same  time  increased. 

Another  factor,  altering  the  ease  with  which  filtration  of  watery 
fluid  and  salts  would  take  place  through  the  glomerular  capillaries, 
would  be  the  composition  of  the  blood-plasma.  Any  dilution  of  this 
plasma  must  render  filtration  more  easy,  while  a  concentration  would 
make  it  more  difiicult.  As  a  matter  of  fact  hydrsemia,  and  especially 
hydrsemic  plethora  caused  by  injection  of  normal  saline  into  the  circu- 
lation, evoke  an  increased  flow  of  urine.  A  smaller  effect  is  produced 
by  injection  of  defibrinated  blood,  and  if  the  blood  has  been  previously 
concentrated  by  depriving  the  animals  of  water,  there  may  be  little  or 
no  increase  in  flow,  in  consequence  of  the  high  osmotic  pressure  of  the 
proteins  of  the  plasma  injected. 

Experiments  on  the  action  of  diuretics  have  a  close  bearing  on  the 
nature  of  the  process  occurring  in  the  glomeruli.  A  large  increase  in 
the  urinary  flow  can  be  brought  about  by  the  intravenous  injection 
of  saline  diuretics  such  as  sodium  sulphate  or  potassium  nitrate,  or  of 


THE  SECRETION  OF  URINE  1275 

neutral  crystalloids  such  as  urea  or  sugar.  The  question  arises  whether 
the  chemical  changes  thereby  induced  in  the  renal  circulation  are 
sufficient  to  account  for  the  diuresis.  Three  factors  might  be  concerned 
in  promoting  an  increased  glomerular  transudation.  These  are  : 

(1)  A  rise  of  pressure  in  the  j^lomerular  capillaries. 

(2)  Acceleration  of  the  blood-flow  from  the  capillaries. 

(3)  Diminution  of  the  amount  of  proteins  in  the  blood-plasma. 
When  a  concentrated  solution  of  salt  is  injected  into  the  circulation 

the  osmotic  pressure  of  the  plasma  is  raised  and  water  passes  from  the 
tissue-cells  into  the  blood-stream,  in  consequence  of  the  osmotic 
differences  between  the  blood  and  cells  so  induced.  As  a  result  the 
total  volume  of  the  circulating  fluid  is  increased  by  the  addition  to  it 
of  water  derived  from  the  tissues,  i.e.  a  condition  of  hydraemic  plethora 
is  set  up  just  as  if  a  large  bulk  of  normal  saline  fluid  had  been  injected 
into  the  circulation.  So  long  as  this  hydra^mic  plethora  continues,  so 
long  is  there  a  rise  both  in  arterial  and  venous  pressures  and  an  increase 
in  the  velocity  of  the  circulating  blood.  The  kidney  placed  in  an  onco- 
meter shows  a  gTeat  increase  in  volume.  While  the  plethora  lasts 
there  are  mechanical  conditions  at  work  in  the  kidneys,  i.e.  in- 
creased pressure,  increased  rate  of  flow,  and  diminished  concentration 
of  plasma — all  of  which  would  concur  in  producing  an  increased 
glomerular  transudation.  With  certain  salts,  such  as  sodium  chloride, 
the  diuresis  is  coterminous  with  the  hydra?mic  plethora,  but  with 
other  members  of  .this  class,  such  as  grape  sugar,  the  diuresis  outlasts 
the  plethora,  so  that  the  continued  increased  secretion  of  urine  leads 
to  an  actual  concentration  and  diminution  of  the  volume  of  the  circu- 
lating blood,  as  is  shown  in  Fig.  531.  If  the  kidney  be  placed  in  an 
oncometer,  it  is  found  that  the  dilatation  of  the  kidney  outlasts  the 
plethora,  and  comes  to  an  end  only  with  the  cessation  of  the  increased 
urinary  flow.  There  must  be  local  influences  at  work  (perhaps  the 
direct  effect  of  the  sugar  on  the  blood-vessels)  which  lead  to  an 
active  dilatation  of  the  renal  vessels,  and  a  consequent  rise  of 
pressure  and  velocity  of  the  blood  in  the  glomeruli.  That  the 
vascular  change  is  really  responsible  for  the  increased  urinary  flow 
is  shown  by  the  fact,  determined  by  Cushny.  that  if  the  swelling  of 
the  kidney  be  prevented  by  means  of  an  adjustable  clamp  on  the  renal 
artery,  no  diuresis  is  produced  ;  so  long  as  the  kidney  is  kei)t  at  its 
normal  size  the  flow  of  urine  remains  at  the  same  rate  as  before. 

With  regard  to  the  specific  diuretics,  such  as  caffeine,  the  question 
is  not  quite  so  clear.  In  most  cases  injection  of  cafloine  in  the  rabbit 
brings  about  a  dilatation  of  the  kidney  and  a  proportional  increase  in 
the  secretion  of  urine.  But  cases  have  been  recorded  in  which  ex- 
pansion of  the  kidney  occurred  without  any  increase  in  urinary  flow, 
and,  on  the  other  hand,  augmented  urinary  flow  without  any  increase  in 


1276 


PHYSIOLOGY 


the  kidney-volume,  or  even  in  the  rate  of  blood-flow  through  the 
kidney  (as  determined  by  Brodie's  method).  The  general  rule,  how- 
ever, is  that  a  greater  rate  of  blood-flow  is  obtained  fari  passu  with 
the  increased  urinary  flow  ;  and  a  consideration  of  certain  peculiarities 


ao     'ju     luu    110    rju    150    140     io& 


Fig.  531.  A  comparison  of  the  effects  of  intravenous  injection  of  30  grm. 
glucose  in  concentrated  solution  on  the  arterial  blood  pressure,  the  con- 
centration of  the  blood,  the  kidney  volume,  and  the  urinary  flow. 
Abscissa  =  time  in  minutes. 


in  the  renal  circulation  must  prevent  us  from  laying  too  much  stress 
on  apparent  exceptions  to  the  rule.  To  the  blood  entering  the  kidneys 
by  the  renal  arteries  two  ways  are  open.  The  blood  may  pass  through 
the  vasa  aiferentia,  through  the  glomeruli  and  tubular  capillaries,  back 
to  the  renal  vein.  On  the  other  hand,  it  may  escape  the  glomeruli 
altogether,  and  pass  through  the  vasa  recta  directly  into  the  inter- 
lobular capillaries  and  so  into  the  renal  veins.  It  is  a  common  experience, 
in  injecting  the  blood-vessels  of  the  kidneys  post-mortem,  to  find  the 


THE  SECRETION  OF  URINE 


1277 


renal  arteries,  interlobular  capillaries,  and  veins  filled  to  distension 
with  the  injected  mass,  but  hardly  any  in  the  glomeruli.  One'must 
assume  in  such  a  case  that  there  has  been  spasmodic  contraction  of  the 
muscular  coats  of  the  vasa  afferentia  [cp.  Fig.  532).  The  normal  amount 
of  blood  might  therefore  circulate  through  the  kidney  without  any 
flowing  through  the  filtering  apparatus,  i.e.  the  glomeruli.  On  the  other 
hand,  a  dilatation  of  the  afferent  vessels  and  a  slight  constriction  of  the 
efferent  vessels  would  cause  a  considerable  rise  of  pressure  in  the 
glomerular  capillaries,  and  a  consequent  increased  transudation,  without 
necessarily  altering  to  any  marked  extent  the  total  circulation  of  blood 
through  the  whole  organ.  The  changes  in  the  afferent  and  efferent 
vessels  and  the  glomeruli  are,  however,  beyond  our  control  or  powers 


Fig.  532.  Diagram  (after  Mokat)  to  illustrate  the  effect  of  active  changes 
in  the  vasa  afferentia  and  efferentia  on  the  pressure  in  the  glomerular 
capillaries.  If  the  vas  affeiens  concrtricts,  the  pressure  will  be  repre- 
sented by  the  lower  dotted  line.  On  the  other  hand,  constriction  of 
the  vas  efferens  would  raise  the  pressure  in  the  glomerulus  till  it  almost 
equalled  that  in  the  renal  artery,  as  is  shown  by  the  upper  dotted  line. 
A,  arteries  ;   G,  glomenilar  capillaries  ;   c,  tubular  capillaries  ;   v,  vein. 


of  observation,  so  that  it  is  impossible  to  devise  at  the  present  time 
any  crucial  experiment  which  might  decide  the  nature  of  the  process 
occurring  in  the  glomeruli. 

THE  COMPOSITION  OF  THE  URINE.  If  the  glomerular  func- 
tion is  that  of  mere  filtration,  we  should  expect  that  the  more  rapidly 
the  process  occurs,  the  more  nearly  would  the  urine  which  is  turned 
out  into  the  ureters  resemble  the  blood-plasma  in  composition,  reac- 
tion, and  osmotic  pressure,  since  the  glomerular  filtrate  hurried  through 
the  tubules  would  have  very  little  time  to  undergo  any  changes  result- 
ing in  its  concentration.  If,  on  the  other  hand,  the  diuresis,  produced  by 
salt  or  sugar  solutions,  is  to  be  ascribed  to  a  stimulation  of  the  renal 
epithelium,  the  differences  between  blood-plasma  and  urine  should  be 
greatest  at  the  height  of  the  diuresis,  when  the  concentration  of  the 
specific  stimulant  is  also  at  its  highest.  The  following  experiment  shows 
that  the  more  rapid  the  secretion  of  urine,  the  more  closely  does  its 


1278  PHYSIOLOGY 

concentration,  as  indicated  by  its  osmotic  pressure  and  depression  of 
freezing-point  (A),  approximate  that  of  the  blood-plasma. 

A  dog  received  40  Rrm.  of  dextrose  dissolved  in  40  cm.  of  water. 
The  following  Table  represents  the  relative  concentrations  of  urine 
and  blood-serum  at  different  stages  in  the  diuresis  thereby  produced  : 


Time 


11.30-12 


Urine 


10  c.c. 


Rate  of  liow 


3-3 


A  of  urine 


2-360 


A  of  blood-serum 


0-625  (at  12.0) 


From  12.0  to  12.7  injected  40  grm.  dextrose  into  jugular  vein 


12.7  -12.15 
12.16-12.20 
12.20-12.30 
12.30-12.40 

12.40-12.50 


35  c.c. 
20  c.c. 
52  c.c. 
45  c.c. 

.22  c.c. 


45 

50 
52 
45 


1-210 
0-975 
0-835 

0-825 

0-830 


0-700  (at  12.16) 

0-700  (at  12.30) 
0-675 (at  12.40) 
0-675  (at  12.50) 


A  still  closer  approximation  of  the  concentration  of  the  urine  to 
that  of  the  plasma  was  obtained  by  Galeotti  in  some  experiments 
in  which  the  modifying  influence  of  the  tubular  epithelium  on  the 
glomerular  transudate  had  been  prevented  by  poisoning  the  animal 
with  corrosive  sublimate,  which  causes  destruction  of  the  epithelium, 
but  is  said  to  leave  the  glomeruli  intact. 

Since  the  glomerular  transudate  must  have  a  concentration 
approximately  identical  with  that  of  the  blood-plasma,  it  would  be 
impossible  for  a  urine  formed  by  mere  filtration  to  have  a  concentration 
less  than  that  of  the  blood-plasma.  It  is,  however,  of  frequent  occur- 
rence that,  after  copious  potations  of  tea  or  light  beer,  urine  is  passed 
with  an  osmotic  pressure  and  a  molecular  concentration  considerably 
below  that  of  the  blood.  In  one  case  Dreser  obtained  a  urine  with 
a  freezing-point  of  A  =  0*16°  C,  and  the  same  result  has  been 
obtained  on  one  or  two  occasions  when  the  diuresis  has  been  produced 
by  the  administration  of  caffeine.  If  we  assume  that  this  hypotonic 
fluid  is  formed  by  the  glomeruli,  we  must  at  once  give  up  any  idea 
of  the  process  in  these  structures  being  essentially  one  of  filtration. 
But  there  is  evidence  that  the  epithelium  of  the  tubules  can  secrete 
water  as  well  as  solid  constituents.  The  fine  adaptation  of  the  kidney 
to  slight  changes  in  the  composition  of  the  blood  is  apparently  an 
endowment  of  the  tubular  epithelium,  and  in  those  cases  where  large 
quantities  of  hypotonic  urine  are  passed  there  is  not  at  any  time  any 
appreciable  change  either  in  the  composition  of  the  blood  or  in  its 
total  volume.  Water  is  absorbed  from  the  alimentary  canal  and  is 
almost  immediately  excreted  by  the  kidneys.  When  we  attempt  to 
produce  the  same  effect  by  infusion  of  large  quantities  of  water  or 
hypotonic  solutions  into  the  blood-stream,  we  get  a  flow  of  urine 


THE  SECRETION  OF  URINE  1279 

apparently  determined  entirely  by  the  circulation  through  the  kidney 
and  having  a  concentration  not  inferior  to  that  of  the  blood.  The 
passage  of  hypotonic  urine  can  be  ascribed  to  a  modification  of  the 
glomerular  transudate  as  it  passes  through  the  tubules,  a  modifica- 
tion due  partly  to  the  absorption  of  salts  from  the  fluid,  partly,  perhaps 
chiefly,  to  a  secretion  of  water  or  extremely  dilute  salt  solution  by  the 
cells  of  the  tubules  themselves. 

Certain  other  observations  accord  with  our  hypothesis  that  in  Bowman's 
capsule  a  fluid  is  transuded  having  the  same  molecular  concentration  as  blood- 
plasma,  and  therefore  considerably  less  concentrated  than  normal  urine. 
Ribbert  succeeded  in  extirpating  the  whole  of  the  medullary  portion  of  the  kidney 
in  the  rabbit,  leaving  the  cortex  intact,  and  found  in  this  case  that  during  the 
survival  of  the  animal  the  urine  passed  was  much  more  dilute  than  normal. 
In  cases  where  there  is  destruction  of  the  tubular  epithelium,  while  the  glomeruli 
remain  intact,  either  in  consequence  of  disease  or,  as  in  Galeotti's  experiments, 
as  a  result  of  poisons,  we  are  accustomed  to  obtain  a  dilute  copious  lu-ine  ;  and 
the  continual  passage  of  such  urine  is  in  man  regarded  as  a  sign  of  one  form  of 
renal  disease. 

The  experimental  facts  which  we  have  passed  in  review  do  not 
therefore  negative  the  view  that  the  glomerular  epithelium  plays  the 
part  of  a  passive  filter  in  the  formation  of  urine,  and  that  the  energy 
of  the  process  by  which  '  m-ine  '  is  produced  in  Bowman's  capsule  is 
entirely  furnished  by  the  heart  in  driving  the  blood  at  a  high  pressure 
through  the  glomerular  capillaries. 

FUNCTIONS  OF  THE  RENAL  TUBULES 
Whatever  the  natm'e  of  the  glomerular  activity,  it  is  evident  that 
the  multiform  epithehum  of  the  tubules  may  alter  the  glomerular 
transudate,  either  by  the  absorption  or  by  the  secretion  of  water  or 
sohd  constituents.  We  may  deal  with  the  evidence  for  the  occurrence 
of  these  two  processes  separately. 

SECRETION  BY  THE  URINARY  TUBULES.  Although  it  is 
impossible  to  collect  the  secretion  of  the  glomeruli  apart  from 
that  of  the  tubules,  the  arrangement  of  the  blood-vessels  in  cer- 
tain animals  enables  us  to  influence  separately  the  circulation  to 
these  two  parts  of  the  kidney.  The  amphibian  kidney  receives  a 
blood-supply  from  two  sources.  A  number  of  renal  arteries  leaving 
the  aorta  enter  the  kidney  and  supply  the  whole  of  the  glomeruli, 
the  vasa  efferentia  from  which  pass,  as  in  the  mammalian  kidney,  into 
the  intertubular  capillaries.  These  are  also  supplied  with  blood  of 
venous  character  by  the  renal  portal  vein.  If  all  the  renal  arteries  be 
divided  or  ligatured,  the  glomeruli,  as  was  shown  by  Nussbaum,  are 
entirely  cut  out  of  the  circulation,  though  the  tubules  continue  to 
receive  venous  blood  through  the  renal  portal  vein.  Nussbaum 
stated  that  ligature   of  all  the   renal  arteries  caused  cessation  of 


1280  PHYSIOLOOY 

the  urinary  secretion,  which  could  be  reinduced  by  injection  of 
urea.  He  conckided  that  urea  with  water  was  secreted  by  the 
tubules,  whereas  peptone,  sugar,  and  haemoglobin  were  turned  out 
by  the  glomeruli.  Beddard  showed  that  these  results  of  Nussbaum's 
must  have  been  due  to  the  fact  that  he  had  not  obstructed  the 
whole  of  the  renal  arteries.  One  or  two  of  these  small  vessels  will 
suffice  to  supply  blood  to  a  considerable  number  of  the  glomeruli. 
After  complete  obstruction  of  the  arteries,  no  urinary  flow  could 
be  induced  even  with  subcutaneous  injection  of  urea.  But  the 
cutting  off  of  the  arterial  blood-supply  from  the  tubules  caused  a 
rapid  destruction  of  the  tubular  epithelium,  so  that  the  result  of  the 


-Aorha 


Vena  cava 

; Renal  arl-eries 


Tesl- 

kidn 
Renal  pocl-al 

Anr.  abdom.v. 


I- — Femoral  v. 

Fjii.J533.     The  vascular  sxijjply  to  the  kidney  in  the  frog. 

experiment  could  not  be  taken  as  negativing  the  possibility  of  this 
epithehum  having,  when  in  a  normal  state  of  nutrition,  some  secretory 
power.  He  therefore  carried  out,  with  Bainbridge,  another  series  of 
experiments  of  the  same  description,  in  which  the  frogs,  after  ligature 
of  the  renal  arteries,  were  kept  in  an  atmosphere  of  pure  oxygen. 
Under  these  circumstances  sufficient  oxygen  diffused  into  the  blood 
of  the  renal  })ortal  vein  to  maintain  an  adequate  supply  of  this  gas  to 
the  tubules.  No  desquamation  of  the  epithehum  resulted,  and  in- 
jection of  urea  produced  a  small  flow  of  urine  even  when,  by  subsequent 
injection  of  the  blood-vessels,  it  was  proved  that  every  glomerulus  had 
been  cut  out  of  the  circulation.  Similar  results  have  been  obtained 
by  Brodie  and  Cullis  in  certain  experiments  in  which  oxygenated 
Ringer's  fluid  was  led  by  the  renal  portal  vein  through  the  surviving 
kidney  of  the  frog.  A  small  flow  of  urine  was  obtained,  especially 
after  urea  or  potassium  nitrate  had  been  added  to  the  fluid.  The 
quantities  of  urine  obtained  in  these  experiments  were  too  small  to 
admit  of  a  proper  analysis  or  of  a  comparison  of  their  molecular 
concentration  with  that  of  the  blood-serum  of  the  animal. 


THE  SECRETION  OF  URINE  1281 

The  view  that  a  portion  of  the  tubules  is  secretory  in  function 
is  further  supported  by  histological  examination  of  these  structures 
under  various  conditions  of  activity.  In  the  cells  of  the  convoluted 
tubules  various  kinds  of  granules  and  of  vacuoles  may  be  distinguished. 
Gurwitsch  divides  these  vacuoles  into  three  classes  : 

(1)  Large  granules  staining  densely  with  osmic  acid,  and  probably 
rich  in  lecithin. 

(2)  Smaller  very  numerous  granules  consisting  of  some  form  of 
protein  material. 

(3)  Large  vacuoles  lying  close  to  the  free  margin  of  the  cells,  whose 
contents  do  not  undergo  coagulation  with,  the  ordinary  fixing  reagents, 
and  therefore  are  free  from  protein,  fat,  or  mucin.  These  vacuoles  are 
especially  marked  in  kidneys  which  are  secreting  at  a  great  rate,  in 
consequence  of  the  injection  of  saline  diuretics  or  of  large  quantities 
of  normal  salt  solution.  They  may  be  regarded  as  excretory  vacuoles 
and  consist  of  water  or  saline  fluids  which  have  been  collected  by  the 
cells  and  are  being  passed  on  by  them  to  the  lumen  of  the  tubules. 

As  a  rule  it  is  impossible  to  trace  any  definite  constituent  of  the 
urine  on  its  way  through  the  cells  of  the  tubules.  But  if  a  solution  of 
uric  acid  in  piperazin  be  injected  intravenously  into  a  rabbit,  the 
kidneys,  taken  twenty  to  sixty  minutes  after  the  injection,  present 
tubules  full  of  uric  acid  concretions.  In  the  medullary  portion  of  the 
kidney  this  uric  acid  precipitate  is  confined  to  the  lumen  of  the  tubules, 
but  in  the  convoluted  tubules  granules  of  uric  acid  are  to  be  found  in 
the  epithelial  cells,  especially  towards  their  inner  border.  Since  these 
cells  are  able  to  excrete  uric  acid  when  present  in  abnormal  quantities  in 
the  blood,  it  is  a  reasonable  assumption  that  they  also  undertake  the 
secretion  of  this  substance  under  normal  conditions.  Certain  observers 
have  in  fact  described  the  presence  of  lurate  granules  in  the  cells  of  the 
convoluted  tubules  of  the  bird's  kidney. 

Although  the  larger  number  of  the  urinary  constituents  must 
escape  detection  on  their  way  through  the  cells,  we  can  throw  some 
light  on  the  excretory  functions  of  the  kidney  by  studying  the 
mechanism  by  means  of  which  it  excretes  certain  dyestuffs,  such  as 
sulphindigotate  of  soda  ('  indigo  carmine ').  If  the  indigo  be  injected  into 
the  veins,  it  is  excreted  in  a  concentrated  form,  both  by  the  liver  and 
by  the  kidney,  so  that  the  urine  assumes  a  dark  blue  colom-.  If  the 
animal  be  killed  when  the  excretion  of  the  pigment  is  at  its  height, 
and  the  kidneys  be  rapidly  fixed  with  absolute  alcohol  (which  precipi- 
tates the  dyestuff),  all  parts  of  the  kidney  present  a  blue  colour,  which 
is  especially  marked  in  the  medulla.  Under  these  circumstances  the 
urine,  which  is  being  excreted  by  the  glomeruli,  rapidly  carries  down 
the  dyestufi,  wherever  it  may  be  turned  out,  into  the  tubules  of  the 
pyramids.  In  order  to  discover  the  exact  locality  of  the  cells  involved 

81 


1282  PHYSIOLOGY 

in  its  excretion,  we  must  stop  the  glomerular  transudate  by  some 
means  or  other.  This  stoppage  of  the  urinary  flow  can  be  effected  in 
two  ways,  viz.  by  section  of  the  spinal  cord  in  the  neck,  so  as  to 
reduce  the  blood  pressure  to  about  40  mm.  Hg,  i.e.  below  the  minimum 
necessary  for  the  production  of  urine,  or  by  cauterising  portions  of 
the  surface  of  the  kidney  by  means  of  silver  nitrate.  If  the 
indigo  be  injected  into  the  veins,  after  section  of  the  cord,  and 
the  animal  be  killed  half  an  hour  later,  and  the  kidneys  fixed 
with  absolute  alcohol,  they  are  found  to  be  of  a  bright  blue 
colour,  although  no  urine  has  been  secreted.  On  cutting  into  the 
kidneys  the  colour  is  seen  to  be  confined  to  the  cortex,  and  on  making 
microscopic  sections  granules  of  the  pigment  are  found  within  the 
lumen  and  in  the  epithelial  cells  of  the  convoluted  tubules.  If  the 
kidneys  have  been  cauterised,  the  stain  is  confined  to  the  convoluted 
tubules  of  the  cortex  only  under  those  areas  which  have  been  cauterised, 
and  where  the  glomerular  functions  have  been  abolished.  It  has  been 
suggested  that  the  appearances  after  the  injection  of  indigo  are  due, 
not  to  the  secretion,  but  to  the  absorption  of  water  in  the  convoluted 
tubules.  A  certain  amount  of  the  dyestuff  is  thus  rendered  visible 
by  becoming  more  concentrated,  and  is  precipitated  in  a  granular  form, 
as  soon  as  the  salt  concentration  of  the  fluid  reaches  a  certain  height. 
The  fact  that  these  appearances  are  wanting  after  the  injection  of 
ordinary  carmine,  which  stains  the  glomeruli  as  well  as  the  tubules, 
combined  with  the  histological  facts  mentioned  in  the  last  para- 
graph, render  this  a  somewhat  forced  explanation  ;  and  we  must  take 
the  results  of  the  injection  of  indigo-carmine  as  telling  rather  in  favour 
of  a  secretory  than  of  an  absorptive  function  on  the  part  of  the  con- 
voluted tubules. 

The  question  as  to  the  secretory  activity  of  the  kidney  can  be 
attacked  from  another  side.  The  glomerular  filtrate  can  contain  only 
those  crystalloids  of  the  blood  which  are  diffusible  and  are  not  closely 
combined  with  its  colloidal  constituents.  Lowi  has  shown  that  in  this 
connection  a  contrast  is  to  be  drawn  between  the  behaviour  of  sub- 
stances, such  as  urea  or  sodium  chloride,  and  certain  other  constituents 
of  the  blood  such  as  phosphates  or  sugar.  Any  increase  in  the  rate  at 
which  the  glomerular  secretion  takes  place  must  cause  a  corresponding 
increase  in  the  total  amount  of  the  sohd  diffusible  constituents  of  the 
blood-plasma  which  are  turned  out  within  a  given  time.  Thus  every 
diuresis  increases  the  total  output  of  chlorides  and  of  m'ea.  On  the 
other  hand,  a  diuresis  caused,  for  example,  by  drinking  large  quantities 
of  water  does  not  increase  the  total  output  of  phosphates  in  a  given 
time,  nor  does  it  increase  the  very  small  amount  of  sugar  which  is 
normally  excreted  by  the  kidneys.  If,  however,  sodium  phosphate  be 
previously  injected  into  the  blood,  then  any  diuresis  increases  the 


THE  SECRETION  OF  URINE  1283 

output  of  this  salt.  The  same  thing  holds  for  sugar.  If  an  excess  of 
free  uncombinecl  sugar  be  present  in  the  blood,  either  in  consequence 
of  intravenous  injection  of  this  substance  or  as  a  result  of  previous 
extirpation  of  the  pancreas,  any  form  of  diuresis  will  increase  the  rate 
at  which  it  is  turned  out  by  the  kidneys.  Lowi  concludes  that  phos- 
phates, which  must  be  present  in  minimal  quantities  in  the  glomerular 
transudate,  are  for  the  most  part  secreted  by  the  activity  of  the  cells 
of  the  convoluted  tubules.  Under  abnormal  conditions,  e.g.  as  after 
administration  of  phloridzin,  the  cells  of  the  kidneys  can  be  excited  to 
a  similar  activity  with  regard  to  sugar.  After  phloridzin  injection  the 
urine  contains  considerable  quantities  of  sugar,  but  the  rate  at  which 
the  sugar  is  secreted  is  not  affected  in  any  way  by  raising  the  rate  of 
urinary  secretion,  e.g.  by  the  injection  of  such  substances  as  sodium 
sulphate,  which  increases  the  rapidity  of  the  glomerular  process  of 
transudation. 

ABSORPTION  BY  THE  RENAL  TUBULES.  The  experiments 
of  Ribbert,  mentioned  above,  in  which  removal  of  the  medullary 
portion  of  the  kidney  led  to  the  formation  of  an  increased  quan- 
tity of  a  more  watery  urine,  points  to  the  possession  by  the 
tubules  of  a  power  of  absorbing  water.  We  have  other  evidence 
that  this  power  of  resorption  is  not  confined  to  water,  but  may  affect 
also  the  dissolved  constituents  of  the  glomerular  transudate.  '  It  was 
pointed  out  by  Meyer  that,  if  two  salts,  such  as  sodium  sulphate  and 
sodium  chloride,  were  present  at  the  same  time  in  the  glomerular 
transudate,  any  process  of  resorption  should  affect  chiefly  the  more 
diffusible  salt,  namely,  sodium  chloride.  Such  a  differential  resorption 
would  account  for  the  much  greater  diuretic  power  of  sodium  sulphate 
ai  compared  with  sodium  chloride.  In  certain  experiments  Cushny 
produced  a  diuresis  by  the  injection  of  equal  parts  of  equivalent 
NaCl  and  Na2S04  solutions  into  the  veins  of  a  rabbit.  An  increased  flow 
of  urine  was  produced  which  lasted  two  hoiu:s  and  a  half.  The  chlorides 
of  the  urine  rose  with  the  diuresis  and  reached  their  maximum  at  the 
height  of  the  urinary  flow.  They  then  sank,  and  in  some  experiments 
had  practically  disappeared  from  the  urine  towards  the  end  of  the 
observation.  The  concentration  of  the  sulphates,  however,  continued 
to  rise  in  the  urine  to  the  end  of  the  experiment.  Thus  in  the  first  of 
two  identical  experiments,  when  the  rabbit  was  killed  at  the  height 
of  the  diuresis,  the  serum  contained  0-547  per  cent,  chlorine  and  0-259 
per  cent,  sulphate,  while  the  urine  contained  0-372  per  tent,  chlorine 
and  0-546  per  cent,  sulphate.  In  the  second,  in  which  the  rabbit  was 
killed  when  the  rate  of  the  urinary  flow  had  considerably  diminished, 
the  serum  contained  0-493  per  cent,  chlorine  and  0-191  per  cent, 
sulphate,  wliile  the  urine  contained  -094  [)er  cent,  chlorine  and  2-0 
per  cent,  sulphate.     These  results  are  illustrated  in  Fig.  534. 


1284  PHYSIOLOGY 

The  difference  between  the  two  salts  can  be  made  still  more 
striking  if  the  process  of  resorption  be  augmented  by  increasing  the 
pressure  within  the  tubules  by  partial  obstruction  of  one  ureter. 
Thus  in  one  experiment,  where  diuresis  was  produced  by  the  injection 
of  30  c.c.  of  a  solution  containing  5-85  per  cent.  Nad  +  14-2  per  cent. 
Na2S04,  the  right  ureter  was  partially  clamped  so  as  to  make  the 


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ij 

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.-_ 

_.. 

-J 

"■^ 

15  30  45  60  75  ^0  105  120  155 

Fig.  534.     Curves  showing  excretion  of  lu-ine  (thick  line),  of  sulphate  mole- 
cules     (-i^,  thin  line),  and  of  CI  molecules  (^^t-^,  dotted  line),  after 

injection  of  50  c.c.  of  a  solution  containing  1-775  grm.  CI  and  4-8  grm 
SO4  i»r  100  c.c.  The  black  line  along  the  ba.se  marks  the  duration 
of  the  injection.     (Cushny.) 


right  kidney  secrete  against  a  pressure  of  .'30  mm.  Hg.     The  following 
results  were  obtained  : 


Urine  c.c.            CI.  t-'. 

SO-1  g. 

4.37  till  4.47 

1  Left  kidney 
1  Riglit  kidney 
Diflferencc  (absorption) 

24            0-0809 
8           0-0142 

10     '    oor,77 

0-1080 
0-06G7 
0-041  ;i 

We  must  conclude  that  the  tubular  epithelium  possesses  the 
power  of  modifying  the  glomerular  transudate  not  only  by  the  absorp- 
tion of  water  but  also  by  the  absorption  of  dissolved  constituents, 
and  that  the  relative  permeability  of  the  cells  to  the  constituents 


THE  SEORRTTON  OF  URINE  12m 

is  at  any  rate  one  factor  in  determining  the  substances  absorbed.  It 
is  not,  however,  the  only  factor.  The  function  of  the  kidney  is  to 
preserve  the  normal  constitution  of  the  body  fluids  by  turning  out 
those  substances  which  are  abnormal  or  present  in  too  great  an  amount. 
The  behaviour  of  the  tubule  cells  with  regard  to  any  given  substance 
will  therefore  depend  to  a  certain  extent  on  the  previous  nutritive 
history  of  the  body. 

If,  for  instance,  in  consequence  of  the  administration  of  sodium 
chloride  in  large  quantities  to  the  animal  during  the  few  da\'s  preceding 
the  experiment,  the  body  is  overloaded  with  this  salt,  it  becomes  an 
abnormal  constituent  and  the  kidney  secretes  a  urine  far  richer  in 
sodium  chloride  than  is  the  blood-plasma.  Moreover,  when  diuresis 
is  produced  in  such  an  animal  by  the  injection  of  equivalent  quantities 
of  sodium  chloride  and  sodium  sulphate,  there  is  no  diminution  of 
the  NaCl  in  the  urine  towards  the  end  of  the  diuresis,  but  its  per- 
centage rises  steadily  as  the  rate  of  urinary  flow  diminishes.  On  the 
other  hand,  a  total  deprivation  of  sodium  chloride  extending  over 
several  days,  although  not  altering  to  any  large  extent  the  percentage 
amount  of  this  salt  in  the  blood-plasma,  leads  to  a  total  disappearance 
of  the  salt  from  the  urine,  the  whole  of  the  sodiunr  chloride  present 
in  the  glomerular  transudate  being  absorbed  on  its  way  through  the 
urinary  tubules. 

It  has  been  suggested  that  the  effects  of  certain  diuretics  on  the 
kidney,  such  as  caffeine,  diuretine,  or  theocine,  may  be  largely  condi- 
tioned not  so  much  by  their  influence  on  the  glomerular  circulation  as 
by  a  paralytic  effect  on  the  absorptive  functions  of  the  tubules. 
According  to  Lowi,  on  injection  of  caffeine  or  diuretine,  the  increase 
of  total  amount  of  urine  is  not  accompanied  by  any  diminution  in  the 
percentage  amount  of  ISTaCl.  Perhaps,  however,  the  strongest  evidence 
in  this  direction  is  afforded  by  an  experiment  of  Pototzky.  A  rabbit 
had  been  fed  on  a  diet  almost  totally  devoid  of  chlorides,  and  was 
therefore  excreting  a  m'ine  containing  only  -08  per  cent.  NaCl. 
Under  the  influence  of  diuretine  the  urine  was  increased  and  the  con- 
centration of  the  NaCl  rose  to  0-64  per  cent.  The  same  increase  in  the 
percentage  amount  of  sodium  chloride  in  the  urine  has  also  been 
observed  after  the  injection  of  theocine,  which  has  therefore  been 
specially  reconmiended  as  a  diuretic  in  cases  of  dropsy,  where  a 
diminution  of  the  salt  content  of  the  body  is  a  valuable  means  for  the 
diminution  of  the  dropsical  fluid  present  in  the  tissue  spaces. 

THE   RENAL  MECHANISM 
What  conclusions  can  we  cUaw  from  this  mass  of  experimental 
data  as  to  the  functions  of  the  kidney  as  a  whole,  and  as  to  the  part 
played  by  its  various  constituent  elements  in  the  secretion  of  urine  ? 


Ii>86  PHYRTOLOGY 

The  amazing  adaptability  of  its  functions  to  the  needs  of  the  organism 
has  been  abundantly  illustrated  in  the  facts  with  which  we  have 
dealt.  Its  ordinary  activity  is  determined  by  the  production,  as  a 
result  of  the  normal  processes  of  metabolism,  of  soluble  non-volatile 
substances  in  every  cell  of  the  body.  These  substances,  together 
with  the  excess  of  water  taken  in  with  the  food  above  that  lost  by 
respiration  and  cutaneous  transpiration,  are  turned  out  by  the  kidney 
as  urine.  The  activity  of  this  organ  must  therefore  be  determined 
in  the  first  place  by  chemical  stimuli.  It  must  react  to  the  slightest 
deviation  from  normal  of  the  blood  composition  by  excreting 
water  or  dissolved  substances.  This  delicate  sensibility  is  displayed 
in  two  directions : 

(1)  Under  the  influence  of  certain  substances,  such  as  urea,  uric 
acid,  or  water,  the  cells  of  the  convoluted  tubules  take  up  the  substance, 
which  is  in  excess,  from  the  surrounding  lymph  and  accumulate  it  in 
vacuoles,  which  are  discharged  on  the  inner  surface  of  the  cells  into 
the  lumen  of  the  tubules. 

(2)  Besides  this  specific  secretory  activity  of  the  cells  of  the  con- 
voluted tubules,  the  tubules  as  a  whole  are  endowed  with  the  power  of 
absorbing  both  water  and  dissolved  substances  from  the  fluid  in  their 
lumen.  Whether  this  absorptive  power  is  limited  to  the  cells  of 
Henle's  loop,  as  was  first  suggested  by  Ludwig,  or  occurs  coincidently 
with  secretion  in  the  cells  of  the  convoluted  tubules,  as  might  be 
imagined  from  the  close  analogy  between  the  structure  of  these  cells 
and  that  of  the  intestinal  epithelium,  we  have  not  sufficient  evidence 
to  decide.  We  do  know,  however,  that  the  quality  of  the  absorption 
is  strictly  regulated  according  to  the  needs  of  the  organism,  so  that 
the  constituents  which  are  precious  are  reabsorbed  for  service  in  the 
body,  while  those  which  are  in  excess  or  are  of  no  value  to  the  organism 
are  allowed  to  pass  out  into  the  ureters.  The  process  of  resorption 
is  indeed,  as  is  shown  by  Cushny's  experiments,  largely  dependent 
on  the  physical  qualities  of  the  substances  undergoing  absorption,  and 
especially  on  the  permeability  of  the  renal  cells  to  these  substances. 
The  physical  conditions  are,  however,  subordinated  to  the  physio- 
logical, so  that  a  salt  so  diffusible  as  potassium  iodide  is  left  in  the 
fluid,  while  sodium  chloride  may  be  reabsorbed  in  large  quantities. 

The  necessity  for  the  endowment  of  the  tubular  epithelium  with  a 
resorptive  as  well  as  a  secretory  function  is  determined  by  the  presence 
at  the  beginning  of  the  tubule  of  a  mechanism — the  glomerulus,  devoid 
of  the  fine  selective  power  or  chemical  sensibility  possessed  by  the  cells 
of  the  convoluted  tubules.  The  production  of  urine  by  the  glomerulus 
is  apparently  regulated  entirely  by  the  pressure  and  velocity  of  the 
blood  through  its  capillaries  and  by  the  colloid  content  of  the  blood- 
plasma.    We  may  assume  that  in  Bowman's  capsule  there  is  under 


THE   SECRETION   OF   URINE  1287 

normal  conditions  a  constant  production  of  a  fluid  free  from  protein, 
but  having  the  same  crystalloid  concentration  as  the  blood-plasma. 
With  any  rise  of  general  blood  pressure  the  amount  of  this  transudate 
is  increased;  with  any  fall  it  is  diminished.  The  small  qualitative 
changes  which  are  constantly  occurring  in  the  blood  as  the  result  of  the 
taking  of  food  or  the  activity  of  different  organs,  probably  produce  but 
little  effect  on  the  amount  of  glomerular  fluid.  Only  indirectly,  as  the 
result  of  these  events  on  the  general  blood  pressure,  or  possibly  in  con- 
sequence of  the  production  of  substances  having  a  vaso-dilator  effect 
on  the  renal  vessels,  will  the  amount  of  the  urine  turned  out  by  the 
glomeruli  be  affected.  These  structures  therefore  have  the  twofold 
function  of  regulating  the  total  amount  of  circulating  fluid  and  of 
providing  an  indifferent  fluid,  which  will,  so  to  speak,  flush  the  kidney 
tubules  and  carry  down  any  constituents  excreted  in  a  concentrated 
form  by  the  cells  of  these  tubules.  The  constant  production  of  a 
glomerular  transudate  might  result,  especially  in  terrestrial  animals, 
in  the  loss  to  the  organism  of  water,  or,  under  certain  nutritive  con- 
ditions, of  substances  indispensable  as  normal  constituents  of  the 
serum,  such  as  sodium  chloride,  which  could  not  be  made  good  at  the 
expense  of  the  food.  It  is  for  this  reason  that  an  absorptive  mechanism 
sensitive  to  and  reflecting  the  nutritive  condition  of  the  whole  body, 
especially  as  concerns  water  and  salts,  should  be  present  in  the  tubules. 
As  the  result  of  the  complementary  processes  of  absorption  and 
secretion  in  the  tubules,  the  michanging  glomerular  filtrate  undergoes 
great  modifications  in  its  passage  towards  the  ureter.  It  receives  urea, 
uric  acid,  phosphates,  and  under  certain  conditions  water,  from  the 
cells  of  the  convoluted  tubules.  It  gives  up  salts,  especially  sodium 
chloride,  and  generally  water  to  the  same  or  other  cells  of  the  tubules. 
So  that  finally,  instead  of  a  fluid  isotonic  with  the  blood  and  containing 
only  about  0-1  per  cent,  urea,  we  have  a  fluid  of  deep  yellow  colour, 
with  a  molecular  concentration  four  or  six  times  greater  than  that  ot 
the  blood,  and  containing  between  2  and  3  per  cent.  urea.  We  have  at 
the  present  time  no  means  of  judging  the  relative  Jtmoimts  of  fluid 
furnished  respectively  by  the  glomeruli  and  the  tubules  to  the  fully 
formed  urine.  It  is  probable  that,  under  ordinary  circumstances,  the 
processes  of  secretion  and  absorption  of  fluid  go  on  pari  passu  in  the 
urinary  tubules  just  as  they  do  in  the  mucous  membrane  of  the  smal' 
intestine.  The  demonstration  of  secretory  powers  in  the  cells  of  the  con- 
voluted tubules  relieves  us  from  the  necessity  of  the  assumption  made 
by  Ludwig  as  to  the  quantity  of  fluid  normally  turned  out  through  the 
glomeruU.  On  the  hypothesis  that  the  sole  function  of  the  tubules 
was  one  of  absorption,  and  that  all  the  urinary  constituents  were 
derived  from  the  glomerular  transudate,  thirty  htres  of  fluid  would 
have  to  be  filtered  through  the  glomeruli  in  order  to  excreto  the 


1288  PHYSIOLOGY 

30  grm.  urea  which  is  the  daily  output  of  a  man.  Of  these  thirty 
litres,  twenty-eight  litres  would  have  to  be  reabsorbed  in  the  tubules. 
Since  the  amount  of  blood  flowing  through  the  two  kidneys  in  a  man 
probably  varies  between  1600  and  1800  litres  in  the  twenty-four  hours, 
there  would  be  no  difficulty  in  the  production  of  such  an  amount  as 
thirty  litres,  which  would  only  represent  a  concentration  in  the  blood 
in  its  passage  through  the  glomeruli  of  under  2  per  cent.  The  secre- 
tion and  reabsorption  of  such  large  quantities  of  fluid  seem,  however, 
a  clumsy  way  of  arriving  at  a  urine,  whose  composition  should  be 
adapted  to  the  needs  of  the  animal ;  and  as  we  have  seen,  the  occur- 
rence of  an  actual  secretion  of  urea  by  the  cells  of  the  tubules  removes 
the  necessity  for  assuming  any  such  wasteful  proceeding.  It  is 
probable  that  the  actual  amount  of  the  glomerular  filtrate  in  the 
twenty-four  hours  may  not  exceed  to  any  large  extent  the  actual 
amount  of  urine  formed  by  the  whole  kidney  in  this  time. 


SECTION  III 

THE  PHYSIOLOGY  OF  MICTURITION 

The  urine  as  it  is  formed  passes  through  the  ureters  to  the  bladder, 
where  it  gradually  accumulates,  and  is  voided  at  intervals. 

The  ureters  are  muscular  tubes  lined  by  transitional  epithelium. 
The  muscular  coat  is  composed  of  three  layers  of  unstriated  fibres, 
a  middle  circular  coat  lying  between  external  and  internal  longitudinal 
coats.  If  the  ureter  be  exposed  in  the  living  animal,  contraction 
waves  are  seen  to  pass  along  its  muscular  coat  from  the  pelvis  of  the 
kidney  to  the  bladder,  driving  the  contained  fluid  in  front  of  them. 
The  frequency  of  the  contractions  is  increased  by  warming  the  m'eter, 
and  to  a  certain  extent  by  distension,  so  that  the  waves  are  more 
frequent  when  the  secretion  of  urine  is  profuse.  The  m'eters  enter  the 
bladder  at  or  near  its  base,  at  the  two  posterior  angles  of  the  region 
known  as  the  trigonum.  Their  entrance  is  oblique,  so  that  a  vahoilar 
orifice  is  formed,  which  effectively  prevents  reflux  of  urine  from  bladder 
to  ureter.  Ehythmic  waves  of  contraction  are  observed  also  iii  the 
excised  ureters,  wheii  these  are  kept  warm  in  normal  saline  solution. 
By  Engelmann  they  were  regarded  as  myogenic,  since  they  were 
present  in  the  middle  third  of  the  ureter,  which  he  imagined  to  be 
entirely  free  from  ganglion-cells.  As  a  matter  of  fact  ganglion-cells 
are  found  throughout  the  ureter,  though  in  larger  numbers  at  its  two 
ends.  The  ureters  are  supplied  with  nerve  fibres  from  the  splanchnic 
nerves  by  way  of  the  renal  plexus,  and  at  their  lower  ends  from  the 
hypogastric  nerves.  Stimulation  of  the  latter  as  a  rule  increases  the 
rhythm  of  the  contraction  presented  by  the  lower  end  of  the  m'eter. 
The  splanchnic  nerves  have  been  stated  to  produce  either  acceleration 
or  inhibition  of  the  contractions  at  the  upper  end  ;  their  action  is, 
however,  uncertain.  It  is  by  the  rhythmic  advancing  waves  of 
contraction  of  the  ureter  that  the  urine  is  continuously  passed  on  to 
the  bladder,  so  that  the  pelvis  of  the  kidney  is  kept  empty  of  fluid 
whatever  the  position  of  the  animal. 

The  bladder  is  lined  by  transitional  epithelium,  closely  adherent  to 
the  underlying  muscular  coat.  It  is  usual  to  describe  in  the  latter 
three  layers  of  muscular  fibres. : 

(1)  An  outer  layer  composed  of  bundles  running  longitudinally 
from  the  neck  of  the  bladder  to  the  fundus,  sometimes  distinguished 

1289 


1290  PHYSIOLOGY 

by  the  name  of  the  detrusor  urinw.  At  the  neck  of  the  bladder  these 
bundles  send  some  fibres  to  be  attached  to  the  pubes  as  the  pubo- 
vesical muscles.  On  the  dorsal  surface  some  bundles  in  the  male 
pass  on  to  the  prostate  and  the  urethra,  while  in  the  female  they  end  in 
the  tough  connective  tissue  in  the  urethro-vaginal  septum. 

(2)  The  middle  layer,  which  is  the  thickest  of  the  three,  is  composed 
of  fibres  arranged  circularly  and  forming  a  continuous  layer. 

(3)  The  inner  layer  is  thin  and  incomplete,  and  is  composed  of 
anastomosing  bundles  of  fibres  with  meshes  in  between  them  which 
are  covered  by  the  folds  of  the  mucous  membrane.  The  bundles  of 
fibres  run  freely  from  one  layer  to  the  other,  and  there  is  no  doubt  that 
the  name  of  detrusor  ought  physiologically  to  be  applied  to  the  whole  of 
the  three  coats,  which  act  as  one  in  diminishing  the  capacity  of  the 


Ureter-- 


Prosrete-- 
Memb.' 


Bulb 


Fig.  r).3r). 

bladder.  At  the  base  of  the  bladder  the  structure  of  the  wall  is 
modified  over  the  triangular  region  Ijnng  between  the  orifices  of  the 
ureters  and  of  the  urethra  (the  trigonum)  by  the  differentiation  here 
of  fibres  which  serve  as  a  sphincter  and  prevent  the  escape  of  urine. 
Over  the  trigonum  the  mucous  membrane  of  the  bladder  is  smooth  and 
closely  adherent  to  the  subjacent  muscular  fibres,  which  themselves 
are  much  more  closely  packed  than  the  rest  of  the  bladder  wall. 
From  these  muscular  fibres  the  most  important  sphincter,  the  sphincter 
trigoni,  is  formed.  Bundles  of  muscle  fibres  pass  from  the  trigonal 
muscle  obliquely  forwards  and  downwards  (the  individual  being  con- 
sidered in  the  erect  posture),  and  form  a  loop  around  the  orifice  of  the 
bladder,  lying  on  the  ventral  side  of  the  bladder  below  and  quite 
distinct  from  the  thick  coat  of  circular  fibres  belonging  to  the  bladder 
itself  (ss.  Fig.  535). 

This  sphincter  is  the  most  important  mechanism  for  the  retention 
of  urine.     If  a  catheter  be  passed  into  the  urethra  no  urine  escapes 


THK  PHY.STOLOOY  OF  MICTURITION  1291 

until  its  orifice  has  actually  entered  the  bladder.     The  wall  of  the 
urethra  is  surrounded  by  circular  muscular  fibres,  which,  by  their 


Ant.  long,  m 
Oiriuliir  niusf 

Pubo-vesi<:al  in. 
Sympliysis 


Ant.  circular  m. 
Ant.  loiip.  ni. 

f)s  pubis 
Sphincter  iirogenitaUs 


Circular 
Ixjngitudinal 


Os  pubis 


Circular  coat 
TA)ngitudinal  coat 
S/Jiincter  Irlgon! 

Prostate 


Circular  coat 
Longitudinal  coat 


Sphincter  trigoni 


Circular  coat 
Longitudinal'coat 

Sphincter  trigoni 
Longitudinal  muscle 

Fibre.-;  running  to  urotliro- 
vaginal  septum 


Fio.  536.     .Safjittal  sections  tliroiigli  ncvkof  bladder. 
(Metzner  after  Kalischek.) 
A,  in  middle  line  (male)  ;    B,  slightly  to  left  of  niiddlf    iini'  (inalc^  : 
o,  ditto  (female). 

tonic  contraction,  will  also  tend  to  prevent  the  escape  of  urine  along 
the  canal.  This  urethral  muscle  is  strengthened  by  two  sphincter 
muscles  which  are  voluntary  and  composed  of  striated  fibres.  The 
chief  one,  which  has  been  named  by  Kalischer  the  sphincter  urogenital^, 


1292 


PHYSIOLOGY 


but  is  better  known  as  the  compressor  urethrce,  forms  a  flat  ring  around 
the  second  part  of  the  urethra,  extending  in  the  male  from  the  prostate 
to  the  bulb,  where  its  function  is  taken  up  by  the  bulbo-cavernosus. 

The  bladder  is  therefore  supplied  with  a  powerful  muscular  wall, 
the  contraction  of  which  will  cause  its  evacuation,  and  with  sphincters 


Sup.  meg.  ganglioc 


Sup.  niPs.  nerve: 


Median  mes.  nerves 

Inf.  mes.  nerves> 

Inf.  mes.  ganglioi    - 

Hypogastric  nerves 


3rfl  lumb.  vert. 


Rectum — 


Bladder 


Hypogastric 

plexu^5 
Saeruni 

Sciatic  n. 

--Sacral  nerves 


Fio.  537.     Nerve  supply  to  bladder  of  cat.     (Nawrocki  and  Skabxtsciiewsky.) 

of  two  kinds,  one  involuntary,  the  sphincter  trujoni,  at  the  upper  neck 
of  the  bladder,  and  the  voluntary,  the  sphincter  urocjenitalis  and  bulbo- 
cavernosus  muscles,  which  can  empty  the  lower  parts  of  the  urethra. 

The  nerve-supply  of  the  bladder  (Fig.  537)  is  derived  from,  two  main 
sources,  namely,  from  the  upper  four  lumbar  nerves  through  the  sympa- 
thetic system,  and  from  the  second  and  third  sacral  nerves  by  means  of 
the  pelvic  visceral  nerves  ornervi  erigentes.    The  upper  lumbar  nerves 


THE  PHYSIOLOGY  OF  MICTURITION  1293 

send  white  rami  commuiiicantes  to  the  lateral  chain  of  the  sympathetic, 
and  thence  to  the  collateral  ganglia,  which  are  grouped  round  the 
inferior  mesenteric  artery  to  form  the  inferior  mesenteric  ganglion. 
Most  of  the  fibres  end  in  this  collection  of  ganglion-cells,  and  a  new  relay 
of  axons  passes  by  two  main  trunks,  the  hypogastric  nerves,  into  the 
pelvis  on  each  side  of  the  rectum  and  ends  in  a  plexus,  the  hypogastric 
plexus,  at  the  base  of  the  bladder.  From  this  plexus  fibres  pass  to  the 
bladder  wall.  The  pelvic  visceral  nerves  are  derived  from  the  second 
and  third  sacral  nerves.  They  make  no  connection  with  the  sym- 
pathetic system,  but  pass  directly  to  the  hypogastric  plexus  and  are 
carried  with  branches  of  this  plexus  to  the  neck  of  the  bladder.  The 
fibres  do  not  run  directly  from  the  spinal  cord  to  their  ending  in  the 
bladder  wall,  but  make  connection  with  cells  situated  peripherally, 
partly  in  the  hypogastric  plexus,  but  chiefly  in  the  walls  of  the  bladder 
itself.  Both  sets  of  fibres  supply  also  the  rectum  and  the  colon,  and 
carry  efferent  impulses  to  the  bladder.  Afferent  impulses  from  the 
bladder  travel  chiefly  in  the  pelvic  visceral  nerves. 

THE  FILLING  OF  THE  BLADDER 

Under  normal  circumstances  the  sphincters  at  the  neck  of  the 
l)ladder  are  in  a  state  of  tonic  contraction,  presenting  a  resistance  to 
the  emptying  of  this  organ  which  will  vary  according  to  their  degree 
of  contraction.  Thus  it  requires  a  considerably  greater  pressure  in 
the  bladder  to  overcome  the  resistance  of  the  sphincters  during  life 
than  after  death  of  the  animal.  In  some  cases  after  death  they  may 
permit  the  passage  of  urine  when  the  pressure  of  the  bladder  is  only 
about  20  mm.  water,  whereas  in  the  normal  animal  the  pressure  has 
as  a  rule  to  be  at  least  160  mm.  of  water  before  any  escape  takes  place. 
The  urine  therefore  as  it  is  secreted  must  accimiulate  and  distend  the 
l)ladder.  The  bladder  wall  reacts  to  a  distending  force  in  the  manner 
which  is  characteristic  of  all  muscular  tissue,  especially  unstriated. 
An  extending  force  ap])lied  to  an  unstriated  muscle  fibre  has  a  double 
elfect.  In  the  first  place,  if  the  stretching  force  is  applied  very  slowly, 
a  considerable  increase  in  length  of  the  muscle  may  occur  with  the 
application  of  a  very  small  amount  of  force.  If,  however,  the  force 
be  applied  more  rapidly,  the  sudden  increase  of  tension  acts  as  a  direct 
excitant  to  the  muscle,  causing  it  to  enter  into  contraction,  which  may 
be  tonic  or  rhythmic.  The  effect  of  the  entry  of  urine  into  the  empty 
bladder  on  the  tension  in  this  organ  will  depeiid  therefore  on  the 
rapidity  with  which  the  kidneys  are  secreting.  Under  normal  circimx- 
stances  micturition  occurs  in  man  when  the  intravesical  pressure  has 
risen  to  about  150  mm.  water.  Under  these  conditions  the  bladder 
will  contain  between  230  and  250  c.c.  of  urine.  If,  however,  the 
secretion  of  urine  has  occurred  very  rapidly,  the  same  pressure  may 


1294  PHYSIOLOGY 

be  attained  with  a  much  smaller  bladder  content,  and  if  the  bladder  be 
artificially  distended  by  the  injection  of  fluid  through  a  catheter,  50  c.c. 
of  fluid  may  suffice  to  raise  the  pressure  to  this  level.  As  the  urine  is 
slowly  secreted,  the  bladder  wall  at  first  gives  to  the  incoming  fluid, 
so  that  a  considerable  amount  can  be  stored  without  any  marked  rise 
of  pressure.  Later  on  the  pressure  begins  to  rise  more  rapidly,  and 
finally  attains  a  pressure  of  between  120  and  150  mm.  water.  At  this 
point  the  second  effect  of  the  stretching  of  the  muscular  wall  makes 
its  appearance.  A  manometer  connected  with  the  bladder  shows  a  series 
of  rhythmic  contractions  of  the  muscular  wall  (Fig.  538),  each  lasting 
about  a  minute,  at  first  shght  in  extent,  but  becoming  more  marked  as 
the  distension  of  the  bladder  augments.  In  a  bladder  entirely  cut  ofl 
from  its  connection  with  the  central  nervous  system  these  automatic 


U.B 


^AAA\M^MA^AAAAMAAAAAAAM^AA^M^AJW^V^AAAAMMM^^ 

Fig.  538.     Tracings  of  rhythmic  contractions  of  urinary  bladder. 
(Shereixgton.) 

rhythmic  contractions  gradually  increase  in  force  until  one  of  them 
suffices  to  overcome  the  resistance  presented  by  the  tonically  con- 
tracted sphincter.  A  partial  emptying  of  the  bladder  therefore  takes 
place,  but  the  pressure  falls  below  that  necessary  to  overcome  the 
resistance  of  the  sphincter  before  the  bladder  has  been  quite  emptied, 
so  that  there  is  always  under  these  circumstances  a  certain  amount  of 
residual  urine  left  in  the  bladder.  This  is  the  condition  found  in 
animals  where  the  lower  part  of  the  spinal  cord  has  been  extirpated, 
or  in  man  where  the  same  part  of  the  central  nervous  system  has  been 
destroyed  as  the  result  of  accident  or  disease. 

THE  MECHANISM  OF  EVACUATION  OF  THE  BLADDER 

In  the  denervated  bladder  the  factor  finally  causing  partial 
evacuation  is  the  gradual  increase  in  the  intravesical  tension  from  the 
accumulation  of  fluid  in  this  viscus.  The  same  factor  is  prepotent  in 
determining  the  onset  of  normal  micturition  in  an  animal  with  the 
nervous  connections  of  its  bladder  intact.  Apart  from  the  control  of 
the  higher  centres,  micturition  will  take  place  each  time  that  the  tension 


THE  PHYSIOLOGY  OF  MICTURITION  1295 

in  the  bladder  has  reached  a  certain  height,  i.e.  about  15  cm.  water, 
the  amount  of  fluid  in  the  bladder  at  the  time  depending,  on  the  one 
hand  on  the  rate  at  which  the  fluid  has  entered  this  organ  from  the 
ureters,  on  the  other  hand  on  the  irritability  of  the  bladder  wall 
itself  and  of  the  nervous  centres  concerned  with  its  motor  innervation. 
The  effect  of  the  gradual  accumulation  of  fluid  and  rise  of  tension  is 
twofold.  In  the  first  place,  it  acts  on  the  bladder  wall,  causing 
rhythmic  contractions  of  ever-increasing  intensity  ;  in  the  second 
place,  the  mere  stretching  of  the  bladder  originates  impulses  in  the 
sensory  nerve-endings  in  its  wall,  which  are  reinforced  at  every 
rise  of  tension  caused  by  the  rhythmic  contractions.  These 
impulses  travel  up  to  the  spinal  centres,  and  are  summated  until 
they  result  in  a  sudden  discharge  of  efferent  impulses  of  two  kinds, 
namely  : 

(1)  Motor  impulses  to  the  whole  musculature  of  the  fundus  of  the 
bladder  (the  detrusor  in  its  widest  sense) ; 

(2)  An  inhibition  of  the  tonic  contraction  of  the  sphincter.  This 
inhibition  may  be  determined  by  inhibitory  impulses  travelling  to 
the  sphincter  and  causing  its  relaxation,  or  by  the  central  inhibition 
of  the  impulses  normally  going  to  the  sphincter  and  maintaining  its 
tonic  contraction.  The  resultant  of  these  two  processes,  the  contrac- 
tion of  the  detrusor  and  the  relaxation  of  the  sphincter,  is  a  complete 
emptying  of  the  bladder,  and  the  act  is  completed  by  the  contraction 
of  the  involuntary  and  voluntary  muscles  surrounding  the  urethra 
and  causing  complete  expulsion  of  the  contents  of  this  tube. 

THE  INNERVATION  OF  THE  BLADDER 
ACTION  OF  THE  PELVIC  VISCERAL  NERVES.  In  all  animals 
excitation  of  the  peripheral  end  of  one  pelvic  visceral  nerve  causes  a 
strong  contraction  of  the  same  side  of  the  bladder,  involving  all  its 
coats  and  sometimes  extending  to  a  slight  extent  to  the  contralateral 
half  of  the  bladder.  When  both  pelvic  nerves  are  stimulated  simul- 
taneously contraction  of  both  sides  of  the  bladder  causes  a  consider- 
able rise  of  pressure  in  its  interior  (Fig.  539)  which  is  always  sufficient  to 
overcome  the  resistance  of  the  sphincter  and  to  cause  a  complete  empty- 
ing of  the  bladder.  There  is  no  doubt  therefore  that  these  nerves  are 
the  most  important  for  the  act  of  micturition.  As  to  the  action  of  these 
nerves,  however,  on  the  sphincter  the  results  of  different  experi- 
menters are  somewhat  at  variance.  In  the  cat  there  seems  to  be  no 
doubt  that  inhibition  of  the  sphincter  may  result  from  stimulation  of 
the  pelvic  visceral  nerves.  On  the  other  hand,  Fagge,  working  on  the 
dog,  foimd  tlat  although  micturition  was  excited  by  the  stimulation 
of  these  nerves,  the  expulsion  of  urine  did  not  occur  until  the  intra- 
vesical tension  had  reached  the  point  at  which  the  resistance  of  the 


1296  PHYSIOLOGY 

sphincter  could  be  overcome  without  any  alteration  of  its  state  of  con- 
traction, i.e.  the  point  at  which  fluid  injected  into  the  bladder  through 
the  ureter  began  to  escape  from  the  urethra  without  stimulation  of 
any  nerves  whatever. 

Observations  on  man  would  support  the  view  that  an  active 
relaxation  of  the  sphincter  trigoni  is  a  necessary  part  of  the  act  of 
micturition.  Thus  in  experiments  by  Reyfisch  a  rigid  catheter  was 
introduced  into  the  bladder,  which  was  fully  distended  with  fluid. 
On  withdrawing  the  catheter  until  its  opening  lay  just  outside  the 
bladder  in  the  posterior  urethra,  the  flow  of  urine  stopped.  The 
man,  however,  was  able  to  micturate  directly  he  was  told  to,  and  to 
stop  again  at  will     It  was  impossible  in  this  case  for  any  of  the 


Fig.  539.     Curve  showing  rise  of  pressure  in  the  bladder  caused  by  stimulation 

of  s,  sacral  nerves  ;  h,  hypogastric  nerves.     (Fagge.) 

The  scale  indicates  centimetres  of  water. 

urethral  muscles  to  be  concerned,  since  the  rigid  catheter  impeded 
their  action.  The  relaxation  of  the  sphincter  must  therefore  be 
brought  about  by  impulses  descending  the  pelvic  visceral  nerves, 
which  we  may  regard  as  motor  to  the  '  detrusor  '  and  inhibitory  to  the 
sphincter  of  the  bladder. 

Section  of  the  nerve  on  one  side  causes  no  abnormality  in  mic- 
turition. After  three  weeks,  stimulation  of  the  intact  nerve  causes 
contraction  of  the  ivhole  bladder,  owing  to  the  outgrowth  of  pre- 
ganglionic fibres  from  the  sound  trunk  to  the  decentralised  ganglia  of 
the  opposite  side  (Elliott).  Section  of  both  nerves  paralyses  micturi- 
tion, but  power  of  partial  evacuation  of  the  bladder  may  return  in  a 
few  weeks.  If  now  the  hypogastrics  be  cut,  or  even  the  sacral  cord 
extirpated,  the  bladder  is  not  completely  paralysed,  but  its  evacua- 
tion becomes  unconscious  and  incomplete. 

ACTION  OF  THE  HYPOGASTRIC  NERVES.  These  nerves,  which 
are  derived  from  the  sympathetic  system,  show  marked  differences 


THE  PHYSIOLOGY  OF  MICTURITION  1297 

in  their  action,  according  to  the  animal  which  is  the  subject  of 
investigation.  In  the  dog  the  hypogastric  nerves  cause  a  strong  con- 
traction of  the  muscle  fibres  at  the  base  of  the  bladder,  especially  of 
the  trigonum  and  of  the  sphincter  trigoni.  When  these  nerves  are 
stimulated  simultaneously  with  the  pelvic  visceral  nerves  a  great  rise 
of  intravesical  tension  may  be  induced  without  any  flow  of  urine  taking 
place.  In  some  cases  prolonged  stimulation  of  these  nerves  in  the  dog 
causes  apparently  an  active  relaxation  of  the  sphincter  of  the  bladder. 
On  the  other  hand,  in  the  rabbit  and  the  cat  these  nerves  cause 
an  inhibition  of  the  bladder  wall.  In  other  animals  they  may  excite 
either  contraction  or  relaxation  (or  both)  of  the  detrusor.  They  always 
contain  motor  fibres  to  the  sphincter  of  the  bladder  as  well  as  to  the 
constrictor  fibres  surrounding  the  urethra.  Where  this  effect  is  tonic, 
micturition  must  be  associated  with  a  central  inhibition  of  their 
tonic  activity.  On  the  other  hand,  the  retention  of  urine  and  the 
distension  of  the  bladder  may  be  aided  by  a  reflex  dilatation  of  the 
bladder  wall  and  a  reflex  constriction  of  the  sphincter  in  each  case 
excited  through  these  nerves.  Normally  therefore  both  sets  of  nerves 
are  called  into  play.  The  hypogastrics  play  an  especially  active  part 
during  the  accumulation  of  urine  in  the  bladder,  while  the  pelvic 
visceral  nerves  are  necessary  for  the  complete  evacuation  of  the  bladder 
which  occurs  at  micturition. 

THE  CENTRAL  CONTROL  OF  THE  BLADDER 

The  nerve-centre  which  presides  over  the  tonus  and  contraction 
of  the  bladder  is  situated  in  the  lumbo-sacral  spinal  cord.  If  this 
centre  and  its  connections  be  intact,  micturition  may  be  carried  out 
normally  even  after  section  of  the  cord  in  the  dorsal  region.  The 
centre  can  be  excited  reflexly  by  stimulation  of  almost  any  sensory 
nerve,  such  as  the  sciatic  or  the  fifth  nerve.  In  many  cases  where, 
in  consequence  of  obstruction  to  the  passage  of  impulses  from  the 
higher  parts  of  the  central  nervous  system,  micturition  is  delayed, 
this  act  may  be  excited  by  the  application  of  cold  or  hot  sponges 
to  the  perineum,  and  it  is  well  known  that  almost  any  irritation  of 
the  pelvic  organs  in  children  may  give  rise  to  reflex  involuntary 
mictm'ition. 

In  the  adult  the  processes  of  retention  and  evacuation  of  urine  are 
modified  and  controlled  by  voluntary  effort.  The  normal  action  of 
the  sphincter  mechanism  may  be  aided  by  the  contraction  of  the 
perina)al  muscles  which  keep  the  urethra  closed.  The  reflex  process 
of  evacuation  may  be  set  in  motion  by  voluntary  c-ontraction  of  the 
abdominal  muscles,  by  which  the  pressure  in  the  bladder  is  increased 
and  the  normal  sphincter  action  overcome.  It  is  probable  too  that 
the    individual  has   a   certain  degree   of  voluntary  power   over  the 

82 


1298  PHYSIOLOGY 

unstriated  muscles  of  the  bladder,  and  that  the  contraction  of  the 
muscular  wall  may  be  directly  augmented  by  impulses  proceeding 
from  the  cortex  to  the  upper  part  of  the  lumbar  cord.  This  view 
is  favoured  by  the  fact  that  stimulation  of  the  crus  cerebri  has 
been  observed  to  cause  contraction  of  the  detrusor  urinse.  In  this 
experiment  the  abdomen  was  opened,  so  there  could  be  no  question 
of  the  contraction  of  the  abdominal  muscles. 


CHAPTER  XVIII 

THE  SKIN  AND  THE  SKIN-GLANDS 

In  all  classes  of  animals  the  skin  performs  two  functions.  In  the  first 
place,  it  serves  to  protect  the  more  delicate  underlying  parts  from 
injury  and  from  penetration  or  invasion  by  foreign  organisms.  In 
the  second  place,  it  serves  as  a  sense-organ,  and  is  richly  supplied  with 
nerves,  by  means  of  which  the  activities  of  the  body  as  a  whole  may 
be  brought  into  relation  with  the  changes  going  on  in  the  environ- 
ment and  affecting  the  external  surface  of  the  body.  In  warm-blooded 
animals  the  skin  plays  an  important  part  in  the  regulation  of  the  body 
temperature,  since  the  loss  of  heat  to  the  body  must  occur  almost 
entirely  through  its  surface.  In  the  present  chapter  we  have  to 
deal  only  with  the  first  and  third  of  these  functions. 

The  development  of  the  skin  as  an  organ  of  protection  shows  wide 
modification  in  various  classes  of  animals.  Thus  it  may  become  the 
seat  of  formation  of  horny  plates,  as  in  the  alligator  ;  of  poisonous 
glands,  as  in  the  toad  ;  or  of  mucous  glands,  as  in  many  varieties 
of  fishes.  In  warm-blooded  animals  the  development  of  hair  from  the 
deeper  layers  of  the  epidermis  serves  to  diminish  the  loss  of  heat.  Since 
the  hair-follicles  are  richly  supplied  with  nerve  fibres,  the  hairs  act 
also  as  organs  of  sensation.  In  man,  where  the  hairs  are  rudimentary, 
except  in  certain  localities,  practically  only  this  tactile  function  is 
retained.  The  external  layer  of  the  skin  in  man  consists  of  a  tough 
horny  layer  formed  by  the  keratinisation  of  the  external  layers  of 
cells  of  the  epidermis.  The  skin  is  composed  of  two  parts,  the  epidermis 
and  the  cutis  (Fig.  540).  The  epidermis  is  a  stratified  squamous 
epithelium.  The  deeper  layers  form  the  rete  mucosum,  being  soft  and 
protoplasmic,  while  the  superficial  layers  forming  the  cuticle  are  hard 
and  horny.  The  most  superficial  layer  of  the  rete  mucosum  is  formed 
of  flattened  cells  filled  with  granules  of  a  material  staining  deeply 
with  hsematoxylin  and  eosin,  known  as  eleidin.  This  layer  is  called 
the  stratum  granulosum.  Immediately  superficial  to  this  layer  is 
another  in  which  the  colls  are  indistinct.  Tlio  colls  are  clear  in  section 
and  form  what  is  known  as  the  strntuni  Iiiriduni.  These  two  layers 
evidently  form  the  intermediate  stages  in  tho  transformation  of  the 
cells  of  tlie  rete  mucosum  into  the  horny  scales  which  make  up  the 
superficial  cuticle.     The  cutis  or  corium  is  composed  of  dense  connec- 

1299 


1300 


PHYSIOLOGY 


tive  tissue,  which  becomes  more  open  in  texture  in  its  deeper  part, 
where  it  merges  into  the  subcutaneous  connective  tissue.  The  most 
superficial  layer  of  the  corium  is  prolonged  into  minute  papillae  over 
which  the  epidermis  is  moulded.  These  papillae  contain  for  the  most 
part  capillary  vessels  ;  a  few  contain  touch  corpuscles,  special  organs 
of  tactile  sensation.  The  blood-vessels  of  the  skin  form  a  close  capillary 
network  immediately  at  the  surface  of  the  cutis,  sending  up  loops 
into  the  papillae.     All  parts  of  the  skin,  except  the  palms  of  the  hands 


stratum 
conieum 

Str<atum 
lucidum 

Stratum 
granulosum 


Cutis  vera 


Fig.  540.  Vertical  section  through  the  skin  of  the  palmar  side  of  the  finger,  show- 
ing two  papillae  (one  of  which  contains  a  tactile  corpuscle)  and  the  deeper 
layer  of  the  epidermis.     Magnified  about  200  diameters.     (Schafer). 


and  the  soles  of  the  feet,  are  beset  with  hair-follicles.  The  hair- 
follicles  are  small  pits  which  extend  downwards  into  the  deeper  part 
of  the  corium,  being  down-growths  of  the  rete  mucosum.  The  hair 
grows  from  a  small  papilla  of  cells  at  the  bottom  of  the  follicle,  the 
part  of  the  hair  lying  within  the  follicle  being  known  as  the  hair-root. 
The  hair  itself  consists  of  long  tapering,  horny  cells,  the  nuclei  of 
which  are  still  visible,  though  the  cell  substance  has  been  almost 
entirely  converted  into  keratin. 

In  order  to  keep  the  cuticle  supple  and  preserve  it  from  the  drying 


THE  SKIN  AND  THE  SKIN-GLANDS  1301 

effects  of  the  atmosphere,  it  is  kept  constantly  impregnated  with  a 
fatty  material  known  as  sebum.  This  material  is  formed  by  the 
sebaceous  glands,  which  are  distributed  all  over  the  surface  of  the  skin 
wherever  hair-follicles  are  to  be  found,  the  mouths  of  the  glands 
opening  into  the  hair-follicles.  A  sebaceous  gland  is  a  pear-shaped 
body,  consisting  of  a  secreting  part  and  a  short  neck,  opening  into 
the  follicle.  The  gland  proper  is  composed  of  a  solid  mass  of  cells. 
The  outermost  cells  are  flattened  and  generally  show  signs  of  pro- 
liferation. The  cells  lying  internal  to  these  are  much  larger,  and 
their  protoplasm  is  transformed  into  a  network  in  the  meshes  of 
which  are  granules  which  may  show  the  reaction  of  fat.  Further 
inwards  the  protoplasmic  network  diminishes  in  amount,  while  the  fatty 
granules  increase  in  size,  so  that,  in  the  lumen  adjoining  the  duct, 
we  find  only  a  mass  of  cell  debris  and  masses  of  fatty  material.  It 
has  often  been  thought  that  the  secretion  of  sebum  depended  simply  on 
a  fatty  degeneration  of  the  cells.  The  granules,  however,  when  they 
fii'st  appear,  stain  with  acid  fuchsin  rather  than  osmic  acid,  and  one 
must  regard  the  formation  of  sebum  as  an  act  of  true  secretion  in 
which  the  secretory  granules  are  gradually  transformed  into  the  special 
constituents  of  the  sebum.  For  it  must  be  noted  that  the  sebum  is 
not  a  true  fat,  nor  does  it  correspond  in  composition  with  the  fat  found 
in  other  parts  of  the  body.  It  is  true  that  it  contains  fatty  acids, 
but  these  are  for  the  most  part  in  combination,  not  with  glycerin,  but 
with  higher  alcohols,  including  cholesterol.  A  somewhat  similar 
material  may  be  extracted  from  wool,  and  is  known  as  wool-fat 
or  lanoline,  as  well  as  from  the  feather-glands  of  water  birds, 
such  as  the  goose  and  duck.  It  must  be  regarded  rather  as  a  wax 
than  a  fat.  It  presents  many  advantages  over  ordinary  fat  as  a  pro- 
tective salve  for  the  surface  of  the  body.  In  the  first  place,  it  can 
take  up  a  large  amount,  as  much  as  100  per  cent.,  of  water.  In  the 
second  place,  it  is  not  attacked  by  micro-organisms,  so  that  it  does  not 
tend  to  become  rancid  or  to  furnish  a  nidus  for  the  growth  of  these 
organisms  on  the  surface  of  the  body. 

The  secretion  of  sebum  is  a  continuous  process,  though  it  is  probably 
quickened  in  conditions  of  increased  vascularity  of  the  skin.  The 
extrusion  of  the  products  of  secretion  is  determined  by  the  presence 
of  unstriated  muscle  fibres,  the  arrector  pili,  which  pass  from  the 
surface  of  the  cutis  obliquely  to  the  outer  surface  of  the  sebaceous 
gland.  When  these  muscle-fibres  contract  the  hair  is  erected  and  a 
certain  amount  of  the  sebum  squeezed  out  on  to  the  root  of  the  hair 
and  the  surrounding  skin.  This  contraction  will  occur  whenever  cold 
is  suddenly  applied  to  the  skin.  The  contracted  condition  of  all 
the  muscles  of  the  hair-follicles  is  shown  by  the  '  goose-skin  '  produced 
under  such  circumstances.     There  is  no  evidence  that  the  secretion 


1302  PHYSIOLOGY 

of  sebum  is  in  any  way  under  the  control  of  the  central  nervous 
system. 

THE  SWEAT-GLANDS.  Under  normal  circumstances  in  tem- 
perate climates  the  greater  part  of  the  water  taken  in  with  the  food  in 
the  course  of  the  day  is  excreted  by  the  kidneys,  a  smaller  proportion 
leaving  by  the  lungs  and  by  the  surface  of  the  skin.  On  an  average 
we  may  say  that  about  700  c.c.  are  got  rid  of  through  the  skin.  The 
excretion  of  water  by  the  skin  is,  however,  mainly  determined  by  the 
need  for  regulating  the  temperature  of  the  body,  so  that  the  amount 
leaving  in  this  way  depends  entirely  on  the  heat  production  of  the  body 
or  on  the  external  "temperature,  and  is  very  little  affected  by  alterations 
in  the  quantity  of  fluid  drunk.  A  certain  amount  of  water  is  con- 
stantly evaporated  from  the  surface  of  the  body  as  the  so-called  '  in- 
sensible perspiration.'  If  a  man's  body  be  enclosed  in  a  vessel  through 
which  a  current  of  air  is  passed,  and  the  temperature  of  the  air  gradually 
raised,  it  will  be  noted  that  the  amount  of  water  given  off  rises  slowly 
up  to  a  certain  degree  and  then  rises  rapidly.  The  sudden  kink  in  the 
curve  is  due  to  the  setting  in  of  the  activity  of  the  sweat-glands,  and 
we  are  therefore  justified  in  regarding  the  insensible  perspiration  as 
being  determined  by  evaporation  of  water  from  the  surface  of  the  cuticle 
itself  apart  altogether  from  the  sweat-glands.  The  sweat-glands, 
which  are  distributed  over  the  whole  surface  of  the  skin,  are  especially 
abundant  on  the  palm  of  the  hand  and  on  the  sole  of  the  foot.  They 
are  composed  of  single  unbranched  coiled  tubes,  which  lie  in  the  sub- 
cutaneous tissue  and  send  their  ducts  up  through  the  cutis,  to  open 
on  the  surface  by  corkscrew-like  channels  which  pierce  the  epidermis. 
The  secreting  part  of  the  tube  consists  of  a  basement  membrane  lined 
by  a  double  layer  of  cells  ;  the  innermost  of  these  are  cubical  and 
represent  the  secreting  cells  proper.  Between  the  secreting  cells  and 
the  basement  membrane  is  a  layer  of  unstriated  muscle  fibres.  The 
duct  of  the  gland  has  an  epithelium,  consisting  of  two  or  three  layers  of 
cells  with  a  well-marked  internal  cuticular  lining,  but  there  is  no 
muscular  layer. 

The  sweat  formed  by  these  glands  is  the  most  dilute  of  all  animal 
fluids.  As  collected  it  generally  contains  epithelial  scales  and  some 
admixture  of  sebima.  After  filtration  it  forms  a  clear  colourless  fluid 
of  a  specific  gravity  of  about  1003.  It  contains  over  99  per  cent,  of 
water.  Among  the  solid  constituents  sodiimi  chloride  is  the  most 
prominent — ^it  may  contain  from  0-3  to  0-5  per  cent,  of  this  salt.  It  is 
generally  hypotonic  as  compared  with  the  blood-plasma.  It  may 
also  contain  small  traces  of  proteins.  This  constituent  is  especially 
marked  in  the  horse.  It  generally  contains  also  a  small  quan- 
tity of  urea,  which  may  become  a  prominent  constituent  in  cases  of 
renal  disease.     The  quantity  of  sweat  excreted  in  the  day  is  very 


THE  SKIN  AND  THE.  SKIN-GLANDS  1303 

variable.  The  secretion  is  under  the  control  of  the  central  nervous 
system  and  is  ahnost  entiri'ly  adapted  to  the  re<j;ulation  of  the  body 
temperature.  The  nervous  mechanism  can  be  set  into  activity  eitlier 
centrally  or  reflexly.  'I'he  most  usual  factor  is  a  rise  of  the  body 
temperature.  If  a  man  sit  in  a  warm  room,  e.f/.  of  a  Turkish  bath, 
the  secretion  of  sweat  commences  as  soon  as  the  temperature  of  the 
body  has  attained  a  height  of  0-5"'  to  1  C.  above  normal.  In  the  case 
of  muscular  exercise  the  temperature  will  generally  be  found  to  be 
raised  if  it  be  taken  at  the  instant  that  sweating  has  commenced. 
The  effect  of  rise  of  temperature  may,  however,  be  either  local  or  central, 
so  that  one  arm  enclosed  iji  a  hot-air  bath  may  sweat  while  the  rest 
of  the  body  is  dry.  Under  ordinary  circumstances  the  central 
stimulation  by  the  warm  blood  is  the  predominant  factor.  This  is 
shown  by  an  experiment  of  Luchsinger.  In  the  cat  sweating  is  to  be 
observed  only  on  the  hairless  pads  of  the  front  and  hind  paws.  If  one 
sciatic  nerve  be  cut  and  the  animal  be  placed  in  a  warm  chamber, 
sweating  will  commence  as  the  temperature  of  the  animal  rises  in  the 
three  intact  paws,  while  the  paw  with  the  nerve  cut  will  be  quite  dry. 
Sweating  moreover,  as  has  been  shown  by  Kahn,  may  be  induced  in 
the  cat's  paws  by  warming  the  blood  passing  through  the  carotid 
arteries  on  its  way  to  the  brain,  at  a  time  when  the  temperature  of  the 
blood  circulating  through  the  rest  of  the  body,  including  the  paws 
themselves,  has  undergone  no  alteration.  Sweating  may  also  be 
aroused  by  asphyxia,  and  this  result  is  found  even  in  the  spinal  cat, 
i.e.  after  separation  of  the  spinal  centres  from  the  medulla.  The 
secretion  of  sweat  resulting  from  stimulation  of  the  sweat-nerves, 
although  generally  associated  with  increased  vascularity  of  the  skin, 
is  not  in  any  way  dependent  thereon.  Thus  even  in  the  amputated 
limb  stimulation  of  the  sciatic  nerve  may  cause  the  appearance  of 
drops  of  sweat  on  the  pad  of  the  foot.  If  the  sciatic  nerve  be  stimu- 
lated in  the  intact  animal,  the  secretion  of  sweat  which  is  produced 
is  associated  with  constriction  of  the  vessels  of  the  skin,  due  to  simul- 
taneous stimulation  of  the  vaso-constrictor  nerves  running  in  the 
sciatic  nerve. 

As  Langley  has  shown,  the  sweat-nerves  run  entirely  in  the  sympa- 
thetic system.  Leaving  the  cord  by  the  white  rami  communicantes 
from  the  second  dorsal  to  the  third  or  fourth  lumbar  nerves,  they 
pass  into  the  sympathetic  chain.  Here  the  first  relay  of  fibres  ends  in 
connection  with  the  cells  of  the  sympathetic  ganglia,  and  a  fresh  relay 
of  fibres,  which  are  non-medullated,  pass  from  the  cells  along  the 
grey  rami  into  the  various  spinal  nerves,  to  be  distributed  to  the  whole 
surface  of  the  skin.  The  secretion  of  sweat  by  the  sweat-glands  may 
be  roused  by  the  injection  of  pilocarpine  even  after  division  of  the 
sweat-nerves,  so  that  this  drug  must  act  peripherally  on  the  glands. 


1304  PHYSIOLOGY 

The  action  of  pilocarpine,  as  well  as  the  effects  of  artificial  stimulation 
of  the  sweat-nerves,  is  abolished  by  the  administration  of  atropine. 

THE  GASEOUS  EXCHANGES  OF  THE  SKIN.  In  any  animal 
with  a  thin  moist  skin,  such  as  the  frog,  the  absorption  of  oxygen  and 
the  excretion  of  CO2  from  the  skin  may  be  sufficient  for  the  proper 
aeration  of  its  blood,  so  that  it  may  continue  to  live  after  the 
extirpation  of  its  lungs.  In  man  there  is  also  a  continuous  output 
of  CO2  through  the  skin,  but  the  amount  leaving  the  body  in  this 
j\^ay  is  neghgible  compared  with  that  which  is  exhaled  through  the 
lungs.  The  loss  of  COg  by  the  skin  rises  with  increase  of  external 
temperature.  Thus  at  a  temperature  of  29°  to  33°  C.  the  COg  output 
by  the  skin  is  about  0-35  grm.  per  hour,  i.e.  about  84  grm.  in  the 
twenty-four  hours.  When  the  external  temperature  rises  above 
33°  C,  the  CO2  output  increases,  so  that  at  34°  it  is  doubled  and  at 
38-5°  it  may  amount  to  as  much  as  1-2  grm.  per  hour  (Schierbeck). 
It  is  just  at  this  temperature  of  33°  C.  that  a  secretion  of  sweat 
begins  to  be  noticeable,  so  it  has  been  suggested  that  the  increased 
CO2  output  may  be  due  directly  to  the  increased  work  and  metabolism 
of  the  sweat-glands  during  their  activity. 

ABSORPTION  BY  THE  SKIN.  In  order  to  test  the  alleged 
influence  of  baths  containing  medicinal  substances  in  solution,  many 
experiments  have  been  made  to  determine  whether  absorption  is  possible 
by  the  skin.  It  may  be  regarded  as  established  that  the  uninjured 
skin  is  impermeable  for  watery  solutions  of  salts  or  other  substances. 
On  the  other  hand,  it  is  possible  to  produce  a  certain  amount  of 
absorption  by  the  inunction  of  substances  dissolved  in  fatty  vehicles. 
Thus  the  administration  of  mercury  is  often  carried  out  by  the 
inunction  of  mercurial  ointments,  and  the  fact  that  mercurial  salivation 
may  be  produced  in  these  conditions  shows  that  a  certain  amount  of 
the  mercury  must  have  been  absorbed.  It  is  difficult  to  imagine  that 
any  appreciable  amount  of  cod  liver  oil  will  be  available  for  the 
nutrition  of  the  infant  when  this  substance  is  administered  by  rubbing 
it  on  the  skin.  On  the  other  hand,  the  moist  mucous  surfaces,  such  as 
the  conjunctiva  or  the  mucous  membrane  of  the  respiratory  passages, 
as  well  as  raw  surfaces  of  the  skin,  e.g.  which  have  been  deprived  of  their 
epidermal  layer  by  the  application  of  blisters,  permit  of  the  rapid 
passage  of  substances  in  watery  or  oily  solution. 


CHAPTER  XIX 

THE  TEMPERATURE  OF  THE  BODY  AND  ITS 
REGULATION 

In  dealing  with  the  chemical  changes  in  the  body  as  a  whole  we  have 
seen  that  the  sum  of  the  metabolic  processes  is  associated  with  the 
evolution  of  heat.     In  man,  under  normal  circumstances,  while  doing 


TCMPERATUnC 

Fia.  541.     Eifcct  of  temperature  on  the  CO.^  output  of  a  lupin  seedling. 

Orclinates  =  milligrammes  CO.^  per  hour.    Abscissae  =  temperature  in  degrees 

Centigrade. 

moderate  work,  the  total  energy  requirements  amount  to  about  3000 
calories.  The  whole  of  this  is  derived  from  the  oxidation  of  the 
food,  the  combination  of  its  carbon  and  hydrogen  with  oxygen  to 
form  (.'Oo  and  water,  with  the  evolution  of  the  corresponding  amount  of 
energy.  Of  this  energy  only  a  small  proportion,  on  the  average  about 
one-twentieth,  leaves  the  body  as  mechanical  energy,  the  rest  being 
evolved  in  the  form  of  heat  and  being  expended  in  the  maintenance  of 
tlic  bodv  temperature,  or  in  the  warming  of  the  surrounding  medium. 

1305 


1306 


PHYSIOLOGY 


The  evolution  of  heat  is  not  confined  to  the  higher  animals,  but 
is  common  to  all  li\'ing  beings.  It  is  very  evident,  for  instance,  in  the 
germination  of  peas  or  barley.  The  atmosphere  of  a  bee-hive  is  often 
ten  degrees  above  that  of  the  surrounding  atmosphere.  Whenever 
we  can  excite  increased  activity  in  an  organ,  we  ai'e  able  to  show, 
except  in  the  single  case  of  the  nerve  impulse,  that  such  acti\aty  is 
associated  with  the  evolution  of  heat.  This  heat  is  derived  from  the 
chemical  changes  which  proceed  in  the  li\'ing  cells.  Since  all  chemical 
processes  are  quickened  by  rise  of  temperature,  we  should  expect  to 
find  that  the  heat  produced  in  the  metabolic  processes  of  organisms 
would  tend  in  itself  to  quicken  these  processes.  In  most  chemical 
reactions  a  rise  of  about  10'  C.  would  increase  the  velocity  of  reaction 
from  two  and  a  half  to  three  times,  and  the  same  rule  is,  within  the 
limits  of  stabihty  of  living  tissues,  found  to  hold  good  for  them  also. 
The  diagram  (Fig.  541)  shows  the  influence  of  temperature  on  the 
chemical  changes  in  a  lupin  seedling  as  measured  by  the  output  of 
CO2  per  hour  per  100  grm.  of  plant.  A  marked  increase  in  the  rate  of 
chemical  decomposition  is  shown  to  follow  a  rise  of  temperature  ;  but, 
about  -40"  C.  the  rate  of  change  is  at  an  optimum,  and  thereafter 
rapidly  declines,  owing  to  the  fact  that  the  living  tissues  are  being 
killed  by  the  excessive  temperature. 

Hence  in  the  animal  organism  we  shall  expect  to  find  that  the  rate 
of  the  metabolism  is  also  proportional  to  the  temperature  of  the  animal. 
This  is  universally  the  case  whether  we  are  deahng  with  warm-blooded 
or  cold-blooded  animals.  In  •  cold-blooded  '  animals  the  temperature  of 
the  body,  and  therefore  the  rate  of  its  metabohsm  and  the  amount  of 
its  heat  production,  is  proportional  to  the  external  temperature 
(Fig.  542).  The  following  Table  gives  the  average  COo  output  per  hour 
of  five  lizards  placed  in  a  chamber  which  could  be  maintained  at 
varying  temperature  : 


Temperature 

Temperature  of 

COo  produced 

of  bath 

lizards  (average) 

in  one  hour 

oU=  C. 

5-5=  C. 

•0246 

9-0=  C. 

9-2°  C. 

•0790 

150°  C. 

15-2°  C. 

•0981 

20o=  C. 

20-4°  C. 

•1023 

25-0°  C. 

24-5°  C. 

•1193 

300°  C. 

29-3°  C. 

•1440 

350°  C. 

34-8°  C. 

•1814 

390°  C. 

38-5°  C. 

•5454 

It  might  be  thought  that^uch  a  reaction  in  change  of  tempera- 
ture would  result  in  a  vicious  circle.     Since  the  animal  is  continually 


THE  TEMPERATURE  OF  THE  BODY 


1307 


producing  heat  and  thus  raising  its  temperature  above  that  of  its 
suirouiidings,  one  might  expect  to  find  that  the  hij^her  the  external 
temperature  the  greater  would  be  the  difl'ercnce  between  this  and  the 
temperature  of  the  animal,  until  finally  the  latter  would  rise  to  such 
a  height  that  the  animal  would  die  of  heat-stroke,  its  tissues  being 
destroyed  by  the  actual  temperature  attained.  A  certain  protection 
is  afforded  to  most  cold-blooded  terrestrial  animals  by  the  fact 
that  their  surface  is  moist,  and  that  with  a  rise  of  external  tempera- 


30' 


40 


O  10"  20' 

^    *  Externa/  temp.  C° 

Fio.  542.     Effect  of  alterations  in  the  temperature  of  the  surrounding  medium 
on  output  of  COg  in  cold-blooded  (poikilothermic)  animals.     (C.  J.  Maktin.) 


ture  the  rate  of  evaporation  on  the  surface  increases,  so  that  the 
increase  in  the  rate  of  cooling  by  evaporation  more  than  corresponds 
to  the  rate  of  increase  in  the  heat  production,  which  would  tend 
to  raise  the  body  temperature.  Most  of  these  animals,  how- 
ever, escape  from  any  extreme  rise  of  external  temperature  by 
burrowing  underground  or  taking  to  the  water,  while  in  plants  a 
rise  of  external  temperature  assists  transpiration  to  such  an  extent 
that  the  temperature  of  the  plant  is  generally  several  degrees  below 
that  of  the  surrounding  atmosphere.  The  extreme  variability 
in  the  metabolism  of  such  animals  implies  a  state  of  dependence  of 
all  the  activities  of  the  body  on  the  environment,  which  would  pre- 
vent the  utilisation  to  the  full  of  the  available  sources  of  energy. 
An  animal  whose  metabolism  was  more  or  less  independent  of  the 
surrounding   temperature    must    have   a   great  advantage    over   an 


1308  PHYSIOLOGY 

animal  liable  to  have  his  activities  reduced  and  paralysed  by  a  sudden 
spell  of  cold  weather  ;  this  greater  independence  of  the  environment 
which  is  characteristic  of  elevation  of  type,  has  been  achieved  by  the 
warm-blooded  animals,  including  man.  Such  animals  are  often 
spoken  of  as  Jiomoiothermic,  i.e.  animals  possessing  a  uniform  tempera- 
ture, in  contradistinction  to  the  cold-blooded  animals,  which  are 
foihiloihermic  and  possess  a  temperature  varying  with  that  of  their 
surroundings. 

Amongst  the  warm-blooded  animals  the  body  temperature  may 
be  very  different  according  to  the  species.  In  birds  it  is  generally 
from  39°  to  40°  C.  ;  in  mammals  it  varies  from  35°  to  40°  0.  The 
temperature  of  man  varies  within  slight  limits  about  37°C.  (98-4°  F.). 

THE  DIURNAL  VARIATIONS  IN  THE  BODY  TEMPERATURE 
In  any  animal  the  seat  of  heat  production,  e.g.  a  contracting 
muscle,  must  be  warmer  than  an  inactive  tissue,  and  this  again  than 
a  tissue  from  which  heat  is  being  rapidly  abstracted,  such  as  the  skin. 
Owing,  however,  to  the  rapidity  of  the  circulation  of  the  blood,  the 
temperature  of  the  internal  organs  can  be  regarded  as  approximately 
uniform.  The  temperature  of  man  is  usually  taken  in  the  mouth, 
rectum,  or  axilla.  In  the  case  of  the  mouth  the  temperature  is 
liable  to  fluctuation  with  the  rate  of  breathing,  the  mouth  being  cooled 
by  the  passage  of  the  air  through  the  nasal  cavities.  There  is  also 
probably  loss  of  heat  through  the  cheeks.  In  order  to  determine  the 
temperature  in  this  situation  the  mouth  should  be  kept  closed  for  a 
few  minutes  and  then  the  bulb  of  the  thermometer  inserted  under  the 
tongue,  and  the  lips  kept  closed  on  the  stem  of  the  thermometer  for 
five  minutes.  Except  in  cases  where  the  cutaneous  vessels  are  much 
dilated,  the  temperature  of  a  thermometer  in  the  axilla  takes  a  con- 
siderable time  to  rise  to  that  of  a  thermometer  in  the  mouth  ;  it 
should  never  be  left  less  than  ten  minutes  in  this  situation.  The  follow- 
ing Table  represents  the  temperature  of  different  parts  of  the  body  : 

Surface 

Skin  covered  with  clothes 33°  to  35°  C. 

Naked  skin  in  bath  at  5°  C 17°  C. 

»         ,,         »            25°  C 26-5°  C. 

Muscles  12  mm.  below  the  Surface 

In  bath  at  5°  C 36-3°  C. 

„     „      25°C 36-9°  C. 

The  body  temperature  of  man  shows  variations  of  several  tenths  of 
a  degree  according  to  the  time  of  ,day  at  which  the  temperature  is 
taken.  The  highest  temperature  is  obtained  about  six  or  seven  in 
the  evening,  and  the  lowest  at  about  four  or  five  o'clock  in  the  morning. 


THE  TEMPERATURE  OF  THE  BODY  1309 

With  these  diurnal  changes  in  temperature  are  associated  parallel 
oscillations  in  the  rate  of  metabolism  as  shown  by  the  elimination  of 
carbon  dioxide.  They  are  probably  determined  by  the  changes  in  the 
movement  and  tension  of  the  muscles  occurring  during  the  waking 
hours.  If  the  habits  of  a  man  or  animal  be  reversed,  so  that  he 
sleeps  in  the  daytime  and  performs  his  normal  vocation  by  night,  it 
is  possible  to  reverse  also  the  direction  of  the  diurnal  variations  in 
temperature.  The  temperature  may  be  also  affected  temporarily 
by  various  acts,  such  as  taking  of  food,  or  the  muscular  work  ;  the 
influence  of  the  latter  factor  is  often  very  marked.  In  many  individuals 
a  hard  game  at  tennis  suffices  to  raise  the  temperature  to  39'^  C. 
(100°  F.),  and  even  the  healthiest  individual  will  show  some  change  in 
his  temperature  as  the  result  of  exercise.  Pembrey  found  that  the 
act  of  marching,  especially  in  the  ill-adapted  clothes  of  the  British 
soldier,  led  to  a  considerable  rise  in  temperature,  a  rise  which  is 
apparently  responsible  for  the  discomfort  and  fatigue  observed  under 
such  circumstances.  Such  a  change  in  the  body  temperature  is  merely 
temporary  in  its  effects,  and  insignificant  in  comparison  with  the 
wonderful  uniformity  of  temperature  observed  in  men  of  all  races  and 
of  all  climes  under  most  varying  conditions  of  food  and  activity. 

Just  as  there  are  limits  to  the  power  of  the  organism  to  regulate 
its  temperature  when  there  is  an  excessive  formation  of  heat  in  the  body, 
so  there  are  limits  to  the  regulation  of  temperature  to  severe  altera- 
tions in  the  temperature  of  the  external  medium.  Thus  if  the  body  is 
subjected  to  excessive  external  cold,  or  the  loss  of  heat  be  increased 
by  absence  of  clothes,  by  depriving  an  animal  of  its  fur,  or  by  immer- 
sion in  a  cold  bath,  the  temperature  of  the  body  may  sink  continuouslv. 
This  fall  of  temperature  in  the  higher  animals  is  very  soon  followed  by 
paralysis  of  the  highest  nerve-centres  and  loss  of  consciousness.  The 
centres  in  the  medulla  are  later  on  affected,  so  that  the  respiration  is 
slowed  and  the  blood  pressure  falls.  If  the  temperature  does  not 
fall  too  low  it  is  possible  to  revive  the  animal  or  man  by  checking  the 
loss  of  heat  or  by  supplying  artificial  warmth.  Recovery  has  in  fact 
been  observed  in  men  in  whom,  as  a  result  of  exposure,  the  body 
temperature  had  fallen  to  24°  C.  In  the  same  way  exposure  to  extreme 
heat,  especially  associated  with  muscular  exercise  and  increased 
production  of  heat  in  the  body,  may  cause  a  rise  of  the  body  tempera- 
ture. A  man,  or  animal,  whose  temperature  is  raised  above  the  normal, 
is  said  to  be  in  a.  state  of  pyrexia.  A  rise  of  2°  or  3°  C.  is  associated 
with  all  the  phenomena  which  characterise  fever,  i.e.  quickening  of 
pulse  and  respiration,  malaise,  headache,  and  loss  of  muscular  power. 
If!  the  temperature  rise  to  a  greater  degree  than  this  the  patient 
mav  lose  consciousness,  and  death  ensues  at  a  temperature  of  about 
44°  C. 


1310  PHYSIOLOGY 

The  very  small  variations  presented  by  the  body  temperature  in 
mammals,  even  under  the  influence  of  considerable  variation  in 
external  temperature,  or  in  the  production  of  heat  in  the  body,  connotes 
an  accurate  adaptation  between  the  production  of  heat  in  the  body 
and  the  loss  of  heat  from  the  body.  The  regulation  of  the  temperature 
can  be  effected  either  by  regulation  of  heat  production,  by  alteration 
in  the  rate  of  loss  of  heat,  or  by  a  combination  of  both  mechanisms.  It 
will  be  convenient  to  deal  with  these  two  methods  of  regulation  under 
separate  headings. 

THE  PRODUCTION  OF  HEAT  IN  THE  BODY 

The  reactions  mainly  responsible  for  heat  production  in  the  body 
are  those  associated  with  oxidation  ;  the  processes  of  disintegration, 
such  as  are  effected  by  means  of  hydrolytic  ferments,  accounting  for 
a  very  small  part  of  the  heat  evolved. 

In  these  processes  of  oxidation  all  the  organs  participate,  the 
most  important,  especially  in  relation  to  the  regulation  of  heat  pro- 
duction, being  the  skeletal  muscles.  These  represent  more  than 
half  of  the  total  weight  of  the  soft  tissues  of  the  body,  and  even  during 
rest  are  the  seat  of  oxidative  processes  and  therefore  of  heat  forma- 
tion. Heat  formation  varies  with  the  state  of  tone  of  the  muscles, 
and  is  largely  increased  with  every  active  contraction.  The  effect  of 
muscular  activity  on  the  total  output  of  energy  of  the  body  is  well 
represented  in  the  Table  given  on  p.  715. 

It  is  probable  that,  in  relation  to  their  size  at  any  rate,  the  glands 
are  still  more  effective  as  heat  producers.  The  liver,  and  the  blood 
flowing  from  the  liver,  have  been  stated  to  present  a  higher  tempera- 
ture than  any  other  part  of  the  body.  On  the  other  hand,  the  nervous 
system,  although  dependent  on  a  constant  supply  of  oxygen  for  its 
activities,  does  not  appear  to  be  the  seat  of  extensive  metabolic 
changes,  nor  does  the  heat  produced  in  this  system  play  any  great  part 
in  maintaining  the  temperature  of  the  body. 

The  skeletal  muscles  are  controlled  by  the  central  nervous  system  ; 
if  separated  from  their  centres  in  the  cord  they  become  flaccid  and 
rapidly  atrophy.  The  heat  production  in  the  muscles  is  therefore 
also  dependent  on  their  connection  with  the  central  nervous  system. 
If  this  connection  be  severed  either  by  curare  or  section  of  the  cord,  or 
if  the  reflex  play  of  impulses  on  the  muscles  be  abolished  by  anaes- 
thetics, the  animal  will  react  like  a  cold-blooded  animal.  The  total 
metabolism  of  the  body  and  the  total  production  of  heat  sink  to  a 
minimum,  and  are  diminished  by  application  of  cold,  or  increased  by 
application  of  warmth,  to  the  surface  of  the  body.  On  the  other  hand, 
in  the  intact  animal  changes  of  temperature  in  the  environment  pro- 
voke, reflexly  by  their  action  on  the  muscles,  changes  in  the  opposite 


THE  TEMPERATURE  OF  THE  BODY 


l.-Jll 


direction.     Thus  exposure  to  cold  increases  and  to  heat  diminishes 
muscular  metabolism  and  the  heat  production  of  the  body. 

The  effects  of  variations  in  the  external  temperature  on  the  meta- 
bolism of  warm-blooded  animals  are  well  shown  in  the  experiment, 
from  which  the  following  Tables  are  taken,  on  the  COg  output  in  the 
ornithorhynchus  and  in  the  rabbit  (Martin) : 


1.  Orxithorhyxchi-s.     Weight,  093  grm. 

;    Surface,  876 

SQ.    CENTIMS. 

Temperature     \ 
of              1 
environment 

Temperature 

of 

animal 

Difference  in 
temperature, 
animal  and 
environment 

COo  per  hour, 
in  grammes 

COj  per  hour 

per  1000 
sq.  centims., 
in  grammes 

5 

31-8 

26-8 

1-090 

1-244 

10 

320 

220 

•722 

•825 

20 

32-6 

12-6 

•405 

-463 

32 

33-6 

1-6 

•336 

•383 

35 

35-3 

•3 

•377 

•430 

2.  Rabbit.     Weight,  750  grm. 


Temperature 

of 
environment 


Temperature 

of 

animal 


Difference  in 
temperature, 
animal  and 
environment 


CO2  per  hour, 
in  grammes 


CO-2  per  hour 

per  1000 
sq.  centims., 
in  grammes 


10 
20 
35 
40 


37-5 
38-0 
38^7 
405 
41-6 


32^5 

280 

18^7 

5^5 


1^426 

1038 

•912 

•766 


1-543 

1-124 

•987 

•829 

•971 


In  the  former  animal,  where  the  regulation  of  the  temperature  of 
the  body  is  effected  almost  entirely  by  changes  in  heat  production,  the 
effect  of  warming  the  environment  of  the  animal  on  the  CO.,  output 
is  extremely  marked.  It  will  be  noticed  that  the  CO2  per  hour  sinks 
continuously  with  rising  temperature  up  to  32°  C.  When  the  tempera- 
ture of  the  chamber  was  raised  to  3-5''  the  temperature  of  the  animal  rose 
considerably,  i.e.  the  regulatory  mechanism  was  failing,  so  that  the 
same  effect  was  produced  on  metabolism  as  is  observed  in  working  with 
cold-blooded  animals.  The  same  change,  though  less  marked,  is 
observed  on  exposing  the  rabbit  to  a  gradual  rising  temperature. 
Here,  however,  the  process  of  regulation  is  aided  by  alterations 
in  the  heat  lost  as  well  as  in  the  heat  production  (Fig.  .^43).  If  the 
animals  be  observed,  whilst  subjected  to  changes  of  temperature, 
it  will  be  evident  to  any  one  that  the  regulation  is  associated  with 
changes  in  muscular  activity.    At  30°  to  35°  C.  the  animals  will  lie 


1312 


PHYSIOLOGY 


perfectly  flaccid,  breathing  rapidly,  or  may  go  to  sleep.  On  cooling 
they  at  once  become  more  vigorous  and  perform  active  move- 
ments in  their  cage.  The  same  effects  of  changes  in  the  external 
temperature  are  familiar  in  ourselves.  The  slackness  and  extreme 
disinclination  to  violent  exercise  observed  in  hot  moist  weather,  con- 
trasted with  the  stringing  up  of  the  tone  of  the  muscles  which  follows 
exposure  to  cold,  and  which  may  be  associated  with  voluntary  exercise 


£-0 


10°  £0°  30 

* *-  Eocb!^   Cemp.  de^.  CenC. 

Fig.  543.     Effect  of  variations  in  the  external  temperature  on  the  CO.,  output 
(per  1000  cm.2  body  surface)  of  warm-blooded  animals.     (C.  J.  Martin.) 


to  keep  ourselves  warm,  are  indications  of  the  important  part  played 
by  the  muscles  in  determining  the  heat  production  of  the  body.  As 
a  rule  the  immersion  of  a  man  in  a  cold  bath  for  a  minute  or  two 
increases  considerably  his  output  of  COg.  It  is  possible,  however, 
to  sit  in  a  bath  and  by  an  act  of  the  will  keep  all  the  muscles  in  a  state 
of  relaxation.  Under  these  circumstances  the  temperature  of  the 
body  rapidly  falls,  and  with  it  the  rate  of  metabolism,  as  judged 
by  the  output  of  carbon  dioxide. 

This  process  of  adjustment  of  the  body  temperature  by  variations 
in  the  heat  production,  so  long  as  it  represents  the  only  method,  is 
extravagant  of  energy  directly  the  difference  in  temperature  between 


THE  TEMPERATURE  OF  THE  BODY  1:313 

animal  and.  environment  attains  any  considerable  degree.  In  the 
very  perfect  adjustment  of  the  temperature  which  is  present  in  the 
higher  mammals,  regulation  of  the  heat  loss  plays  a  greater  part  than 
regulation  of  heat  production.  The  economy  of  adjustment  by  heat 
loss  is  well  shown  if  we  compare  in  echidna  and  rabbit  respectively 
the  percentage  alteration  in  COg  production  when  the  difference  in 
temperature  between  animal  and  environment  varies  from  10°  C. 
to  20°  C.  This  is  for  echidna  72  per  cent.,  for  mammals  16  per  cent. 
In  echidna  variations  in  heat  loss  can  be  practically  neglected,  so 
that  the  whole  of  the  work  of  regulating  the  body  temperature  falls 
on  the  heat  production.  As  soon  as  the  external  temperature  falls 
below  a  certain  degree  the  mechanism  fails,  the  animal's  temperature 
falls,  and  it  passes  into  a  state  of  hibernation. 

THE  REGULATION  OF  HEAT  LOSS 
In  all  temperate  climates,  and  in  fact  in  all  climates  except  under 
certain  exceptional  conditions,  the  temperature  of  the  warm-blooded 
animal  is  higher  than  that  of  his  environment,  so  that  there  must  be  a 
constant  loss  of  heat  from  the  surface  of  the  body.  In  the  warm- 
blooded animals  in  the  arctic  regions,  and  in  those  which  have  adopted 
an  aquatic  existence,  the  thick  layer  of  fat  which  underlies  the  sldn 
protects  the  active  portions  of  the  body,  the  muscles  and  internal 
organs,  from  excessive  loss  of  heat  to  the  surrounding  medium.  In 
most  terrestrial  animals  the  loss  of  heat  is  also  diminished  by  fur  and 
feathers  with  which  these  animals  are  clothed,  and  in  ourselves  the 
same  office  is  performed  by  clothes,  which  are  capable  of  volimtary 
graduation  to  external  conditions.  The  value  of  these  different 
coverings  depends  on  the  fact  that  air  is  a  very  bad  conductor  of  heat. 
In  the  case  of  a  naked  man  the  layer  of  air  immediately  in  contact 
with  the  surface  of  the  body  is  warmed,  becomes  lighter,  and  rises,  its 
place  being  taken  by  fresh  cold  air.  Loss  of  heat  is  increased  by  a 
draught,  which  quickens  the  rate  at  which  the  layers  of  air  in  contact 
with  the  surface  are  renewed.  In  the  case  of  clothes  the  material 
encloses  layers  of  air  and  hinders  it  from  free  circulation,  and  it  is  the 
air  enclosed  in  the  meshes  of  the  garments  and  between  the  different 
layers  of  garments  that  plays  the  greater  part  in  preventing  loss  of 
heat.  The  rapid  cooling  effect  of  wet  clothes  is  partly  due  to  the  replace- 
ment of  layers  of  air  by  water,  which  is  a  much  better  conducting  fluid. 
In  addition  to  the  loss  of  heat  by  convection,  i.e.  by  warming  the 
layers  of  air  in  contact  with  the  body,  heat  is  also  lost  by  radiation,  i.e. 
by  an  exchange  of  heat  between  the  surface  of  the  body  and  that  of 
surrounding  cooler  objects.  This  loss  is  also  prevented  by  clothing. 
Since  the  material  of  which  clothes  are  made  does  not  allow  the  passage 
of  radiant  heat,  they  absorb  the  heat  leaving  the  body  and  become 

83 


1314  PHYSIOLOGY 

warm.  This  warm  article  of  clothing  may  in  its  turn  act  as  a  centre 
for  the  loss  of  radiant  heat,  which  may  again  be  prevented  by  putting 
on  another  layer.  It  is  a  familiar  experience  that  a  multiplication  of 
garments  is  more  effective  in  retaining  the  heat  of  the  body  than 
merely  increasing  the  thickness  of  the  individual  garments.  The  rate 
of  loss  of  heat  by  radiation  is  diminished  by  a  rise  of  the  amount  of 
watery  vapour  in  the  air,  since  this  makes  the  air  more  opaque  to 
the  passage  of  radiant  energy.  Since  the  loss  of  heat  depends  on  the 
difference  of  temperature  between  the  surface  of  the  body  and  the 
surrounding  air,  or  objects,  it  will  be  largely  affected  by  the  temperature 
of  the  skin,  and  therefore  by  the  amount  of  blood  flowing  through  the 
skin.  The  blood-flow  through  the  skin  is  under  the  control  of  the  central 
nervous  system,  through  the  vaso-motor  and  vaso-dilator  nerves, 
and  it  is  by  altering  the  size  of  these  vessels  that  the  central  nervous 
system  chiefly  acts  in  regulating  heat  loss.  In  cold  weather,  or  when 
the  heat  production  in  the  body  is  low,  the  vessels  are  constricted,  the 
skin  is  cold,  and  the  heat  loss  is  small.  On  the  other  hand,  if  the 
temperature  of  the  surrounding  air  is  high,  or  a  large  amount  of  heat  is 
being  produced  in  consecjuence  of  muscular  exercise,  the  vessels  are 
dilated  and  the  skin  is  hot.  In  hot  weather  the  dilatation  in  the 
cutaneous  vessels  is  associated  with  muscular  inactivity,  so  that 
there  is  a  derivation  from  the  muscles,  where  the  blood  is  not  required, 
to  the  skin,  where  a  considerable  circulation  is  necessary. 

Loss  of  heat  by  radiation  and  convection  can  only  happen  when 
the  temperature  of  the  surrounding  air  is  lower  than  that  of  the  body. 
The  body  temperature  can,  however,  be  maintained  at  its  normal 
height  in  an  atmosphere  with  a  temperature  much  higher  than  37-5°  C, 
and  this  in  spite  of  the  fact  that  the  production  of  heat  in  the  body  is 
still  going  on.  In  this  case  there  is  a  profuse  secretion  of  sweat  on 
the  surface  of  the  body.  In  the  evaporation  of  the  sweat,  especially 
if  aided  by  a  draught  of  air,  a  large  amount  of  heat  becomes  latent 
and  is  abstracted  from  the  body,  which  is  therefore  kept  at  a  tempera- 
ture below  that  of  the  surrounding  atmosphere.  If  the  secretion  of 
sweat  is  checked,  by  depriving  an  animal  or  man  of  water,  or  if  its 
evaporation  be  impeded  by  placing  him  in  an  atmosphere  already 
saturated  with  aqueous  vapour,  the  temperature  of  the  body  runs  up 
rapidly  and  death  ensues  from  hyperpyrexia,  or  heat-stroke.  Although 
a  man  can  stand  exposure  to  a  temperature  of  200°  or  even  250°  F.  for 
a  considerable  time  provided  that  the  air  is  dry,  a  temperature  of 
89°  F.  is  rapidly  fatal  if  the  air  be  saturated  with  moisture.  The  same 
mechanism  comes  into  play  when  the  heat  production  in  the  body 
is  very  largely  increased,  as  by  violent  exercise.  Under  these  con- 
ditions a  man  may  sweat  profusely  when  the  temperature  of  the 
surrounding  atmosphere  is  at  0°  C. 


THE  TEMPERATURE  OF  THE  BODY  1315 

The  main  regulation  of  heat  loss  thus  takes  place  by  the  control  of 
the  nervous  system  over  the  cutaneous  circulation  and  the  sweat- 
glands.  Besides  these  channels  of  heat  loss,  others  may  play  an 
important  part  under  certain  conditions.  Heat  is  lost  to  the  body  in 
warming  the  food  and  air  which  are  taken  in.  It  is  also  lost  in  respira- 
tion in  the  evaporation  of  water  and  the  setting  free  of  CO2  from 
watery  solution  into  the  expired  air.  The  following  estimate,  by 
Tigerstedt,  represents  the  proportion  of  losses  in  an  adult  man  by 
these  dilferent  ways  : 

A.    Warmtno  the  Food  and  Air 

(1)  1500  g.  water  drunk   at  15°  C.  and  warmed  to  37-5°— raised  Cal. 

therefore  22-5° =      33-76 

(2)  1500  g.  food  eaten  at  25°  C.  (mean)  and  warmed  to  37-5° — raised 

therefore  12-5  ;  specific  heat  0-8  .....      =     15-00 

(3)  15,000  g.  (=  11,500  1.)  air  respired  at  15°  C.  and  warmed  to  37-5° 

—raised  therefore  22-5°  ;  sijecific  heat  0-237  .  .  .      =     79-95 


128-70 


B.     Loss  OF  Water  and  CO,  in  the  Breath 


(4)  It  is  assumed  that  the  inspired  air  is  half  saturated  with  watery 

vapour  at  15°  C.  and  that  the  expired  air  is  fully  satiirated  at 
37-5°  C.  Approximately  450  g.  of  water  would  be  given  off 
therefore  in  the  form  of  vapour  from  the  respiratory  passages  ; 
the  latent  heat  of  the  water  vapour  is  0-537  Cal.  .  .      =    241  "70 

(5)  The  absorption  of  heat  in  the  liberation  of  CO2  from  the  lungs 

(800  g.);  0-134  Cal.  per  g.  .  .         ."       .         .         .     =    107-20 


348-90 
From  above 128-70 


Total 477-GO 

The  sum  of  heat  losses  specified  under  these  five  headings  amounts 
to  477-60  Cal.  Estimating  the  total  heat  loss  of  an  adult  man  at 
2400  Cal.,  this  sum  represents  only  about  20  per  cent,  of  the 
total.  The  remaining  80  per  cent,  (in  round  numbers)  takes  place 
through  the  skin. 

If  we  estimate  the  total  heat  loss  of  an  adult  man  at  2400  calories, 
we  may  say  that  about  5  per  cent,  of  the  total  heat  loss  takes  place 
by  warming  the  food  and  air,  about  15  per  cent,  by  the  evaporation  of 
water  and  CO2  in  respiration,  and  about  80  per  cent,  by  radiation 
and  convection  and  the  evaporation  of  sweat  from  the  skin.  The  pro- 
portion represented  by  the  last  factor  will  increase  very  largely  in  the 
presence  of  a  high  external  temperature,  or  of  an  excessive  heat  pro- 
duction in  consequence  of  violent  muscular  exercise. 


1316  PHYSIOLOGY 

THE  NERVOUS  MECHANISM  FOR  HEAT  REGULATION 
The  accurate  balance  between  heat  production  and  heat  loss 
which  is  responsible  for  the  nearly  constant  temperature  of  man, 
indicates  the  active  co-operation  of  the  central  nervous  system 
in  every  step  of  the  process.  Whether  this  function  of  tempera- 
ture regulation  can  be  specially  localised  at  any  part  of  the 
central  nervous  system,  so  that  it  would  be  possible  to  speak  of  a 
heat-centre  in  the  same  way  as  we  speak  of  a  respiratory  or  vaso- 
motor centre,  is  doubtful.  Many  observers  have  found  that  injury 
to  the  corpus  striatum  causes  a  rise  of  temperature  associated  with 
increase  both  in  heat  production  and  in  heat  loss.  On  the  other 
hand,  injury  to  or  pathological  lesions  of  the  pons  Varolii  often 
lead  to  an  increased  production  of  heat  in  the  body,  which  is  not 
compensated  for  sufl&ciently  by  heat  loss,  and  so  causes  death  by 
hyperpyrexia.  It  has  been  suggested  that  the  thermogenic  centre, 
i.e.  that  responsible  for  regulating  heat  produxition,  is  situated  at  a 
lower  level  in  the  nervous  system  than  the  thermotaxic  system,  i.e.  that 
which  presides  over  and  determines  the  balance  between  heat  pro- 
duction and  heat  loss.  The  centres  for  heat  loss  must  be  placed 
in  the  medulla,  at  any  rate  so  far  as  concerns  control  of  heat  loss  by 
alterations  in  the  blood-supply  to  the  skin  or  in  the  secretion  of  sweat. 
The  facts  at  our  disposal  are,  however,  too  meagre  to  warrant  any 
definite  localisation  of  the  heat-regulating  function  in  the  central 
nervous  system,  or  any  such  accurate  analysis  of  the  regulating 
function  as  has  been  just  suggested. 

In  many  warm-blooded  animals  the  abiUty  to  maintain  a  con- 
stant temperature  is  not  fully  developed  until  some  time  after  birth. 
Pembrey  has  shown  that  in  the  guinea-pig  and  chick,  in  which  the 
nervous  system  is  fully  functional  at  birth,  the  heat-regulating 
mechanism  is  also  completely  adequate,  whereas  animals  such  as  rats, 
pigeons,  or  the  human  child,  which  are  born  in  a  helpless  condition,  only 
acquire  the  power  of  regulating  their  own  temperature  some  time  after 
birth.  As  we  should  expect,  the  development  of  the  power  of  regu- 
lating heat  production  runs  pari  passu  with  the  acquisition  of  control 
by  the  nervous  system  over  the  muscles  of  the  body. 


/ 


CHAPTER  XX 
THE  DUCTLESS  GLANDS 

INTERNAL   SECRETIONS 

In  unicellular  organisms,  as  in  the  rest  of  the  living  world,  activity 
consists  in  adaptation  to  external  conditions.  The  changes  in  the 
environment  which  determine  the  reactions  of  these  organisms  may 
occur  at  their  surface  or  at  some  distance.  Among  the  stimuli  which, 
acting  from  a  distance,  evoke  the  reaction  of  unicellular  organisms, 
probably  the  most  important  are  those  accompanied  by  chemical 
changes.  The  interrelation  of  micro-organisms  with  one  another  is 
determined  almost  entirely  by  such  chemical  stimuli.  Thus  the 
antherozoids  of  ferns  are  attracted  to  the  ovule  in  consequence  of  the 
production  in  the  tissue  surrounding  the  latter  of  substances  such  as 
malic  acid.  Among  micro-organisms  we  find  some  which  leave  places 
rich  in  oxygen,  while  others  move  towards  any  spot  in  their  environ- 
ment where  oxygen  is  most  plentiful.  These  reactions  of  unicellular 
organisms  to  chemical  stimuli  are  classed  together  under  the  term 
chemiotaxis.  When  the  cells  are  united  together  to  form  cell 
colonies,  or  when,  as  in  the  metazoa,  the  multicellular  aggregate  is 
formed  by  the  failure  of  the  products  of  division  of  the  ovum  to 
separate  one  from  another,  the  interrelations  between  the  different 
cells  forming  the  organism  are  still  largely  determined  by  chemical 
stimuli.  In  fact,  in  the  lowest  metazoa,  such  as  the  sponge,  we 
know  of  no  other  means  of  correlating  the  reactions  of  different  parts 
of  the  cell  aggregate.  If  a  foreign  substance  be  introduced  into  the 
living  tissue  of  a  sponge  it  becomes  speedily  surrounded  with  a  collec- 
tion of  wandering  phagocytic  cells,  called  from  the  surrounding  parts 
by  the  diffusion  of  chemical  substances  from  the  seat  of  the  lesion 
into  the  fluids  of  the  body.  The  same  chemical  sensibility  determines 
the  aggregation  of  leucocytes  around  bacteria  or  dead  tissue,  which 
forms  the  essential  feature  of  the  process  of  inflammation  in  higher 
animals. 

When  the  reaction  of  distant  parts  of  the  body  to  a  change  occurring 
in  any  one  part  depends  on  the  diffusion  of  some  substance  from  a 
stimulated  part,  the  total  reaction  must  require  a  considerable  time 
for  its  full  development.  A  much  more  effective  method  of  correla- 
tion was  acquired  by  the  evolution  of  a  nervous  system,  by  means  of 

1317 


1318  PHYSIOLOGY 

which  the  consensus  partium  could  be  maintained  by  the  rapid  propa- 
gation of  molecular  changes  along  differentiated  paths  in  the  proto- 
plasm. The  development  of  this  second  mode  of  correlation  of 
activities  did  not,  however,  do  away  with  the  necessity  for  the  more 
primitive  method.  Even  in  the  higher  animals,  where  rapidity  of 
reaction  is  not  required,  we  find  adaptations  carried  out  in  response 
to  some  change  in  distant  parts  of  the  body,  the  message  having  been 
chemical  and  not  nervous  in  character  {e.g.  the  secretin  mechanism 
for  pancreatic  secretion). 

When  we  speak  of  the  chemical  correlation  of  the  activities  of 
the  different  parts  of  the  body,  it  is  important  not  to  confuse 
processes  which  have  little  or  nothing  in  common.  In  one  sense 
we  may  say  that  every  cell  in  the  body  is  chemically  connected 
with  and  dependent  on  all  the  other  cells  in  the  body.  This  inter- 
dependence is  a  necessary  consequence  of  the  differentiation  of  func- 
tion associated  with  increased  complexity  of  the  organism.  Thus 
the  food-stuffs  are  digested  and  absorbed  by  the  cells  lining  the 
alimentary  canal  and  are  then  transmitted,  more  or  less  changed 
by  these  cells,  to  all  the  other  tissues  of  the  body.  The  liver  stores 
up  glycogen  and  is  ready  to  give  of  its  store  to  any  tissue  in  need  of 
carbohydrate.  All  the  tissues  probably  produce  urea,  which  passes 
to  the  kidneys  and  there  excites  the  act  of  excretion.  All  tissues 
produce  carbon  dioxide,  which  passes  to  the  lungs  to  be  excreted, 
but  as  it  traverses  the  respiratory  centre  it  arouses  respiratory  move- 
ments which  are  exactly  proportioned  to  the  tension  of  the  carbon 
dioxide  and  therefore  to  the  need  of  the  whole  body  to  eliminate  this 
waste  product.  The  liver  receives  ammonia  from  the  alimentary 
canal  and  converts  it  into  urea,  thus  shielding  all  the  other  tissues 
from  the  poisonous  effects  which  would  be  produced  by  the  entrance  of 
the  ammonia  into  the  general  circulation.  Thus  one  organ  may 
receive  and  modify  any  substance  or  food-stuff  so  as  to  prepare  it  for 
more  ready  assimilation  by  other  tissues.  It  may  shield  these  other 
tissues  from  the  poisonous  effects  of  certain  waste  products,  either  by 
converting  these  into  harmless  substances  or  by  excreting  them  from 
the  body.  In  all  these  cases  the  tissues  are  dealing  with  some  sub- 
stance which  is  utilised  in  bulk,  or  which,  by  its  accumulation,  could 
exert  a  toxic  influence  on  other  tissues.  We  are  probably  justified  in 
treating  apart  a  group  of  phenomena  in  which  the  substance  trans- 
mitted from  one  part  of  the  organism  to  another  is  significant  almost 
entirely  as  an  excitatory  agent,  and  has  little  or  no  value  as  a  source 
of  energy.  When  the  adaptation  to  a  change  at  a  consists  in  the 
activity  of  an  organ  b,  the  activity  of  b  can  be  evoked  either  by  a 
nerve  impulse  passing  from  a  to  the  central  nervous  system  and  from 
this  to  B,  or  by  the  production  at  a,  as  a  direct  consequence  of  the 


THE  DUCTLESS  GLANDS  L319 

stimulus,  of  a  specific  chemical  substance,  which  passes  into  the  cir- 
culating blood  to  B,  where  in  its  turn  it  will  excite  the  required  state 
of  action.  Such  chemical  messengers  are  designated  hormones,  from 
opfxati),  '  I  excite.'  We  have  already  met  with  several  examples 
of  such  bodies.  It  may  be  interesting  here  to  consider  what  must  be 
their  general  character  if  they  are  to  fulfil  the  part  of  chemical 
messengers. 

(1)  In  the  first  place,  they  must  not  be  antigens,  i.e.  their  injection 
into  the  blood-stream  must  not  evoke  the  production  of  an  anti-body. 
If  this  were  the  case,  the  hormone,  on  entering  the  blood-stream, 
would  meet  its  anti-body  and  would  be  unable  to  exert  any  effect 
on  the  appropriate  reacting  organ.  Practically  all  the  complex  colloid 
bodies  alhed  to  the  proteins,  e.g.  ferments,  egg  albumin,  peptone,  sera 
of  different  animals,  when  injected  into  the  blood-stream,  cause  the 
production  of  the  corresponding  anti-body.  The  hormones  must  be 
simpler  in  character  than  such  substances  and  probably  have  a  precise 
and  comparatively  simple  chemical  or  molecular  constitution. 

(2)  Since  they  must  be  carried  by  the  blood-stream  to  the  reacting 
organ  they  must  in  most  cases  be  susceptible  to  easy  passage  through 
the  walls  of  the  blood-vessels  if  they  are  to  excite  a  reaction  within  a 
fairly  short  space  of  time.  This  consideration  would  also  tend  to 
keep  their  molecular  weight  comparatively  low. 

(.3)  As  a  rule  the  chemical  messenger  must  excite  a  state  of  activity 
in  response  to  a  change  in  some  other  part  of  the  body.  When  the 
primary  change  passes  away,  the  action  of  the  hormone  should  also 
disappear.  On  this  account  it  is  necessary  that  the  hormone  should 
either  be  susceptible  of  easy  destruction,  by  oxidation  or  otherwise, 
in  the  fluids  of  the  body,  or  be  readily  excreted,  so  that  its  action  may 
not  be  continued  indefinitely. 

In  previous  chapters  we  have  already  come  across  several  examples 
of  correlated  activities  of  different  tissues  effected  by  chemical  means. 
It  is  perhaps  questionable  whether  we  should  regard  carbon  dioxide,  or 
the  lactic  acid  produced  by  a  contracting  muscle,  as  a  hormone  in  the 
strict  sense  of  the  term,  since  both  these  products  are  produced  in 
large  quantities  as  the  final  product  of  oxidation  or  disintegration  of 
the  food-stuffs.  Carbon  dioxide  is,  however,  rapidly  eliminated  from 
the  body,  and  lactic  acid  is  equally  rapidly  oxidised  in  the  body,  and 
there  is  no  doubt  that  the  activity  of  the  respiratory  centre  is  deter- 
mined by  the  presence  of  this  substance  in  the  blood  and  is  thereby 
perfectly  co-ordinated  with  the  activities  of  the  whole  of  the  rest  of 
the  organism.  In  the  alimentary  canal  the  secretion  of  pancreatic 
juice  at  the  precise  moment  when  it  is  required  in  the  duodenum  for  the 
digestion  of  the  food  arriving  there  from  the  stomach  is  evoked  by  the 
production  in  the  cells  of  the  intestinal  mucous  membrane  under  the 


1320  PHYSIOLOGY 

agency  of  the  acid  of  the  gastric  juice  (the  specific  stimulus)  of 
a  substance  secretin.  This  substance,  which  is  heat  stable  and 
diffusible,  but  is  easily  destroyed  by  oxidation,  is  absorbed  into  the 
blood  and  carried  to  the  pancreas,  where  it  acts  as  a  specific  stimulus 
for  the  secretory  cells.  The  same  substance  excites  also  the  secretion 
of  bile  by  the  liver-cells  and  the  secretion  of  intestinal  juice  by  the 
glands  of  the  small  intestine.  These  are  perhaps  the  two  best  examples 
of  chemical  reflexes,  i.e.  adaptations  effected  by  chemical  means  rather 
than  by  impulses  passing  along  the  nerve-channels.  There  are, 
however,  many  other  examples  of  a  chemical  influence  exerted  by  one 
organ  on  another,  in  which  the  interaction  probably  depends  on  the 
production  of  minute  quantities  of  some  substance  acting  in  virtue  of  its 
excitatory  qualities  rather  than  of  its  value  as  a  source  of  energy.  For 
many  of  the  organs  of  the  body  we  know,  in  fact,  no  other  function 
than  the  production  of  some  substance  the  presence  of  which  in  the 
blood  is  a  necessary  condition  for  the  carrying  out  of  the  normal 
functions  either  of  growth  or  activity  of  many  other  parts  of  the  body. 
In  other  cases  an  organ  may  have  a  twofold  function.  Thus  the 
pancreas  gives  an  external  secretion  which  is  used  for  the  prepara- 
tion of  the  food  for  absorption,  and  an  internal  secretion  which, 
passing  into  the  blood,  exercises  an  important  influence  on  the  meta- 
bolism of  the  food-stuffs  after  absorption.  Other  instances  of 
these  chemical  correlations  may  be  cited.  The  secretion  of  gastric 
juice,  which  results  from  the  presence  of  peptones  or  other  substances 
in  the  stomach,  has  been  ascribed  by  Edkins  to  the  production  in  the 
pyloric  mucous  membrane  of  a  gastric  hormone,  which  travels  by  the 
blood  to  the  glands  of  the  fundus,  where  it  excites  secretion  of  gastric 
juice.  According  to  Frouin  the  injection  of  boiled  succus  entericus, 
free  from  secretin,  provokes  the  secretion  of  intestinal  juice.  In  the 
reproductive  system  we  have  many  examples  of  such  chemical  correla- 
tions. The  pancreas,  by  its  internal  secretion,  probably  influences 
not  only  the  oxidation  of  the  carbohydrates  but  also  the  assimilation 
of  the  food-stuffs  by  all  parts  of  the  small  intestine.  All  these  examples 
are  discussed  in  fuller  detail  in  other  parts  of  this  book.  There  is  one 
class  of  organs  in  which  a  chemical  influence  exerted  on  the  rest  of  the 
body  is  the  only  function  with  which  we  are  acquainted.  These  are 
included  under  the  term  ductless  glands.  As  examples,  we  may  cite 
the  suprarenal  bodies,  the  thyroid  and  parathyroids,  the  thymus  and 
the  pituitary  body. 

THE  SUPRARENAL  BODIES 
The  suprarenal  capsules  in  n^ammals  are  two  small  masses  lying 
on  the  upper  or  oral  side  of  the  kidneys.     They  consist  of  two  parts, 
the  cortex  and  the  medulla.      The    cortex    is    composed    of    cells 


THE  DUCTLESS  GLANDS  1321 

arranged  in  columns  or  in  a  reticular  fashion.  The  outermost  layer  of 
cells  often  presents  an  alveolar  structure,  the  lumen,  however,  being 
but  little  marked.  According  to  the  arrangement  of  the  cells  the 
cortex  is  divided  into  three  zones,  the  zona  glomerulosa,  zona  fascicu- 
lata,  and  zona  reticulata.  The  cells  themselves  are  distinguished  by 
the  large  amount  of  granules  they  contain,  which  give  the  ordinary 
reactions  for  fat,  but  consist  probably  of  lecithin  compounds.  In  some 
animals,  e.g.  the  guinea-pig,  the  cells,  especially  towards  the  inner  part 
of  the  gland,  contain  many  yellow  pigment  granules.  The  medulla, 
much  less  extensive  than  the  cortex,  presents  irregularly  shaped  cells, 
the  outlines  of  which  are  but  slightly  marked.  These  cells  contain 
granules  wliicli  stain  darkly  with  chromates  and  give  a  green  colour 
with  salts  of  iron.  It  is,  hence,  easy  to  delimit  the  area  of  the  cortex 
in  any  section  of  a  gland  which  has  been  hardened  in  a  fluid  containing 
chromates.  The  substance  giving  this  reaction  is  known  as  chromo- 
phile  or  chromaffiner  substance.  The  suprarenals  are  richly  supplied 
with  blood,  especially  in  the  medullary  part,  the  cells  of  which  impinge 
directly  on  the  endothelial  lining  of  dilated  capillaries.  They  also 
receive  an  abundant  nerve-supply  from  the  sympathetic  system,  the 
nerves  forming  a  thick  meshwork,  especially  in  the  medulla,  and 
presenting  at  intervals  ganglion-cells  which  may  be  isolated  or  com- 
bined to  form  small  ganglia. 

A  study  of  the  development  of  the  suprarenal  glands  shows  that  we 
have  here  to  do  with  two  distinct  tissues,  probably  differing  in  the  part 
they  play  in  the  animal  economy.  ^Vhereas  the  cortex  is  derived 
from  that  portion  of  the  mesoblast,  tlie  '  intermediate  cell  mass,'  from 
which  the  mesonephros  is  also  developed,  the  medulla  is  produced  bv 
an  outgrowth  from  the  sympathetic  system  and  may  be  said  indeed 
to  consist  of  profoundly  modified  nerve-cells.  )  In  many  fishes  these  two 
elements  of  the  suprarenal  gland  remain  serrated  throughout  life,  the 
cortex  being  represented  by  a  series  of  paired  interrenal  bodies  lying 
on  the  front  of  the  spinal  column,  and  the  medulla  by  a  number  of 
collections  of  chromaffine  cells  lying  in  close  juxtaposition  to  the  spinal 
nerves.  In  some  animals  accessory  suprarenals  are  not  infrequent 
in  which  both  cortex  and  medulla  may  be  represented.  In  all  animals 
we  find  masses  of  tissue,  the  so-called  paraganglia,  in  close  association 
with  the  sympathetic  system,  which  present  the  chromaffine  reaction 
typical  of  the  medulla.  Since  a  watery  extract  or  decoction  of  these 
bodies  has  the  same  influence  on  injection  into  the  blood-stream  as 
an  infusion  of  the  medulla  of  the  suprarenal  body  itself,  we  are 
probably  justified  in  regarding  these  bodies  as  equivalent  to  accessory 
medullary  portions  of  the  suprarenal.  They  have  the  same  origin,  the 
same  staining  reactions,  and  the  same  physiological  effect  as  the  latter. 

The   functions  of    the  suprarenal  bodies  were  a  matter  of  pure 


1322  PHYSIOLOGY 

hypothesis  before  Addison  in  1855  drew  attention  to  the  coincidence  of 
degenerative  destruction  of  these  bodies  Avith  a  disease  which  has  been 
known  since  that  time  as  Addison's  disease.  The  three  cardinal 
symptoms  of  this  disorder  are  (1)  bronzing  of  the  skin,  (2)  vomiting, 
(3)  excessive  muscular  weakness  and  prostration.  The  disease  is  almost 
invariably  fatal.  Addison's  observations  have  been  amply  con- 
firmed since  that  time,  but  we  are  not  yet  in  a  position  to  account  for 
the  occurrence  of  all  these  symptoms  as  a  result  of  interference  with 
the  cortex  and  medulla  of  the  suprarenals.  The  experimental  destruc- 
tion or  extirpation  of  these  bodies  has  naturally  been  frequently 
carried  out.  The  operation  always  leads  to  the  death  of  the  animal 
within  twelve  to  twenty-four  hours.  Even  when  the  destruction  is 
carried  out  by  degrees  it  has  been  impossible  to  reproduce  the  bronzing 
which  is  so  characteristic  of  Addison's  disease.  The  one  symptom 
which  is  observed  as  a  result  of  the  experimental  extirpation  is  the 
excessive  prostration,  which  is  attended  with  muscular  weakness  and 
a  lowered  blood-pressure.  In  a  few  cases  it  has  been  found  possible 
to  keep  rats  alive  after  total  extirpation  of  these  organs,  but  this 
result  is  probably  due  to  the  frequent  presence  in  these  animals  of 
accessory  suprarenals. 

In  a  series  of  experiments  on  frogs  in  which  the  suprarenals  were 
destroyed,  Langlois  found  that  the  blood  of  the  animals  dying  as  a 
result  of  the  operation  was  toxic  for  other  animals,  and  hastened 
death  if  injected  into  other  frogs  already  deprived  of  their  supra- 
renals. He  concluded  from  his  experiments  that  the  main  office  of 
the  suprarenals  was  to  destroy  some  poison  especially  affecting  the 
neuro-muscular  system,  which,  in  their  absence,  accumulates  in 
the  blood  and  brings  about  death.  Our  views  on  the  subject  of  the 
suprarenals  were  completely  modified  by  certain  observations  of 
Schafer  and  Oliver,  published  in  the  year  1894.  These  observers 
found  that  a  watery  extract  or  decoction  of  the  suprarenal  bodies, 
when  injected  into  the  circulation,  caused  a  very  great  rise  of  blood 
pressure,  brought  about  chiefly  by  constriction  of  all  the  blood-vessels 
of  the  body.  The  active  substance  responsible  for  this  rise  was 
found  to  be  limited  entirely  to  the  medulla,  infusions  of  the  cortex 
being  without  influence  on  the  blood  pressure.  Later  on  Takamine 
succeeded  in  isolating  the  active  substance,  to  which  he  gave  the 
name  of  adrenalin,  and  since  that  time  physiological  chemists  have 
succeeded  not  only  in  determining  the  constitution  of  adrenalin  but  also 
in  preparing  it  synthetically.  The  constitution  of  adrenalin  is  shown 
by  the  following  formula  : 
HO 

H0(^  ^— CH(OH)— CH2NHCH3 


THE  DUCTLESS  GLANDS  1323 

Since  it  possesses  an  asynimetric  carbon  atom,  a  substance  of  this 
formula  may  be  either  Isevo-  or  dextrorotatory.  Both  forms,  as  well 
as  the  racemic  modification,  have  been  prepared  synthetically.  The 
substance  which  occurs  in  the  suprarenal  gland  is  the  Isevorotatory 
modification,  and  Cushny  has  shown  that  it  is  only  this  modification 
which  is  active,  injection  of  the  dextrorotatory  compound  having 
only  one-twelfth  the  effect  of  the  IsBVorotatory.  Adrenalin  is  active 
in  excessively  minute  doses,  injection  of  one  four-hundredth  of  a  milli- 
gramme per  kilo  body  weight  sufficing  to  evoke  a  definite  rise  of 
blood  pressure.  On  injecting  it  into  the  circulation  there  is  imme- 
diately a  rise  of  blood  pressure  which,  if  the  vagi  are  intact,  is  only 
moderate  in  amount,  but  is  accompanied  by  a  marked  slowing  of  the 
heart.  This  excitation  of  the  vagus  is,  however,  probably  secondary 
to  the  rise  of  blood  pressure  and  is  not  due  to  direct  action  of  the  drug 
on  the  vagus  centre.  If  the  vagi  be  divided  the  injection  of  adrenalin 
evokes  a  huge  rise  of  pressure  which  may  amount  to  300  mm.  Hg.  It 
may  indeed  be  so  great  that  the  animal  dies  from  heart-failure  or 
from  pulmonary  oedema.  The  rise  of  pressure  is  observed  even  after 
destruction  of  the  central  nervous  system.  The  action  is  not,  how- 
ever, limited  to  the  blood-vessels.  It  has  been  shown  by  Langley  and 
by  Elliott  that  adrenalin  injected  into  the  circulation  arouses  every 
activity  which  can  be  normally  excited  by  stimulation  of  the  sympa- 
thetic system.  A  list  of  the  actions  of  adrenalin  is  therefore  identical 
with  a  list  of  the  chief  functions  of  the  sympathetic  nervous  system. 
In  the  head  it  causes  dilatation  of  the  pupil,  secretion  of  saliva,  and 
erection  of  the  hairs.  On  the  heart  it  has  a  strong  augmentor  and 
accelerator  influence,  so  that  the  heart  beats  more  effectively  as  a  rule 
even  against  the  enormously  increased  resistance  offered  by  the  con- 
stricted arterioles.  Whereas  a  rise  of  blood  pressure  generally  causes 
increased  systolic  volume  of  the  heart,  we  may  find  after  an  injection 
of  adrenalin  and  during  the  height  of  the  rise  of  blood  pressure  that 
the  heart  empties  itself  more  effectively  than  it  did  before  the  injection. 
On  the  lung-vessels  adrenalin  has  no  constrictor  influence,  which  is 
in  accordance  with  the  results  obtained  by  stimulating  the  svmpa- 
thetic  system.  With  regard  to  the  vessels  of  the  brain,  we  find  the 
same  divergence  of  opinion  as  in  the  case  of  excitation  of  possible 
vaso-motor  nerves  to  this  organ.  Some  observers,  on  perfusing  the 
brain  with  defibrinated  blood,  have  obtained  constriction  on  adding 
adrenalin  to  the  perfused  blood,  while  othere  have  been  unable  to 
obtain  any  positive  results  in  this  direction.  In  the  abdomen  intra- 
venous injection  of  adrenalin  causes  complete  relaxation  of  the  muscu- 
lature of  the  stomach,  small  and  large  intestines,  but  causes  contrac- 
tion of  the  ileocolic  sphincter.  On  the  bladder  its  effect  varies 
according  to  the  animal  studied,  but  in  every  case  is  identical  with  that 


1324  PHYSIOLOGY 

obtained  by  stimulating  the  hypogastric  nerves.  It  has  been  shown 
by  Dale  that  adrenalin  may  also  excite  vaso-dilator  fibres  or  produce 
vaso-dilator  effects  when  such  effects  are  also  obtained  from  stimula- 
tion of  the  sympathetic  nerves.  In  order  to  evoke  these  results  it  is 
necessary  to  paralyse  the  vaso-constrictors  by  the  injection  of  ergo- 
toxin,  one  of  the  active  principles  of  ergot.  This  drug,  when  injected, 
causes  first  active  vaso -constriction  and  rise  of  blood  pressure,  followed 
by  paralysis  of  the  vaso-constrictor  mechanism.  Excitation  of  the 
splanchnic  nerves  or  injection  of  adrenalin  will  now  bring  about  a  fall 
of  blood  pressure  due  to  dilatation  of  the  vessels  in  the  splanchnic  area. 

The  point  of  attack  of  the  adrenalin  appears  to  be  in  the  muscular 
or  glandular  tissues  themselves,  since  it  may  be  obtained  not  only 
after  destruction  of  the  cord  and  sympathetic  plexuses  but  even 
after  time  has  been  allowed  for  the  peripheral  (post-ganglionic)  fibres 
to  degenerate  as  a  result  of  extirpation  of  the  corresponding  ganglia. 
Although  the  effect  is  not  altered  under  these  circumstances,  and  it 
may  still  produce  either  relaxation  or  contraction  of  muscles  according 
to  the  original  action  of  the  sympathetic  on  these  fibres,  we  are  not 
justified  in  regarding  it  as  acting  on  the  contractile  material  of  the  cells 
themselves.  Rather  must  we  assume  with  Langley  and  Elliott  that 
the  action  of  adrenalin  is  on  some  substance  mediating  between  the 
nerve  and  the  responsive  tissue.  We  may  speak  of  this  reactive 
material  as  the  receptor  substance  (Langley),  or  we  may  locate  it  in 
the  situation  where  the  nerve  joins  the  muscle  or  gland-cell  and 
describe  adrenalin  as  acting  on  the  myoneural  junction.  Schafer  also 
mentioned  the  influence  of  adrenalin  on  voluntary  muscle,  but  later 
observers  have  failed  to  substantiate  any  marked  specific  influence  on 
this  tissue. 

When  adrenalin  is  injected  into  the  blood-stream  the  effect  is 
only  temporary.  It  is  not  excreted  in  the  urine,  but  rapidly  dis- 
appears from  the  blood.  Since  it  is  easily  oxidised  and  is  extremely 
unstable  in  alkaline  solution,  we  may  conclude  that  after  performing 
its  excitatory  function  it  is  destroyed  by  oxidation  in  the  fluids. 
Adrenalin  is  thus  a  typical  hormone,  a  body  of  comparatively  low 
molecular  weight,  having  a  drug-like  excitatory  action  on  specific 
tissues  of  the  body,  easily  diffusible,  and  rapidly  destroyed  after  dis- 
charging its  office.  Owing  to  the  rapid  destruction  of  adrenalin, 
relatively  enormous  doses  have  to  be  given  by  the  mouth  in  order  to 
produce  any  effect  on  the  blood  pressure.  There  is,  however,  a  whole 
series  of  substances,  more  or  less  allied  to  adrenalin  in  chemical  con- 
stitution, which  undergo  less  rapid  destruction  and  can  therefore  be 
administered  as  drugs  in  the  usual  way.  Dale  and  Barger  have 
recently  described  three  such  substances  as  occurring  in  infusions 
of  putrid  meat    and  as   forming  the  most  important    of  the  active 


THE  DUCTLESS  GLANDS  1325 

principles  of  ergot.     The  constitution  of  these  substances  is  shown  in 
the  following  foi-mulae  : 


CH 


)CHCH2CH2lSrH2  Isoamylamine 


CR/ 

H0(^ 

\_ 
/ 

-CH2CH2NH2 

\ 

\ 

-CH2CH2NH2 

HO 

ho/ 

\_ 

-CH(0H)CH2] 

p-hydroxyphenylethylamine 
phenylethylamine 


The  formula  of  adrenalin  is  placed  below  in  order  to  show  the 
relation  of  these  substances  to  the  natural  hormone.  These  bodies  are 
produced  from  the  amino-acids  of  proteins  by  a  process  of  decarboxyla- 
tion. Leucine  would  yield  isoamylamine,  tyrosine,  hydroxyphenyleth- 
ylamine,  and  phenylalanine  would  give  phenylethylamine.  Such 
substances  may  be  formed  in  minute  quantities  during  the  normal 
processes  of  putrefaction  which  occur  in  the  alimentary  canal.  There 
seems  little  doubt  that  we  must  regard  adrenalin  as  a  true  internal 
secretion,  and  therefore  must  ascribe  to  the  medulla  of  the  suprarenal 
capsules,  as  well  as  to  the  other  chromaflBue  tissue  in  the  body,  the 
function  of  maintaining  the  normal  constriction  of  the  arterioles  and 
of  facilitating  in  some  way  or  other  the  functions  of  the  sympathetic 
system  generally.  The  absence  of  this  secretion  in  cases  of  destruction 
by  disease  of  the  suprarenals  would  serve  to  account  for  the  weakness, 
prostration,  and  lowered  blood  pressure  of  Addison's  disease.  The 
two  other  symptoms  of  this  disease,  namely,  bronzing  and  vomiting, 
still  remain  to  be  accounted  for.  It  is  possible  that  the  latter  may 
be  due  to  some  involvement  by  the  morbid  process  of  the  numberless 
fibres  of  the  solar  plexus,  which  run  in  close  proximity  to  the  supra- 
renals. We  have  no  knowledge  whatsoever  of  the  functions  of  the 
cortical  power  of  these  organs.  It  is  possible  that  future  work  may 
show  some  connection  between  the  cortex  and  the  destruction  of  pig- 
ment in  the  body.  At  present  it  is  only  by  a  process  of  exclusion  that 
we  may  guess  at  a  causal  relationship  between  the  destruction  of  the 
cortex  and  the  bronzing  which  occurs  in  Addison's  disease. 

THE  THYROID  GLAND   AND   THE   PARATHYROIDS 
The  thyroid  gland  consists  of  two  oval  bodies  lying  on  either 
side  of  the  trachea,  joined  in  many  animals  across  the  trachea  by  an 


1326 


PHYSIOLOGY 


isthmus.  Surrounded  by  a  capsule  of  connective  tissue,  it  is  made  up 
of  an  aggregation  of  vesicles  varying  in  size  from  15  to  150  /u.  The 
vesicles  are  lined  by  a  single  layer  of  cubical  epithelial  cells,  and  are 
filled  with  a  translucent  material  known  as  colloid  (Fig.  544).  Of  the 
cells,  some  present  granules  and  resemble  the  cells  of  a  secreting  gland, 
while  others  contain  masses  of  colloid,  or  have  undergone  colloidal 
degeneration.  Between  the  vesicles  may  be  seen,  here  and  there,  solid 
masses  of  cells  which  by  some  observers  are  regarded  as  destined  to 
replace  vesicles  the  epithelium  of  which  has  undergone  complete  degene- 
ration. The  colloid  material  can  be  traced  between  the  cells  into  the 
lymphatics  lying  between  the  vesicles.  Since  the  gland  possesses  no  duct 


Fig.  544.     Section  of  thyroid  gland  of  dog.    (Swale  Vincent.) 

it  is  supposed  that  the  cells  furnish  an  internal  secretion,  which  makes 
its  way  into  the  blood  along  the  lymphatic  efferents  of  the  gland. 
The  thyroid  is  richly  supplied  with  blood  by  the  superior,  middle,  and 
inferior  thyroid  arteries,  and  is  surrounded  with  a  plexus  of  veins  lying 
immediately  under  the  capsule.  In  development  the  thyroid  is  formed 
by  an  outgrowth  from  the  fore-gut,  but  the  connection  with  the  gut  dis- 
appears long  before  the  end  of  foetal  life.  In  rare  cases  part  of  the 
duct  may  persist,  and,  becoming  gradually  filled  with  fluid,  give  rise 
to  a  hyoid  cyst  which  lies  below  the  tongue  and  may  require  excision 
by  the  surgeon. 

As  in  the  case  of  the  other  ductless  glands,  clinical  observations 
have  contributed  materially  to  our  knowledge  of  the  functions  of  the 
thyroid.  Although  the  gland  had  been  extirpated  in  animals  by 
Astley  Cooper  and  by  Schiff,  the  attention  of  physiologists  and  medical 
men  was  especially  directed  to  the  importance  of  this  organ  by  the 
observations  of  surgeons,  especially  Kocher,  on  the  untoward  and  even 
fatal  effects  following  its  complete  removal  in  man  in  operations  for 
extirpation  of  goitre.  In  this  country  attention  had  already  been 
called  to  the  connection  of  a  disturbed  condition  of  metabolism  known 


THE  DUCTLESS  GLANDS  L327 

as  myxoedema  with  atrophy  of  the  thyroid.  A  patient  affected  with 
myxa3dema  presents  a  gradually  increasing  blunting  of  his  or  her 
mental  activities  ;  speech  is  slow,  cerebration  delayed.  With  this 
nervous  defect  are  associated  changes  in  the  connective  tissues, 
the  subcutaneous  connective  tissue  becoming  thickened,  so  that 
the  face  and  hands  appear  swollen  and  puffy,  looking  at  first 
sight  as  if  cedema  were  present.  The  swelling  is,  however,  due 
to  newly  formed  coniu^ctive  tissue,  and  not  to  the  presence  of 
an  excess  of  interstitial  fluid  in  the  tissues.  The  patient  often 
presents  a  yellow,  waxy  appearance  with  a  patch  of  colour  on  the 
cheeks.  The  hair  falls  out,  the  pulse  is  slowed,  and  the  temperature 
tends  to  be  subnormal  owing  to  the  diminution  of  the  rate  of  meta- 
bolism in  the  body.  The  intake  of  food  and  the  excretion  of  urea  are 
diminished.  If  the  atrophy  of  the  thyroid  occurs  in  early  life  during 
the  period  of  growth,  e.g.  in  young  children,  the  growth  of  the  skeleton 
practically  ceases.  The  bones  of  the  limbs  may  grow  in  thickness  but 
not  in  length.  There  is  early  synostosis  of  the  bones  of  the  skull, 
and  complete  cessation  of  development  of  mental  powers.  Children 
80  affected  may  live  for  many  years,  but  when  twenty-five  or  thirty 
present  still  a  childish  appearance  (Fig.  545,  c).  Stunted,  pot-bellied, 
and  ugly,  they  have  the  intelligence  of  a  child  of  four  or  five.  They  often 
present  fatty  tumours  above  each  clavicle,  and  similar  subcutaneous 
tumours  of  fat  or  loose  fibrous  tissue  are  found  in  cases  of  myxoedema 
in  the  adult. 

When  the  thyroid  is  extirpated  in  man  the  result  is  often  the 
production  of  typical  myxojdema.  In  some  cases,  especially  in  young 
individuals,  the  results  are  more  severe,  a  condition  of  tetany  being 
set  up  in  which  there  are  tonic  spasms  of  the  muscles  of  the  body, 
especially  of  the  extremities.  When  the  thyroid  gland  is  extirpated 
in  animals  the  results  more  closely  resemble  these  acute  cases.  In 
certain  cases  a  chronic  condition  of  malnutrition  is  set  up,  but  a 
typical  myxoedema  with  thickening  of  the  subcutaneous  tissues  by 
new  growth  of  connective  tissue  has  only  been  described  by  Horsley 
in  monkeys.  The  effects  are  more  pronounced  in  carnivora  than  in 
herbivora.  In  the  former  a  condition  of  tetany  is  produced  accom- 
panied with  muscular  tremors  and  clonic  convulsions  which  come  on 
at  intervals  and  may  be  accompanied  with  severe  dyspnoea  leading 
to  death  within  fourteen  days.  In  herbivora,  wasting,  diminution  of 
respiratory  exchange,  and  disorders  of  nutrition  are  often  the  most 
pronxinent  symptoms.  These  results  have  been  ascribed  by  Munk 
to  interference  with  the  recurrent  laryngeal  nerves  during  the 
operations,  but  the  observations  on  man  leave  very  little  doubt  that 
they  are  due  entirely  to  the  removal  of  the  chemical  influence  of  the 
thyroid  gland.     Many  authorities  were  at  first  inclined  to  ascribe 


1328  PHYSIOLOGY 

these  results  in  man  and  animals  to  the  circulation  in  the  blood  of  toxic 
substances  which  would  normally  undergo  destruction  in  the  thyroid 
gland.  This  theory  is  put  out  of  court  by  the  results  of  administra- 
tion of  thyroid  gland  to  patients  with  myxoedema  or  to  animals  deprived 
of  their  thyroids.  SchifE  first  showed  that  the  effects  of  extirpation  of 
the  thyroid  might  be  prevented  if,  at  the  same  time,  the  thyroid  from 
another  animal  were  transplanted  into  the  subcutaneous  tissue  to 
take  the  place  of  the  one  removed.  On  removing  the  transplanted 
thyroid,  the  typical  symptoms  of  thyroid  destruction  at  once  ensued. 


Fig.  545.  a,  a  cretin,  23  months  old.  b,  the  same  child,  34  months  old,  after 
administration  of  sheep's  thyroids  for  11  months,  c,  a  cretin,  untreated, 
15  years  old.     (W.  Osler.) 


It  was  later  found  that  similar  good  results  could  be  obtained  by  sub- 
cutaneous injection  oi  the  expressed  juice  of  the  thjrroid,  and  later 
that  even  this  was  not  necessary,  and  that  it  was  sufficient  to 
administer  the  thyroid  gland,  either  fresh,  dried,  or  partially  cooked, 
by  the  mouth.  The  administration  of  the  thyroid  gland  in  this  way  is 
indeed  one  of  the  therapeutic  triumphs  of  the  last  twenty  years.  An 
ugly  and  idiotic  cretin  can  be  converted  in  this  way  into  a  child  of 
ordinary  intelligence  with  normal  powers  of  growth  (Fig.  545).  Given 
to  myxoedemic  patients,  the  thyroid  gland  reduces  the  swelling  of  the 
subcutaneous  tissues,  causes  a  new  growth  of  hair,  and  restores  the 
patient  to  his  or  her  former  state  of  mental  health.  Nor  is  the  thyroid 
gland  without   influence   on  the  healthy   individual.      If  given  in 


THE  DUCTLESS  GLANDS  1329 

large  doses  either  to  man  or  animab,  it  quickens  the  pulse,  even 
causing  violent  palpitation,  and  increases  the  metabolic  activities  of 
the  body,  so  that  the  appetite  is  increased,  the  nitrogenous  output 
rises  above  the  intake,  and  the  subcutaneous  fat  is  diminished 
or  disappears.  It  is  possible  that  a  moderate  degree  of  thyroid 
inadequacy  is  not  infrequent  and  that  the  beneficial  effects  on  general 
health,  in  removing  excessive  corpulence  and  in  promoting  the  growth 
of  hair,  which  are  observed  on  administering  the  drug  to  people  of 
middle  life,  may  be  due  to  the  actual  replacement  of  a  function  which 
is  being  insufficiently  discharged.  The  symptoms  caused  by  excessive 
doses  of  thyroid  gland  are  strikingly  similar  to  those  occurring  in  the 
disease  known  as  exophthalmic  goitre,  where  there  is  a  true  hyper- 
trophy of  the  gland  associated  with  cardiac  palpitation,  proptosis 
(bulging  of  the  eyes),  wasting,  and  muscular  weakness. 

All  these  facts  warrant  us  in  including  the  thyroid  body  among 
the  glands  with  an  internal  secretion,  the  presence  of  which  in  the 
blood-stream  is  a  necessary  condition  for  the  normal  growth  and  func- 
tions of  almost  all  the  tissues  of  the  body.  If  this  secretion  is  lacking 
we  obtain  the  condition  known  as  myxoedema  in  adults,  as  cretinism 
in  young  children.  If  it  be  present  in  excess  the  symptoms  of  exoph- 
thalmic goitre  are  produced.  The  exact  character  of  the  internal 
secretion  cannot  be  regarded  yet  as  definitely  established.  It 
seems  possible  that  it  is  identical  with  a  substance  containing  iodine 
in  organic  combination,  which  was  isolated  by  Baumann  from  the 
thyroid  gland  and  is  known  as  iodothyrin.  In  certain  experiments 
the  results  of  administration  of  iodothyrin  were  found  to  be  identical 
with  those  obtained  by  giving  the  whole  gland.  Doubt  has  been 
thrown  on  the  specific  nature  of  this  body  on  account  of  the  fact 
that  iodine  may  be  wanting  in  the  thyroid  gland  in  certain  animals, 
though  Reid  Hunt  has  shown  that  the  physiological  effects  of  thyroid 
extract  are  proportional  to  the  amount  of  iodine  contained  therein. 

SIGNIFICANCE  OF  THE  PARATHYROIDS.  The  parathyroids 
are  small  bodies,  varying  in  number,  situated  on  the  border  of  the 
thyroid  gland  or  actually  embedded  in  its  substance.  In  histological 
appearance  they  differ  widely  from  the  thyroid,  and  consist  of  solid 
masses  or  columns  of  epithelial  cells  surrounded  with  connective  tissue 
and  richly  supplied  with  blood-vessels  (Fig.  546).  Considerable  diver- 
gence of  opinion  still  exists  as  to  the  significance  of  these  bodies.  In 
some  animals,  e.g.  in  the  dog,  where  they  are  embedded  in  the  gland, 
they  will  be  necessarily  removed  in  any  operation  for  the  extirpation 
of  the  thyroid.  In  others,  such  as  the  rabbit,  where  they  lie  outside 
the  gland,  it  is  easy  to  avoid  them  in  the  excision  of  the  thvToid. 
To  this  varying  distribution  of  the  parathyroids  have  been  ascribed 
the  different  results  of  extirpation  of  the  thyroid  in  carnivora  and 

84 


1330  PHYSIOLOGY 

herbivora  respectively.  Forsyth  has  shown  that,  in  man,  the  situation 
of  the  parathyroids  corresponds  ahnost  exactly  with  the  places  in  which 
are  fonnd  occasionally  accessory  thyroids  ;  and,  according  to  Edmunds, 
after  excision  of  the  thyroid,  the  parathyroids  undergo  histological 
alteration  and  are  converted  into  thyroid  tissue,  the  cells  taking  on  an 
alveolar  arrangement  and  producing  colloid  material.  According  to 
this  view  the  parathyroids  would  represent  simply  immature  thyroid 
tissue.  On  the  other  hand,  it  has  been  suggested  (Biedl)  that  the  para- 
thyroids have  a  function  entirely  distinct  from  that  of  the  thyroid 


end.  .• SPfe^/ 


k        -^"^"^     "' 


5?  *.   ^  4m 


A 


,.'«•;* 


end  •  ■' 


•  «  *  . 


Fig.  546.     Section  of  parathyroid.     (I^N.)  /  ^v  f^  ^'  f^' 
ep,  secreting  epithelium  ;    pig,  cells  containing  pigment ;    cap,  sinus-like 
capillaries  ;    end,  endothelial  cells. 

gland,  removal  of  the  thyroids  jjroducing  simply  a  condition  of 
cachexia  and  the  changes  associated  with  myxoedema,  while  removal 
of  the  parathyroids  is  responsible  for  the  nervous  disturbaiices  and 
tetany  observed  after  total  extirpation  of  these  organs.  The  matter 
cannot  yet  be  regarded  as  definitely  settled. 

THE  PITUITARY  BODY 

The  pituitary  body  consists  of  two  parts  which  have  separate 

modes  of  origin.     An  outgrowth  from  the  buccal  cavity  in  the  embryo 

meets  a  hollow  extension  of  the  anterior  cerebral  vesicle.     The  buccal 

ectoderm  gives  rise  to  the  anterior  lobe  and  pars  intermedia  of  the 


THE  DUCTLESS  GLANDS 


1331 


pituitary,  while  the  neural  epiblast  becomes  developed  into  the  pos- 
terior lobe  (Fig.  547).  In  some  animals  the  posterior  lobe  remains  hollow 
and  retains  its  primitive  connection  with  the  tiiird  ventricle  of  the 
brain,  but  in  man  it  becomes  entirely  solid.  The  anterior  lobe  in  the 
adult  consists  of  nests  of  epithehal  cells  (Fig.  548),  many  of  which  are 
filled  with  granules,  and  is  richly  supplied  with  large,  thin-walled  capil- 
lary blood-vessels.  The  anterior  lobe  is  separated  from  the  posterior 
lobe  by  a  cleft  which  is  the  remains  of  the  original  hollow  outgrowth 
from  the  buccal  cavity.  The  epithelial  tissue  immediately  surrouiiding 
this  cleft  differs  somewhat  from  that  constituting  the  anterior  lobe.  The 


Fig.  547.    Mesial  sagittal  section  through  the  pituitary  body  of  an  adult  monkey 
(semi-diagrammatic).     (After  Herring.) 
a,  optic  chiasma  ;   b,  third  ventricle  ;   c,  tongue-like  process  of  pars  inter- 
media ;    d,  epithelial  investment  of  posterior  lobe  ;    e,  anterior  lobe  ;  /,  epi- 
thelial cleft ;   g.  pars  intermedia  ;   h,  posterior  lobe. 


cells,  which  present  but  few  granules,  are  arranged  in  islets,  separated 
by  an  intervening  tissue  continuous  with  the  main  mass  of  the  posterior 
lobe.  Many  of  the  islets  are  hollow  and  enclose  a  colloid  material.  The 
colloid  material  has  been  traced  by  Herring  into  the  interalveolar 
connective  tissue  and  into  the  prolongation  of  the  infundibulum  which 
enters  the  posterior  lobe.  One  must  therefore  conclude  that  the 
colloid  material  secreted  by  the  cells  of  this  part  passes  directly  into  the 
third  ventricle.  The  amount  of  colloid  material  increases  in  animals 
whicli  have  undergone  extirpation  of  the  thyroid  gland. 

Our  first  clue  to  the  importance  of  this  organ  in  the  normal  pro- 
cesses of  the  body  was  furnished  by  the  observations  of  Pierre  Marie, 
who  found  that  the  morbid  condition  of  '  acromegaly  '  is  associated 


1332  PHYSIOLOGY 

with  tumours  of  the  pituitary  gland.  This  disease  consists  in  an 
increased  growth  of  certain  parts  of  the  skeleton,  especially  the  lower 
jaw  and  the  extremities  of  the  limbs.  Headache  is  often  present, 
and  there  may  be  polviiria  and  affection  of  the  eyesight.  When  this 
disease  occurs  during  the  period  of  active  growth  there  may  be  an 
increase  in  length  both  of  the  limb-bones  and  of  the  trunk,  and  most  of 


-  ^ 


1 


^ 


\ 


\ 


Fig.  548.     Section  of  cat's  pituitary  bodj%  passing  through  the  cleft  in  the  gland. 

(P.  T.  Herring.) 
a,  pars  anterior ;   6,  cleft ;   c,  pars  intermedia  ;   d,  pars  nervosa  (posterior 

lobe). 

the  giants,  which  are  shown  from  time  to  time,  are  examples  of  this 
pathological  condition  of  '  gigantism.'  Opinions  have  differed  whether 
this  condition  is  due  to  an  over-action  or  to  a  failure  of  action  on  the 
part  of  the  gland.  Experiments  on  extirpation  of  the  gland  have  not 
solved  the  problem.  Total  extirpation  of  the  pituitary  body  is 
generally  followed  by  death  within  a  few  days,  death  which  cannot  be 
attributed  to  shock  or  any  accidental  features  of  the  operation.  One 
must  regard  the  pituitary  therefore  as  essential  to  the  maintenance 
of  life.  It  has  not  been  possible  by  transplantation  to  replace  a 
removed  pituitary  body,  since  the  transplanted  organ  has  hitherto 
always  undergone  degeneration.  In  some  cases  Gushing  succeeded  in 
prolonging  the  period  of  survival  after  extirpation  of  the  pituitary 


THE  DUCTLESS  GLANDS  1333 

by  the  transplantation  of  the  gland  from  other  animals  into  the  brain 
substance. 

The  most  definite  evidence  we  have  as  to  the  mode  of  action  of 
the  different  parts  of  the  pituitary  gland  has  been  furnished  by  experi- 
ments on  administration  or  injection  of  the  dried  gland  or  its  extracts. 
The  posterior  lobe  seems  to  be  practically  inactive,  extracts  made 
from  this  lobe  having  the  same  influence  as  extracts  from  nervous  tissue 
generally.  If,  however,  the  intermediate  epithelial  substance  is 
included  in  the  posterior  lobe,  marked  effects  may  be  obtained  from 
the  intravenous  injection.  An  extract  of  the  posterior  lobe  (including 
pars  intermedia)  produces,  as  was  shown  by  Schafer,  a  rise  of  blood 
pressure  and  diuresis.  The  latter  result  also  follows  administration  of 
the  posterior  lobes  by  the  mouth.  Dale  has  shown  that  the  active 
principle  exercises  a  direct  excitatory  effect  on  all  unstriated  muscle, 
the  effect  being  unaltered  whether  the  nerve-supply  to  the  muscle  be 
present  or  not.  Thus  it  produces  contraction  of  the  blood-vessels, 
of  the  intestinal  muscle,  and  of  the  uterus,  and  will  act  upon  mus- 
cular tissues,  such  as  the  arteries  of  the  lungs  or  heart,  which  do 
not  receive  constrictor  impulses  from  the  sympathetic  system.  The 
active  principle  is  much  more  stable  than  the  other  hormones  we 
have  already  studied.  It  is  not  destroyed  by  boiling,  and  after 
injection  into  the  blood-stream  can  be  recovered  from  the  urine.  It 
is  possible  that  the  polyuria,  which  is  not  infrequently  observed 
in  association  with  head  injuries  or  tumours  of  the  brain,  may  be 
occasioned  by  an  increased  escape  of  this  material  into  the  general 
circulation. 

Extracts  from  the  anterior  lobe  have  no  definite  effect  when 
injected  into  the  blood-stream.  It  has  been  shown  by  Schafer  that 
the  addition  of  the  anterior  lobe  of  the  pituitary  body  to  the  food  of 
young  growing  animals  causes  an  increased  rate  of  growth.  In  this 
experiment  eight  rats  of  a  litter  were  taken  :  four  were  fed  with 
bread  and  milk  to  which  the  anterior  lobes  of  pituitary  bodies  had 
been  added,  while  the  other  four,  which  served  as  controls,  received 
bread  and  milk  with  a  corresponding  quantity  of  testis  or  ovary. 
According  to  Mackenzie  extracts  of  the  pituitary  body  have  a  marked 
excitatory  effect  on  the  secretion  of  milk  by  the  mammary  glands. 

It  is  evident  that  much  further  work  is  necessary  before  we  can 
regard  the  functions  of  the  pituitary  body  as  definitely  ascertained. 
The  evidence  we  have  at  present  would  seem  to  point  to  the  following 
conclusions  : 

(a)  The  anterior  lobe  furnishes  some  substance  to  the  circulation 
which  promotes  growth  especially  of  the  bony  and  connective  tissues 
of  the  body. 

(6)  The  intermediate  part  surrounding  the  cleft  between  anterior 


1334  PHYSIOLOGY 

and  posterior  lobes,  in  addition  to  the  production  of  some  substance 
which  is  a  general  excitant  for  unstriated  muscle  and  produces  diuresis, 
also  furnishes  a  colloid  secretion  which  passes  directly  into  the  ven- 
tricles of  the  brain  and  may  be  assumed  to  have  some  influence  on 
the  growth  or  functions  of  the  central  nervous  system.  Schafer 
regards  the  principle  giving  rise  to  diuresis  as  distinct  from  that 
causing  contraction  of  unstriated  muscle,  since  diuresis  may  occur 
without  corresponding  rise  of  blood  pressure.  The  independence  of 
the  two  phenomena,  renal  and  vascular,  cannot  be  regarded  as  proved. 

(c)  The  posterior  lobe  consists  mainly  of  neuroglia.  We  have  no 
clue  to  its  functions  apart  from  the  masses  of  intermediate  cells  which 
it  may  contain. 

Very  little  can  be  said  as  to  the  other  ductless  glands.  The  thymus 
forms  two  large  masses  in  the  anterior  mediastinum  which  in  man 
grow  up  to  the  second  year  of  life  and  then  rapidly  diminish  so  that 
only  traces  are  to  be  found  at  puberty.  It  contains  a  large  amount 
of  lymphatic  tissue  and  is  therefore  often  associated  with  the  lym- 
phatic glands  as  the  seat  of  formation  of  lymph-corpuscles.  The 
epithelial  remains  of  Hassall's  corpuscles  found  in  the  medullary  part 
of  its  globules  have  not  had  any  function  assigned  to  them.  In  certain 
cases  of  arrested  development  or  of  general  weakness  in  young  people 
the  thymus  has  been  found  to  be  persistent.  The  effect  of  extracts 
made  from  the  thymus  do  not  differ  from  those  of  extracts  made  from 
any  other  cellular  organ. 

The  pineal  gland  has,  so  far  as  we  know,  no  functions  in  meta- 
bolism. It  is  interesting  as  a  vestigial  remnant  of  a  primitive  dorsal 
eye.  In  certain  lizards  this  organ  still  presents  traces  of  its  original 
structure,  and  is  found  to  conform  to  the  invertebrate  type  of  eye.  It 
is  doubtful  whether  at  any  time  in  the  history  of  vertebrates  the  pineal 
eye  has  been  functional. 

The  carotid  and  coccygeal  glands  have  often  been  grouped  with 
the  collections  of  chromophile  cells  already  described  as  associated 
with  the  sympathetic  system.  Their  structure  resembles  more  nearly 
that  of  the  parathyroid  bodies  or  the  anterior  lobe  of  the  pituitary 
gland.  They  consist  of  a  small  collection  of  columns  or  masses  of 
cells  bound  together  by  connective  tissue  with  a  rich  supply  of  blood- 
capillaries.     Nothing  is  known  as  to  their  function. 

The  lymph  and  hsemolymph  glands,  and  the  spleen,  are  often 
grouped  with  these  ductless  glands.  The  essential  activity  of  these 
bodies,  however,  lies  in  the  production,  not  of  a  diffusible  chemical  sub- 
stance, but  of  fonned  elements,  e.g.  lymph-corpuscles,  and  they  do 
not  properly  fall  within  the  scope  of  this  chapter.  As  a  matter  of 
convenience,  we  may  deal  shortly  here  with  the  functions  of  the 
spleen. 


THE  DUCTLESS  GLANDS 


1335 


THE  SPLEEN 
This  organ  is  siiuilar  in  many  respects  to  a  lymphatic  gland.  It  is 
formed  of  a  framework  of  connective  tissue  and  unstriated  muscular 
fibres,  in  the  interstices  of  which  is  contained  the  splenic  pulj).  This 
consists  of  a  fine  fibrillar  network,  on  the  fibrils  of  which  lie  endo- 
thelial cells.  The  meshes  contain  the  cells  of  the  splenic  pulp,  which 
are  fairly  lariie  polygonal  cells,  and  leucocytes.  Just  as  in  a  l3anphatic 
gland  the  cellular  elements  of  the  tissues  are  bathed  by  the  lymph 
which  flows  through  the  gland,  so  in  the  spleen  the  walls  of  the  capil- 
laries become  discontinuous,  and  the  blood  is  poured  out  into  the 
interstices  of  the  tissue.  The  spleen  is  therefore  the  only  tissue  in  the 
body  where  the  blood  comes  in  actual  contact  with  the  tissue-elements 


Carotid 

Doc. 8  5  Kilo  ALL  connections  with  spllen 

SEVERED   EXCEPT  ONE  ARTERY  &   VEIN  ^<- 
0  PRESSURE 


I'''io.  549.     Plc'thysmographic  tracingof  spleen  (u^jpcr  curve)  from  a  dog,  showing 
the  spontaneous  contractions  of  this  organ  (reduced  from  a  tracing  by  Schafkr). 


themselves.  The  blood  from  the  splenic  pulp  is  collected  into  large 
venous  sinuses,  which  run  along  the  trabeculaB  to  the  hilum,  where 
they  unite  to  form  the  splenic  vein.  The  arteries  to  the  spleen  are 
beset  in  their  course  along  the  trabecule)  with  small  nodules  of  hiuphoid 
tissue,  which  are  known  as  the  Malpighian  follicles. 

It  is  evident  that  the  blood  must  meet  with  considerable  resistance 
in  passing  through  the  close  meshwork  of  the  splenic  pulp.  In  order 
to  ensure  a  constant  circulation  through  the  gland,  the  muscular 
tissue  of  the  capsule  and  trabecula)  has  the  property  of  rhythmic 
contraction.  If  the  spleen  be  enclosed  in  a  plethysmograph,  or  splenic 
oncometer,  and  its  volume  be  recorded  by  connecting  this  with  an 
oncograph,  it  will  be  seen  to  be  subject  to  a  series  of  large,  slow 
variations,  each  contraction  and  expansion  lasting  about  a  minute, 
and  recurring  with  great  regularity  (Fig.  541)).  Superposed  on 
these  large  waves  are  smaller  undulations  due  to  the  respiratory 
variations  of  the  blood  pressure,  and  on  these  again  the  little  excur- 
sions corres[)onding  to  each  heart-beat.  The  contractile  power  of 
the  spleen  is  under  the  control  of  tli(>  nervous  system,  and  a  ra[)id 


1336 

contraction  may 
nerves. 


PHYSIOLOGY 

be     induced    by   stimulation    of     the    splanchnic 


FUNCTIONS  OF  THE  SPLEEN 
The  structure  of  this  organ  suggests  that  the  splenic  cells  must 
exercise  a  constant  influence  on  the  blood  which  surrounds  them,  and 
that  this  influence  is  not  purely  of  a  chemical  nature.  In  the  liver  and 
kidneys,  which  exercise  so  powerful  an  efiect  on  the  composition  of 
the  blood  passing  through  them,  the  proper  cells  of  the  organs  are 
separated  from  the  blood-stream  by  the  capillary  wall.  Microscopic 
examination  of  the  cells  of  the  splenic  pulp  shows  us  that  these  are 
full  of  particles  of  brown  pigment  or  fragments  of  red  corpuscles 
(Fig.  550).     In  many  cases  of  infectious  disease,  such  as   recurrent 


Fig.  550.     Cells  from  a  scraping  of  the  spleen.     (Kolliker.) 
A,  splenic  pulp-cell  containing  red  blood-corpuscles,  6  (J:  =  nucleus) ;    B, 
leucocyte  with  polymorphous  nucleus  ;   c,  pulp-cell  contammg  disintegrated 
red  corpuscles  ;   D,  lymphocyte  ;    E.  giant  cell  ;   r,  nucleated  red  corpuscles  ; 
G,  normal  red  corpuscle  ;    E,  multinuclear  leucocyte  ;    J,  eosinophile  cell. 

fever,  the  splenic  cells  are  observed  towards  the  end  of  the  attack  to 
be  full  of  the  organism — ^spirillum — which  is  the  cause  of  the  disease. 
In  fact,  these  cells  are  so  arranged  that  they  can  take  up  solid  par- 
ticles held  in  suspension  in  the  blood-plasma.  We  must  indeed  look 
upon  the  spleen  as  the  great  blood-filter,  purifying  the  blood  in  its 
passage  by  taking  up  particles  of  foreign  matter  and  effete  red  cor- 
puscles. The  process  of  phagocytosis,  which  was  described  under 
the  cellular  mechanisms  of  defence  (p.  1145),  is  in  the  spleen  a  normal 
occurrence. 

A  function  has  also  been  assigned  to  the  spleen  in  the  formation 
of  red  blood-corpuscles,  but  the  evidence  is  not  sufficient  to  determine 
whether  such  a  process  occurs  normally. 

Chemical  analysis  of  the  spleen  reveals  the  presence  of  a  large 
number  of  what  are  called  extractives,  such  as  succinic,  formic, 
butyric,   and  lactic  acids,   inosit,   leucine,   xanthine,   hypoxanthine, 


THE  DUCTLESS  GLANDS  l.i.JT 

and  uric  acid.  There  is  also  a  protein  allied  to  alkali-albumen, 
combined  with  iron,  as  well  as  several  pigments  probably  derived  from 
the  hsemoglobin  of  the  red  corpuscles  destroyed  by  the  cells  of  the 
splenic  pulp.  The  fact  that,  in  cases  where  the  spleen  is  pathologically 
enlarged  as  in  leucocythsemia,  the  uric  acid  in  the  urine  is  largely 
increased,  points  to  a  connection  between  the  spleen  and  the  formation 
of  uric  acid  in  the  body.  The  numerous  extractives  which  are  formed 
probably  owe  their  origin  to  the  destructive  changes  effected  on 
the  effete  constituents  of  the  blood  by  the  agency  of  the  splenic 
pulp-cells. 


BOOK  IV 
KEPRODUCTION 


CHAPTER   XXI 
THE  PHYSIOLOGY  OF  REPRODUCTION 

SECTION  I 

THE  ESSENTIAL  FEATURES  OF  THE  SEXUAL 
PROCESS 

The  two  fundamental  characteristics  of  protoplasm,  which  distinguish 
it  above  all  others  from  unorganised  matter,  are  groivth  and  activity. 
Growth  occurs  at  the  expense  of  surrounding  non-living  material, 
while  activity  is  in  every  case  an  adapted  reaction  to  changes  in 
the  environment.  The  second  characteristic  would  seem  to  involve 
a  limitation  of  the  first,  and  does,  in  fact,  determine  the  conditions 
under  which  it  may  occur.  In  the  process  of  growth  of  a  minute 
spherical  mass  of  protoplasm  its  bulk  and  mass  increase  as  the 
cube,  while  the  surface  only  increases  as  the  square,  of  the  radius. 
Thus  the  proportion  of  surface  to  mass  diminishes  with  increased  size 
of  the  protoplasmic  unit,  and  since  activity  is  a  function  of  the  surface 
the  larger  the  unit  the  smaller  must  be  its  activity.  It  follows  that 
there  must  be  a  limiting  size  to  the  living  protoplasmic  unit,  and  it 
is  on  this  account  that  practically  no  unicellular  animal  or  plant 
exceeds  a  fraction  of  a  millimetre  in  diameter.  If  an  organism  is  to 
attain  any  larger  size,  this  can  only  be  by  a  multiplication  of  units, 
each  presenting  the  same  amount  of  surface  as  a  complete  unicellular 
organism,  though  the  surface  may  be  exposed  to  an  internal  and  not 
to  an  external  medium.  Another  factor,  limiting  the  size  of  the 
unicellular  organism  or  of  the  unit  of  the  niulticellular  organism,  is  the 
necessity  for  maintaining  a  certain  proportion  between  the  size  of 
the  nucleus  and  that  of  the  cytoplasm  composing  the  body  of  the  cell. 
Observations  on  artificial  division  of  cells  have  sho^^^^  us  that  the 
functions  of  digestion,  assimilation,  and  gro\\^.h  depend  upon  the 
presence  of  a  nucleus.  Hence,  when  for  any  reason  it  is  advantageous 
that  a  cell  should  attain  a  large  size,  such  a  cell  is  almost  always  foimd 
to  contain  many  nuclei.  All  the  '  giant  colls  '  found  in  the  body  of  man 
under  normal  or  pathological  conditions  are  also  multinuclear. 

Thus  the  continuous  display  of  the  functions  of  assimilation  and 


1342  PHYSIOLOCxY 

dissimilation,  of  growth  and  activity,  is  only  possible  so  long  as  cell 
division  keeps  pace  with  growth.  In  unicellular  organisms,  under 
favourable  conditions,  this  growth  and  multiplication  occur  with 
prodigious  rapidity.  It  has  been  computed  that  a  paramoecium, 
freely  supplied  with  food  material,  would,  by  gro^iih  and  division,  in 
the  course  of  a  year  form  a  mass  of  protoplasm  the  size  of  the  earth, 
assuming  of  course  that  no  accidents  or  destructive  agencies  intervened 
to  destroy  the  paramoecia  which  were  being  formed.  This  computa- 
tion, which  may  seem  a  fanciful  one,  is  useful  as  indicating  the  enor- 
mous number  of  individuals  brought  under  the  action  of  natural 
selection,  which  very  few  survive.  In  unicellular  organisms,  such 
as  paramoecium  or  amoeba,  death  cannot  be  regarded  as  a  natural 
process.  They  may  be  eaten  by  higher  organisms  or  serve  as  food  to 
vegetable  parasites,  but  so  long  as  conditions  are  favourable  and  food- 
supply  sufficient,  they  will  continue  to  grow  and  reproduce  them- 
selves eternally.  In  the  course  of  its  existence  each  individual  may  be 
brought  under  many  varieties  of  conditions  ;  some  of  these  may  be 
so  harmful  that  the  individual  is  destroyed  and  its  race  comes  to  an 
end.  Other  individuals,  under  circumstances  of  less  severity,  may 
undergo  modifications  in  their  molecular  structure  which  will  serve  to 
neutralise  the  effect  of  the  injurious  environment.  Any  such  modifica- 
tion in  structure,  morphological  or  molecular,  must  be  transmitted  to 
the  next  generation,  so  that  with  slowly  varying  external  conditions 
there  is  a  possibility  of  a  corresponding  slow  variation  in  type,  which 
may  finally  attain  a  form  altogether  different  from  that  with  which 
it  set  out.  A  new  species  may  in  this  way  be  formed  by  gradual 
alteration  of  environment.  It  is  not  therefore  difficult  to  understand 
in  the  case  of  such  organisms  either  the  maintenance  of  type  by  heredity 
under  constant  conditions,  or  the  change  of  type  with  gradually 
varying  conditions. 

Reproduction  by  continuous  growth  and  division  is  not,  however, 
the  only  means,  even  in  the  unicellular  animals,  by  which  new  genera- 
tions may  be  produced.  If  protozoa,  such  as  paramoecia,  be  kept  for 
a  long  time  in  nutrient  solutions  their  rapidity  of  reproduction  after  a 
time  falls  off,  while  many  die,  and  others  become  the  easy  prey  to 
infectious  diseases.  Under  these  conditions  a  new  phenomenon  makes 
its  appearance,  viz.  '  conjugation,'  which  is  the  analogue  of  the  sexual 
reproduction  of  the  higher  animals.  Infusoria  contain  two  kinds  of 
nuclei,  a  large  and  a  small,  known  as  the  macro-nucleus  and  the  micro- 
nucleus  respectively.  During  conjugation  the  macro-nucleus  breaks 
up  and  disappears  in  two  cells,  which  become  closely  applied  together, 
while  in  each  the  micro-nucleus  divides  twice  to  form  four  spindle- 
shaped  bodies.  Three  of  these  degenerate  (like  the  polar  bodies  of 
the  ovum),  while  the  fourth  divides  into  two.    This  is  followed  by  an 


ESSENTIAL  FEATURES  OF  SEXUAL  PROCESS       1343 

exchanfi^e  of  micro- jiuclei,  one  micro-jiucleus  from  a  passinji  into  b, 
while  one  micro-nucleiiK  from  u  passes  into  a.  The  two  cells  then 
separate,  a  single  micro-nucleus  being  formed  in  each  by  the  amalga- 
mation of  the  two.  Tliis  micro-nucleus  then  divides  three  times,  so 
that  eight  nuclei  are  formed,  wliile  the  cell  itself  divides  into  four,  two 
nuclei  passing  into  each  of  the  daughter  cells.     Of  these  one  enlarges 


Second  ib.tioii 


First  fission,  after  separation 

DiCfcrentiation   of  micro-  and 
macro-nuclei 


Separation  of  the  gamct«s 

>  l)i\islon     of     tlie     cleavage- 
nucleus 


Cleavage-nucleus 

Exchange   and  fusion   of   the 

perm-nuclei 
Gcrni-nuclci 


■  l-'tirniation  of  the  polar  bodies 


Union  of  the  gametes 


I'lG.  551.     Diagram   sliowini;  the  history  of  the    micro-nuclei    during  the 

conjugation  of  paramcecium.     (From  Wilson  after  Maup.\s.) 

X  and  Y  represent  the  opposed  macro-  and  micro-nuclei  in  the  two  gametes  ; 

circles  represent  degenerating  and  black  dots  persisting  nuclei. 

to  form  the  macro-nucleus,  while  the  other  remains  as  the  micro-nucleus. 
After  conjugation  has  occurred,  the  colony  of  infusoria  takes  on,  so 
to  speak,  a  new  lease  of  life,  and  there  is  a  rapid  production  of  new 
generations  by  simple  division  of  the  cells,  in  which  both  macro- 
nucleus  and  micro-nucleus  take  part.  Conjugation  apparently  only 
occurs  in  the  presence  of  adverse  conditions,  and  may  be  prevented 
almost  indefinitely  by  maintaining  the  colonies  in  as  favourable  condi- 
tions as  possible.  In  certain  organisms,  especially  in  Algjn,  in  which 
similar  })henomena  take  place,  each  organism  after  conjugation  may 
surround  itself  with  a  thickened  wall  and  remain  for  a  considerable 
length  of  time  in  a  state  of  sus])ended  animation.  It  is  very  difficult 
to  understand  the  advantage  of  this  interchange  of  nuclear  material 


1344  PHYSIOLOGY 

either  to  the  individual  or  to  the  race.  It  has  been  suggested  that 
as  soon  as  each  individual  concerned  in  the  process  receives  the  nuclear 
material  from  organisms  which  may  have  been  exposed  to  slightly 
different  circumstances,  corresponding  changes  will  be  introduced  into 
the  tendencies  to  growth  of  the  product  of  the  union.  Some  of  these 
tendencies  may  be  more  advantageous  than  before,  while  others  may 
be  the  reverse.  Increased  possibility  of  variation  is,  however,  intro- 
duced by  this  admixture  of  nuclear  material,  and-  this  may  be  the 
advantage  of  the  process  to  the  race.  It  should  be  noted  that  the  half 
of  the  nucleus  lost  by  each  conjugating  organism  is  qualitatively 
different  from  that  which  it  retains  and  probably  from  that  which  it 
receives.  A  generation  in  which  the  nucleus  can  be  represented  by 
ah,  and  which  by  simple  division  will  produce  similar  organisms  with 
nucleus  ah,  conjugates  with  an  organism  of  slightly  different  structure, 
and  therefore  with  a  nucleus  which  can  be  represented  as  cd.  After 
conjugation,  the  ah  generation  will  contain  a  nucleus  represented  by 
ac,  while  the  cd  generation  will  contain  a  nucleus  represented  by  hd. 
ac  or  hd  may  be  better  or  worse  combinations  than  ah  or  cd.  If  either 
of  them  is  better,  that  organism  will  survive  under  the  less  favourable 
conditions,  and  the  race  will  continue  with  a  slight,  and  to  us  inappre- 
ciable, change  of  type. 

.  REPRODUCTION  IN  THE  METAZOA 
The  numberless  cells  forming  the  bodies  of  the  higher  animals  are 
all  produced  by  a  series  of  divisions  from  a  single  cell,  the  fertilised 
ovum.  This  cell  is  the  result  of  a  process  of  conjugation  between  two 
cells  derived  from  different  individuals.  With  the  multiphcation  of 
cells  forming  a  single  organism  there  is  of  course  an  increased  size  of 
the  organism.  It  is  doubtful  whether  this  of  itself  would  be  of  any 
advantage,  were  it  not  that  the  multiplication  of  cells  goes  hand  in 
hand  with  differentiation,  groups  of  cells  being  modified  structurally 
and  set  aside  for  one  or  other  function  of  the  body.  Differentiation 
of  function  implies  higher  functional  capacity.  As  a  motor  organ  or 
as  a  means  of  locomotion,  the  differentiated  muscle-cells,  with  their 
attached  parts,  must  be  more  effective  than  the  undifferentiated 
protoplasm  of  the  amoeba.  Specialisation  of  function  involves  changes 
of  type  in  the  cells  resulting  fr-om  the  division  of  the  primitive 
undifferentiated  ovum.  In  most  cases  this  change  of  type  is  perma- 
nent. An  epithelial  cell  such  as  that  forming  the  epidermis  or 
the  liver,  when  it  divides,  produces  another  cell  of  the  same  kind. 
One  might  almost  speak  of  the  evolution  of  a  new  species  of  cell  but 
that  it  takes  place  within  the  short  period  of  the  development  of  the 
multicellular  individual,  instead  of  occupying  a  long  space  of  time, 
and  involving  the  destruction  of  countless  individuals,  as  is  the  case 


ESSENTIAL  FEATURES  OF  SEXUAL  PROCESS       134r, 

when  a  change  of  type  ^aadually  occurs  in  unicellular  organisms. 
Differentiation  necessarily  brink's  with  it  a  limitation  of  the  powers  of 
reproduction.  Any  one  of  the  descendants  of  a  unicellular  orj^anism 
is  in  ail  respects  equivalent  to  its  ancestor,  and  can  reproduce  the 
same  tvpe  of  individual.  The  specialised  liver-  or  muscle-cell  can 
only  produce  a  cell  of  the  san^e  type,  one.  that  is  tf)  say,  incapable 


Fig.  .").")2.  Origin  of  the  priiiKiniiiil  girm-Ci.'ll.s  and  ca.sting  out  <if  ihroiiiatin  in 
tliu  somatic  (ills  of  Afcitn'.s.  (WlLsox  after  Bovkki.) 
A,  two-cell  stage  dividing;  s,  stem-cell,  from  wliich  arise  the  germ-cells. 
B,  the  same  from  the  ,-ide,  later  in  the  second  cleavage,  showing  the  two  typ's 
of  mitosis  and  the  casting  out  of  chromatin  (c)  in  the  somatic  cell,  c,  resulting 
four-cell  stage  ;  the  eliminated  cliromatin  at  c.  D,  the  tliird  cleavage,  repeat- 
ing the  foregoing  process  in  tlie  two  U])per  cells. 

of  independent  existence  or  of  formint;  the  diverj^'ent  series  ol  types 
necessary  for  the  formation  of  an  individual.  DilYerentiation  of 
function  therefore  involves  the  settinif  aside  of  certain  cells,  (jerm- 
cells,  which  retain  their  primitive  character  and  are  capable  of 
iiulefinite  division  to  form  new  jfenerations  each  capable  of  developing 
into  a  complete  individual.  These  germ-cells  can  often  be  recognised 
from  tlie  very  earliest  divisions  of  the  fertilised  ovum,  which  lead  to 
the  produi'tion  of  the  mature  individual.  Thus,  in  Ascaris,  the  pro- 
genitor of  the  germ-cells  differs  from  the  somatic  cells  both  by  the 
greater  size  of  its  nii<leiis  and  in  its  mode  of  division  (Fit;.  ')')2).    Li  the 

85 


1346  PHYSIOLOGY 

cells  destined  to  produce  the  somatic  cells  a  portion  of  the  chromatin 
is  cast  out  into  the  cytoplasra,  where  it  degenerates,  so  that  only  in 
the  germ-cells  is  the  sum  total  of  the  chromatin  retained.  Thus  in 
the  two-celled  stage,  in  one  cell  all  the  chromatin  is  preserved,  while 
in  the  other  cell  the  thickened  ends  of  the  chromosomes  are  cast  off 
into  the  cytoplasm  and  degenerate,  only  the  thinner  central  portions 
being  preserved.  When  these  divide  again,  the  same  process  is 
repeated  in  only  one  of  the  daughter  cells  derived  from  a  germ-cell,  and 
the  process  is  repeated  during  five  or  six  divisions,  after  which  the 
chromatin  elimination  ceases,  and  the  two  primordial  germ-cells 
thenceforward  give  rise  only  to  other  germ-cells  in  which  the  entire 
chromatin  is  preserved.  Thus  "  the  original  nuclear  constitution  of  the 
fertilised  egg  is  transmitted,  as  if  by  a  law  of  primogeniture,  only  to 
one  daughter  cell,  and  by  this  again  to  one,  and  so  on,  while  in  other 
daughter  cells  the  chromatin  in  part  degenerates,  in  part  is  transformed, 
so  that  all  of  the  descendants  of  these  side-branches  receive  small 
reduced  nuclei  "  (Boveri,  quoted  by  Wilson). 

The  immortality,  which  was  the  property  of  all  the  unicellular 
ancestors  of  the  metazoa,  has  in  the  latter  descended  only  to  the  germ- 
cells.  All  the  other  cells  of  the  body,  which  form  the  nervous  and 
muscular  tissues,  glands,  skin,  &c.,  are  mortal.  They  pass  through 
a  certain  number  of  divisions  ;  but  although  this  number  is  large,  it  is 
limited,  and  on  the  number  of  divisions  which  are  possible  depends  the 
normal  duration  of  life  of  the  organism  to  which  the  cells  belong.  We 
may  thus  regard  the  egg-cell  as  dividing  into  two  parts.  From  one 
part  will  be  formed  by  differentiation  all  the  complex  somatic  mech- 
anisms of  the  adult  animal ;  the  other  part  will  divide,  but  will  remain 
in  an  im differentiated  form,  until  its  descendants  can  conjugate  with 
germ-cells  from  other  individuals  and  form  fertilised  egg-cells,  destined 
to  undergo  the  same  series  of  changes. 

The  metazoan  individual  thus  consists  of  a  mortal  host  holding  within 
itself  the  immortal  sexual  cells  or  gonads.  Gaskell  has  pointed  out  that  the 
development  of  the  fertiUsed  ovum  involves  two  parallel  processes — on  the  one 
hand,  the  elaboration  of  the  elements  forming  the  host  ;  on  the  other,  of  those 
derived  from  the  free-hving  independent  germ-cells.  From  the  very  beginning 
the  somatic  part  of  the  organism,  the  host,  is  a  reacting  individual  in  which 
the  nervous  system  acts  as  the  integrator  of  all  the  activities  of  the  body  and 
as  the  middleman  between  the  internal  and  external  epithehal  surfaces  and  the 
muscular  system.  The  host  may  thus  be  regarded  as  a  neuro-epithehal  syn- 
cj'tium,  every  step  in  its  evolution  and  differentiation  being  attended  by 
increased  control  of  all  the  units  by  a  central  nervous  system. 

The  gonads  were  placed  at  first  within  the  interstices  of  this  syncj'tium,  and 
escaped  to  form  a  new  generation  only  after  the  death  and  disintegration  of  the 
host.  But  differentiation  and  division  of  labour  affect  also  the  free-hving  gonads. 
Some  of  these  form  a  germ  epithehiim  surrounding  the  body  cavity,  of  which 
a  few  only  of  the  elemente  pass  out  of  the  host  as  perfect  germ-cells,  while  the 


ESSENTIAL  FEATURES  OF  SEXUAL  PROCESS       L347 

others  are  subordinated  to  the  metaboho  needs  of  these  germ-cells  and  are 
transformed  into  various  elements,  such  as  nurse-cells,  wandering  mesoderm 
cells  or  phagocytes,  yolk-cells,  and  so  one.  Gaskell  regards  the  greater  part, 
if  not  the  whole,  of  the  connective-tissue  framework  of  the  body,  as  well  as 
the  wandering  corpuscles  of  the  blood  and  tissue-fluicL*,  as  derived  from  these 
primitive  germ-ceUs.  All  these  tissues,  though  useful  to  the  host  as  well  as 
to  the  finally  successful  germ-cells,  present  the  common  feature  of  an  absolute 
independence  of  the  central  nervous  system.  Thus  the  evolution  of  the  animal 
kingdom  means  essentially  the  evolution  of  the  host,  and  must  therefore  be 
closely  connected  ^^^th  the  evolution  of  the  central  nervous  system,  the  ruling 
element  in  the  nexu:o -muscular  syncytium.  On  these  grounds  Gaskell  has  used 
the  comparative  morphology  of  the  central  nervous  system  as  a  means  of  tracing 
the  origin  of  the  vertebrate  from  the  invertebrate  type,  and  has  come  to  the 
conclusion  that  the  immediate  ancestor  of  the  vertebrate  must  be  sought  in 
the  invertebrate  group  presenting  the  most  highly  developed  central  nervous 
system,  namely,  the  arthropoda. 

The  whole  of  the  complex  mechanisms  which  are  concerned  in 
maintaining  the  life  of  the  individual  have  apparently  been  developed 
in  order  to  give  the  potentially  immortal  germ-cells  a  better  chance 
of  survival  in  the  struggle  for  existence.  From  the  broad  biological 
standpoint,  as  Foster  points  out,  all  the  toil  and  turmoil  of  human 
existence  may  be  regarded  simply  as  the  by-play  of  an  ox-um-bearing 
organism.  From  the  same  standpoint  one  must  acknowledge  that 
the  mortality  of  the  individual,  resulting  from  the  absence  of  an 
indefinite  power  of  multiplication  among  the  somatic  cells,  must  be 
an  advantage  to  the  race.  Throughout  the  li\nng  world  the  welfare 
of  the  individual  is  subordinated  to  that  of  the  species.  With  each  new 
generation  there  are  possibilities  of  variation  and  of  the  production 
of  individuals  better  or  worse  fitted  for  the  maintenance  of  the  race 
than  those  of  the  previous  generation.  Immortality  of  the  indi- 
vidual would  handicap  the  surN-ival  of  the  younger  generations,  and  we 
should  have  the  same  retardation  of  progress  in  a  race  that  we  see 
in  many  civilised  communities,  where  the  power  and  the  conduct  of 
affairs  are  in  the  hands  of  the  older  members. 

THE  FORMATION  OF  GERM-CELLS 
In  multicellular  organisms  the  cells  which  conjugate  to  form  a  new 
cell,  capable  of  developing  into  an  individual,  are  of  two  kinds.  One, 
which  has  generally  a  certain  amount  of  reserve  material  stored  up  in 
its  cytoplasm,  is  the  female  element  and  is  called  the  ovum.  The  other 
cell,  which  consists  of  little  more  than  nuclear  material,  is  the  male 
element  and  is  called  the  spermatozoon.  Both  kinds  of  cells  are 
derived  from  a  mass  of  undifferentiated  cells,  the  germ  epithelium, 
which,  as  we  have  seen,  can  often  be  traced  directly  back  to  the  first 
divisions  of  the  fertilised  egg.  The  use  of  the  reserve  material  in  the 
ovum  is  to  serve  as  food  for  the  developing  individual.     The  o\'um 


1348  PHYSIOLOGY 

and  spermatozoon  cannot  be  regarded  as  corresponding  to  complete 
cells.  Before  their  union  or  conjugation  both  male  and  female  germ- 
cells  undergo  certain  important  changes  which  differentiate  them 
from  the  ordinary  somatic  cells  of  the  individual.  The  essential 
differences  between  a  germ-cell  and  a  somatic  cell  can  be  best  seen  by  a 
study  of  the  nuclear  changes  which  precede  their  formation.  In  divi- 
sion the  nuclei  of  all  somatic  cells,  whether  of  plants  or  animals,  undergo 
a  series  of  changes  which,  in  their  broad  outlines,  are  identical  through- 
out both  animal  and  vegetable  kingdoms  (Fig.  553).  The  nucleus  of 
the  resting  cell  in  its  vegetative  condition  is  generally  separated  from 
the  cytoplasm  by  a  nuclear  membrane,  and  contains  irregular  masses 
of  a  material  staining  deeply  with  basic  dyes,  and  known  as  chromatin. 
In  the  cytoplasm  of  most  animal  cells  may  be  seen  a  small  particle 
known  as  the  centrosome.  When  division  is  about  to  take  place  the 
clumps  of  chromatin  arrange  themselves  into  a  filament  which  forms 
a  continuous  skein,  the  '  spireme  stage.'  This  then  breaks  up  into 
a  number  of  segments,  often  V-shaped,  the  chromatin  filaments  or 
chromosomes.  Each  of  the  filaments,  in  large  nuclei,  may  often  be 
seen  to  be  composed  of  rows  of  granules.  While  this  change  has  been 
occurring  the  nuclear  membrane  in  most  cases  disappears,  and  the 
centrosome  outside  the  nucleus  divides  into  two  parts,  which  travel 
to  opposite  ends  of  the  nucleus.  Round  each  centrosome  the  cyto- 
plasm is  modified  and  presents  a  radiate  appearance,  the  aster,  while 
joining  the  two  centrosomes  is  a  spindle  of  fine  fibres,  the  achromatic 
spindle.  The  V-shaped  segments  of  chromatin  arrange  themselves 
in  a  circle  at  the  equator  of  the  spindle  midway  between  the  two 
centrosomes.  Each  of  the  loops  then  splits  longitudinally,  and  each 
half  travels  towards  one  or  other  of  the  centrosomes,  thus  forming 
two  daughter  nuclei.  The  half -loops  then  join  to  form  a  skein,  and 
may  return  to  the  form  of  a  resting  nucleus.  These  different  phases 
in  division  are  presented  by  all  somatic  cells,  and  have  received  the 
following  names  : 

(1)  Prophase  (the  formation  of  the  spireme  and  of  the  achromatic 
spindle,  and  the  breaking  up  of  the  spireme  into  chromatin  loops  or 
chromosomes). 

(2)  Metaphase  (the  splitting  of  the  chromosomes). 

(3)  Anaphase  (the  travelling  of  each  half-chromosome  to  the 
extremity  of  the  spindle). 

(4)  Telophase  (the  retrogressive  changes  leading  to  the  conversion 
of  the  chromatin  filaments  into  an  ordinary  resting  nucleus,  which  are 
accompanied  or  preceded  by  a  division  of  the  cytoplasm  across  the 
equatorial  part  of  the  spindle). 

When  the  spireme  has  broken  up  into  separate  chromatin  loops,  it  is 
possible  to  count  them,  and  it  is  found  that  the  number  present  in 


ESSENTIAL  FEATURES  OF  SEXUAL  PROCESS  1349 
any  cell  is  constant  for  the  species.  Thus  every  human  somatic  cell 
has  sixteen  chromosomes  in  its  nucleus.  The  sanu-  number  is  found 
in  types  so  far  apart  as  the  ox,  the  guinea-pig,  and  the  oukmi.     in  tue 


1h\- 


MlA 


'^^ 


k^-^- 


KiG    -,.-,:}       ))nr.n.n.  slM-win-  tlu-  .ham.,,  which  <.c-c»r  in  the;  ccntrosomos 

and  nucleus  of  a  cell  in  the  process  of  mitotic  clivLsion.     (bciiAKEB.) 

The  nucleus  is  supposed  to  have  four  .lin.ninsnincs. 

mouse,  the  salamander,^  and  the  lily  the  number  is  twenty-four. 
Other  tvix's.  such  as  the  crustacean  Artemia,  are  said  to  have  as  many 
as  U)8  chromosomes,  while  in  Ascaris  the  cells  only  contain  two  or 
four  chromosomes.     All  these  changes,  which  are  included  under  the 


1350 


PHYSIOLOGY 


term  mitosis  or  haryohinesis,  seem  to  be  adapted  to  insuring  an  equal 
qualitative  as  well  as  quantitative  distribution  of  the  nuclear  chroma- 
tin among  the  daughter  cells  resulting  from  the  division  of  any  cell. 
As  we  have  seen  in  an  earlier  chapter,  the  nucleus,  by  its  interaction 
with  the  cytoplasm,  determines  the  processes  of  assimilation  and 
growth  of  the  whole  cell.  For  the  preservation  of  type  in  cell  division 
it  is  therefore  essential  that  the  nuclei  of  the  daughter  cells  shall  be 
identical  in  all  respects  with  the  nucleus  of  the  mother  cell. 

Sexual  reproduction  involves  the  conjugation  of  two  cells,  with 
union  of  their  nuclei.     If  each  of  these  nuclei  consisted  of  the  normal 


iWM 


V 


Fig.  554.     Three  stages  of  heterotype  mitosis  in  spermatocyte  of  triton. 

(Moore.) 
a,  geminal  condition  of  chromosomes  ;    h,  gemini  arranged  in  quadrate 
loops  or  tetrads  ;  c,  separation  of  tetrads  into  the  duplex  chromosomes  of  the 
daughter  nuclei. 


number  of  chromosomes,  the  fertihsed  egg-cell  would  contain  double 
the  number  characteristic  of  the  species,  and  since  these  chromo- 
somes would  divide  by  spHtting,  the  number  of  chromosomes  in  each 
cell  would  be  doubled  with  each  generation.  This  doubling  is  obviated 
by  the  fact  that,  in  the  formation  of  the  germ-cells,  the  ovum  and 
spermatozoon  nuclei  undergo  a  special  type  of  division,  which  leads 
to  the  reduction  of  the  chromosomes  in  the  sexually  mature  cell  to  one 
half  of  the  number  characteristic  of  the  species.  This  mode  of  cell 
division  is  often  called  '  division  by  reduction,'  or  '  heterotype  '  mitosis, 
or  '  meiosis  '  (Fig.  554).  We  may  take  as  an  example  the  development  of 
spermatozoa.  The  mother  cells  of  the  spermatozoa,  the  spermatocytes, 
divide  twice,  giving  rise  to  four  daughter  cells,  the  spermatids,  each  of 


ESSENTIAL  FEATURES  OF  SEXUAL  PROCESS       L351 

which  develops  into  a  functional  spermatozoon.  In  the  nuclear 
changes  preparatory  to  the  first  division,  the  spireme,  when  it  breaks 
up,  gives  rise  to  only  half  the  normal  number  of  chromosomes.  Thus 
if  the  somatic  number  of  chromosomes  were  four  we  should  find  in  the 
spermatocyte,  after  the  breaking  up  of  the  spireme,  only  two  chromo- 
somes. These  take  up  their  position  at  the  equator  of  the  achromatic 
spindle  and  then  divide,  but  the  division  is  effected,  not  by  splitting 
of  the  double  chromosome,  but  by  transverse  division.  Each  chromo- 
some breaks  into  half,  one  half  going  to  each  daughter  cell.  Since 
each  of  the  reduced  number  of  chromosomes  can  be  regarded  as 
made  up  of  two  normal  chromosomes   placed  end  to  end  or  joined 

Primordial  gcrm-rell. 


Spermatogonia. 


Primary  spermatocyte 
Secondary  spermatocytes. 

Spermatids. 
Spermatozoa. 


Division-period  fthe  number  of  divi- 
sions is  much  greater} . 


Growth-period. 


•  Maturation-period, 


Pig.  555. 


to  form  a  ring,  as  in  Fig.  55-1,  b,  the  division  in  the  middle  pro- 
vides for  a  qualitative  difference  between  the  two  daughter  cells. 
If  we  indicate  the  four  normal  chromosomes  as  a,  b,  c,  d,  in  ordi- 
nary somatic  division  each  daughter  cell  will  also  contain  chromo- 
somes which  may  be  represented  as  al,  61,  cl,  dl,  and  a2,  b2,  c2,  d2. 
In  the  spermatocyte  the  two  chromosomes  may  be  represented  as 
ab  and  cd.  When  they  divide  one  daughter  cell  receives  a  and  c, 
while  the  other  daughter  cell  receives  6  and  d.  The  second  division 
of  these  daughter  cells  takes  place  generally  by  splitting  of  the  filaments, 
so  that  finally  four  spermatids  are  produced  (Fig.  odij),  each  containing 
two  chromosomes,  two  of  them  containing  a  and  c,  while  the  other  two 
contain  b  and  d.  In  the  o\^um,  during  maturation,  analogous  change? 
take  place.  Two  successive  cell  divisions  occur  as  in  the  fornxation  of 
spermatozoa,  but  the  daughter  cells  are  of  very  unequal  size.  In  the 
first  division,  the  heterotypical  division,  the  chromosomes  fuse  in 


1352 


PHYSIOLOGY 


pairs  and  then  divide  as  in  the  spermatocytes,  so  that  each  of  the 
daughter  cells  contains  one  half  the  somatic  number  of  chromosomes. 
The  larger  of  the  two  resulting  cells,  which  retains  most  of  the  cyto- 
plasm, is  still  called  the  ovum,  while  the  smaller  one  is  spoken 
of  as  the  '  first  polar  body.'  The  ovum  now  divides  agaixi  and 
throws  off  a  second  polar  body,  the  division  being  of  the  homo- 
typical  variety.  The  first  polar  body  may  also  divide,  so  that  from  the 
original  ovum  three  cells  are  produced,  one  of  which  retains  the  greater 
part  of  the  cytoplasm,  while  the  others  are  extruded,  and  degenerate 
(Fig.  556).  The  mature  o^^.lm  has,  however,  only  half  the  normal 
number  of  chromosomes,  so  that  its  nucleus  is  equivalent  to  the  nucleus 

primordial  germ-cell. 


Oogonia. 


Primary  oocyte  or  ovarian  egg. 

SecondarV  oocytes  (egg  and 

first  polar  body) 


Mature  egg  and  three  polai  bodies 


Division-period  (the  niimVier  of  divi- 
sions is  much  greater). 


Growth-period. 


.   Maturation-period. 


Fig.  556. 


forming  the  head  of  the  spermatozoon.  The  only  difference  therefore 
between  the  formatioji  of  ovum  and  spermatozoon  is  that  in  the  former 
case  three  of  the  cells  formed  by  the  division  of  the  primitive  ovum  are 
abortive,  whereas  in  the  spermatozoon  all  four  daughter  cells  pro- 
duced from  the  spermatocyte  remain  functional.  The  production  of 
these  two  kinds  of  sexual  cell  is  represented  in  Figs.  555  and  556. 

Since  the  nuclei  of  the  mature  ovum  and  spermatozoon  only  contain 
half  the  normal  number  of  chromosomes,  they  are  generally  spoken  of 
as  pro-nuclei. 

FERTILISATION 
The  essential  features  of  fertilisation,  i.e.  the  union  of  the  sexual 
cells,  are  best  studied  in  some  of  the  lower  invertebrates,  such  as 
ascaris  or  echinoderms.  In  the  latter  fertihsation  takes  place  in  the 
sea-water,  into  which  both  ova  and  spermatozoa  are  extruded.  The 
ovum  of  the  echinoderm  consists  of  a  naked  marjri  of  protoplasm.     Of 


ESSENTIAL  FEATURES  OF  SEXUAL  PROCESS       L353 

the  countless  hordes  of  spermatozoa  which  may  be  in  the  neighbour- 
hood of  a  given  ovum  ojily  one  as  a  rule  enters.  As  soon  as  the  sperma- 
tozoon has  entered  the  ovum  a  tough  membrane  is  rapidly  formed  round 
the  latter,  so  preventing  the  entrance  of  any  further  spermatozoa. 
The  head  of  the  spermatozoon  enters  the  egg,  while  the  tail  atrophies 
and  disappears.  The  head  of  the  spermatozoon  enlarges  and  assumes 
the  character  of  a  nucleus,  the  dense  mass  of  chromatin  breaking  up 
first  into  a  thread  and  then  into  the  characteristic  number  of  chromo- 
somes (Fig.  557).  The  egg  now  contains  two  nuclei  or  pro-nuclei,  exactly 
similar  in  appearance,  one  derived  from  the  male  and  the  other  belong- 
ing to  the  egg  itself.  The  two  nuclei  approach  one  another  and  join.  In 
many  cases  there  is  an  apparent  fusion  of  the  substance  of  the  two 
nuclei.  In  others  the  chromatin  filaments  of  male  and  female  simply  lie 
side  by  side,  forming  a  complete  nucleus  with  the  somatic  number  of 
chromosomes.  Fertilisation  is  rapidly  folio  wed  by  cell  division.  Each  of 
the  chromosomes  splits  longitudinally,  half  going  to  each  of  the  daughter 
cells,  and  this  process  is  repeated  throughout  the  succeeding  divisions 
which  result  in  the  formation  of  the  new  individual.  Thus  every 
cell  of  the  body  contains  a  nucleus  of  which  exactly  one  half  is  paternal 
and  the  other  maternal  in  origin.  In  ascaris  it  is  often  possible,  in 
the  first  few  divisions  of  the  fertilised  ovum,  to  distinguish  in  the 
daughter  nuclei  the  chromatin  filaments  derived  from  the  male  from 
those  derived  from  the  female. 

The  strong  impetus  to  cell  division  given  by  the  process  of  fertilisa- 
tion has  naturally  aroused  much  curiosity  as  to  its  intimate  character. 
It  might  be  thought  that  for  cell  division  to  take  place  a  normal 
number  of  chromosomes  is  essential.  As  against  this  explanation 
may  be  adduced  the  fact  that  in  many  animals  parthenogenesis  occurs. 
The  female  pro -nucleus  may,  under  certain  conditions  of  environment 
or  nutrition,  start  dividing  and  give  rise  to  an  embryo,  each  cell  of 
which  contains  only  half  the  normal  number  of  chromosomes.  In 
other  cases  of  parthenogenesis  only  one  polar  body  is  extruded,  or  the 
second  polar  body  joins  again  with  the  female  pro-nucleus.  In  either 
case  the  ovum  contains  a  nucleus,  with  a  normal  number  of  chromo- 
somes, which  divides  and  produces  an  indiNndual  resembling  that 
resulting  from  the  union  of  ovum  and  spermatozoon.  It  has  been 
suggested  that  the  impetus  to  division  is  given  by  the  entry  of  the 
spermatozoon  itself.  In  the  series  of  divisions  which  precede  the 
formation  of  the  female  pro-nucleus  the  centrosome  of  the  ovimi 
generally  disappears,  whereas,  in  the  formation  of  the  spermatozoon,  the 
centrosome  persists  and  forms  the  middle  part  of  the  spermatozoon. 
In  many  cases  the  centrosomes  divide  in  the  spermatozoon  itself,  so 
that  this  contains  two  centrosomes  when  it  enters  the  egg.  These 
two   centrosomes    then    become    tlu'    centres    of   attraction   spheres. 


1354 


PHYSIOLOGY 


They  diverge,  and  between  them  is  formed  an  achromatic  spindle,  along 
the  equator  of  which  the  chromatin  filaments  of  male  and  female  pro- 


FiG.  557.  Fertilisation  and  first  division  of  ovum  of  Ascaris  megalo- 
cephala.  (Slightly  modified  from  Boveri  and  Wilson.) 
A,  second  polar  globule  just  formed ;  the  head  of  the  spermatozoon  is 
becoming  changed  into  a  reticular  nucleus  (  ^  ),  which,  however,  shows 
distinctly  two  chromosomes  ;  just  above  it,  its  archoplasm  is  shown  :  the 
egg-nucleus  (  $  )  also  shows  two  chromosomes.  B,  both  pro-nuclei  are  now 
reticular  and  enlarged;  a  double  centrosome  (a)  is  visible  in  the  archoplasm 
which  lies  between  them,  c,  the  chromatin  in  each  nucleus  is  now  converted 
into  two  filamentous  chromosomes ;  the  centcosomes  are  separating  from 
one  another,  d,  the  chromosomes  are  more  distinct  and  shortened  ;  the 
nuclear  membranes  have  disappeared  ;  the  attraction-spheres  are  distinct. 
E,  mingling  and  splitting  of  the  four  chromosomes  (c) ;  the  achromatic 
spindle  is  fully  formed.  F,  separation  (towards  the  poles  of  the  spindle)  of  the 
halves  of  the  split  chromosomes,  and  commencing  division  of  the  cytoplasm. 
Each  of  the  daughter  cells  now  has  four  chromosomes  ;  two  of  these  have  been 
derived  from  the  ovum  nucleus,  two  from  the  spermatozoon  miclcus. 


nuclei  arrange  themselves.     It  is  doubtful,  however,  how  far  the  centro- 
some can  be  regarded  as  a  permanent  cell  structure.     In  echinoderm 


ESSENTIAL  FEATURES  OF  SEXUAL  PROCESS       L355 

eggs  various  modes  of  treatment  will  lead  to  the  appearance  of  attrac- 
tion spheres  in  the  cytoplasm,  and  even  to  division  of  the  non-fertib'sed 
egg.  Loeb  has  suggested  that  the  action  of  the  spermatozoon  is  essen- 
tially chemical  in  character.  By  alteration  of  the  mediimi  in  which 
the  eggs  are  contained,  Loeb  has  succeeded  in  imitating  exactly  the 
changes  which  normally  need  the  entrance  of  a  spermatozoon  for  their 
occurrence.  On  immersing  the  eggs  in  a  weak  solution  of  formic  or 
lactic  acid,  a  membrane  is  formed.  The  eggs  are  then  taken  from  the 
acid,  placed  in  concentrated  sea-water  for  a  short  time,  and  then 
removed  to  ordinary  sea-water.  Division  rapidly  occurs  with  the 
production  of  a  normal  larva.  He  suggests  that  the  spermatozoon 
brings  with  it  ferments,  or  other  chemical  substances,  which  excite  the 
egg-nucleus  and  cytoplasm  in  the  same  way  as  the  chemical  measures 
adopted  for  this  artificial  induction  of  segmentation. 


SECTION  II 

DEVELOPMENT  AND  HEREDITY 

There  is  perhaps  no  phenomenon  which  is  so  impressive  as  the 
development  from  a  minute  speck  of  protoplasm,  the  fertihsed  egg,  of 
an  individual  partaking  of  the  minutest  characteristics  of  both  its 
parents.  An  egg-cell  has  much  the  same  appearance  whether  it 
belong  to  an  echinoderm,  a  fish,  or  a  man.  In  the  process  of  develop- 
ment, by  a  simple  repetition  of  a  series  of  cell  divisions,  this  undif- 
ferentiated protoplasm  is  formed  into  the  complex  organs  with  the 
potentialities  and  habits  which  distinguish  the  tj^pe  from  which  the 
protoplasm  has  been  derived.  We  cannot  wonder  that  the  intimate 
nature  of  this  process  has  been  the  subject  of  speculation  from  the  very- 
birth  of  science.  Running  through  these  speculations  are  two  main 
ideas,  which  have  been  labelled  the  theories  of  '  evolution  '  and  of 
'  epigenesis.'  By  the  '  evolutionists  '  the  egg  was  believed  to  con- 
tain an  embryo  fully  formed  in  mmiature,  as  the  bud  contains  the 
flower  or  the  chrysalis  the  butterfly.  Development  was  therefore  only 
the  unfolding  of  something  already  existing.  If,  however,  this  theory 
be  pushed  to  its  utmost  and  if  the  egg  contain  a  complete  embryo,  this 
must  itself  contain  eggs  for  the  next  generation,  and  so  on  ad  infinitum, 
a  conclusion  which  is  of  course  absurd.  According  to  the  theory  of 
epigenesis,  the  structure  of  the  egg  is  wholly  different  from  that  of 
the  adult,  its  development  consisting  in  the  continual  formation  one 
after  the  other  of  new  parts  previously  non-existent  as  such.  There 
is  no  doubt  that  this  view  is  fundamentally  correct.  The  difficulty 
with  which  we  have  to  contend  is  the  understanding  of  the  orderly 
sequence  and  correlation  of  the  cell  divisions  and  differentiations 
which  result  in  an  adult  individual  of  the  same  type  as  the  parents. 
The  fact  that,  under  approximately  identical  conditions,  one  mam- 
malian ovum  will  give  rise  to  a  mouse  and  the  other  to  a  man  indicates 
that  there  must  be  some  difference  in  structure,  organisation,  or  com- 
position of  the  primitive  egg-cell  in  each  case,  and  the  theory  of '  evolu- 
tion '  has  reappeared  in  latter  days  in  a  somewhat  modified  form, 
according  to  which  the  differentiation  of  the  ovum  is  causally  con- 
nected with  a  preformed  differentiation  in  the  nuclear  structures,  e.g. 
chromosomes,  of  the  ovum  itself.  We  have  already  seen  that  the 
germ-cells  in  some  types  are  separated  off  from  the  rest  of  the  embryo 

1356 


DEVELOPMENT  AXD  HEREDITY  1857 

at  a  fairly  early  sta<i;e.  It"  in  the  two-celled  stage  of  the  frog's  egg  one 
cell  be  destroyed  by  means  of  a  hot  wire,  the  other  cell  develops  to 
form  half  an  embryo,  thus  suggesting  that  each  cell  of  the  two-celled 
embryo  could  give  rise  only  to  the  corresponding  half  of  the  body. 
This  limitation  of  development,  however,  only  occurs  if  the  intact  cell 
be  left  in  connection  with  the  cell  that  has  been  injured.  If,  in 
echinoderm  larva?,  the  cells  be  entirely  separated,  even  as  late  as  the 
eight-celled  stage  of  division,  each  cell  will  give  rise  to  a  whole  embryo, 
differing  from  a  normal  embryo  only  in  respect  of  size.  This  difference 
suggests  that  the  number  of  divisions  that  each  cell  can  undergo  is 
predetermined  in  the  egg-cell  itself,  but  shows  also  that  the  cells  into 
which  the  egg  divides  are,  at  first  at  any  rate,  equipotential.  We  must 
assume  therefore  that  the  reason  why  one  cell  under  ordinary  circum- 
stances only  forms  one  half  of  the  embryo  is  that  its  development  is 
regulated  and  determined  by  the  presence  of  the  other  cell  in  connec- 
tion with  it  forming  the  other  half  of  the  embryo.  That  is  to  say,  the 
development  of  the  egg  involves  the  reaction  to  environment  of  a 
protoplasm  of  certain  properties  and  powers  of  reaction.  The  final 
product  of  development  depends  (1)  on  the  nature  of  the  protoplasm 
(including  the  nucleus)  of  which  the  egg  is  composed,  and  (2)  on  the 
environmental  conditions  to  which  the  egg  is  subjected  during  the  rapid 
growth  and  multiplication  attending  its  development.  We  could 
therefore  speak  of  a  morphology  of  inheritance,  but  the  morphology 
would  be  ultra-microscopic  and  have  relation  to  the  molecular  structure 
of  the  protoplasm  of  which  the  egg  was  composed. 

In  the  transmission  of  the  potentialities  of  development  from 
parent  to  fertilised  egg  we  must  regard  the  nucleus  as  the  essential 
structure.  In  ordinary  development  the  spermatozoon  furnishes 
only  a  nucleus  and  centrosome,  the  ovum  supplying  the  whole  of  the 
cytoplasm.  There  seems,  however,  no  grounds  for  assigning  any 
directive  power  to  the  latter  structure.  In  echinoderm  ova  it  is 
possible  to  get  rid  of  the  nucleus  and  then  by  the  introduction  of 
spermatozoa  to  have  an  individual  entirely  paternal  in  origin,  which, 
on  development,  produces  a  larva  of  the  paternal  character.  In  division 
of  the  egg  the  only  part  of  the  cell  which  divides  so  that  each  daughter 
cell  shall  include  an  equal  part  of  both  parental  germs  is  the  nucleus. 
The  constant  number  of  the  chromosomes  in  each  species,  and  their 
accurate  division  on  mitosis,  suggest  that  the  hereditary  transmission 
of  the  potentialities  of  the  cell  is  bound  up  with  the  chromosomes. 
It  has  been  suggested  that  every  character  is  located  in  a  chromosome 
or  part  of  a  chromosome.  If  this  be  the  case  one  might  regard  the 
differentiation  into  various  tissues,  which  occurs  in  the  process  of 
development,  as  occasioned  by  an  actual  loss  or  degeneration  of  the 
constituent  parts  of  one  or  more  chromosomes.     There  is  no  doubt 


1358  PHYSIOLOGY 

that  many  tissues  do  become  thus  differentiated  at  a  fairly  early  period 
in  development,  having  undergone  in  the  process  an  absolute  modifica- 
tion of  their  potentialities,  which  must  be  at  any  rate  shared  by 
the  chromosomes  of  their  constituent  cells.  The  extent  to  which  this 
limitation  of  powers  of  development  occurs  varies  widely  in  different 
animals.  In  the  higher  animals,  such  as  man,  epithelium  will  reproduce 
epithelium,  and  liver-cells  will  reproduce  liver-cells,  while  nerve-cells 
are  absolutely  incapable  of  multiplication.  On  the  other  hand,  in 
Crustacea  a  whole  Umb  may  be  torn  off  and  be  regenerated  from  the 
tissues  of  the  stump.  Destruction  of  the  optic  lens  in  the  salamander 
is  followed  by  its  regeneration  from  the  anterior  part  of  the  optic  cup, 
a  tissue  which  had  no  part  in  its  primary  formation.  Worms  will  form 
a  new  head  after  decapitation.  In  these  animals  therefore  the  cells  in 
many  parts  of  the  body  possess  the  power  of  directed  growth,  if  need 
arise,  in  case  of  injury,  and  are  able  to  form  tissues  of  many  different 
kinds. 

I  have  mentioned  the  small  size  of  the  larva  formed  from  isolated 
cells  of  the  segmenting  egg  as  a  proof  that  the  number  of  cell  divisions 
of  the  somatic  part  of  the  developing  animal  is  predeternained  and 
limited.  This  conclusion  must  not  be  taken  too  absolutely.  Many  of 
the  tissues,  even  of  the  highest  animals,  possess  the  power  of  almost 
unlimited  regeneration  by  cell-multiplication  as  a  response  to  injury. 
Under  normal  conditions  the  growth  of  such  tissues  is  limited,  not 
by  absence  of  power  to  divide,  but  as  a  result  of  a  mutual  interaction 
between  them  and  the  surrounding  cells.  We  might  almost  speak  of  a 
struggle  for  existence  between  the  various  tissues  of  the  body,  which 
in  the  healthy  organism  results  in  an  equihbriimi,  or  balance  of  multi- 
plicative powers.  If  this  balance  is  upset  by  any  means,  such  as 
stimulation  of  certain  cells  by  the  presence  of  intra-cellular  parasites,  or 
their  destruction  by  irritants  or  other  abnormal  conditions  [e.g.  expo- 
sure to  X-rays),  one  tissue  may  enter  into  active  growth  at  the  expense 
of  the  surrounding  tissues,  and  the  result  is  a  morbid  growth  such  as 
cancer.  It  is  possible  that  in  the  latter  case  a  new  factor  comes  into 
play.  All  tissues  of  the  body,  as  we  have  seen,  begin  to  die  from  the 
time  that  they  are  born.  They  have  a  certain  span  of  Ufe,  a  certain 
hmitation  to  their  generations,  which  results  in  the  phenomenon  of 
senescence,  such  as  occurs  in  a  culture  of  protozoa.  In  protozoa  this 
phenomenon  is  the  signal  for  rejuvenation  by  conjugation.  It  is 
possible  that  in  cancer  something  of  the  same  nature  occurs.  It  is  at 
any  rate  significant  that  in  a  rapidly  growing  cancer  many  of  the 
dividing  cells  present  the  phenomenon  of  heterotype  mitosis,  a  pheno- 
menon which  is  otherwise  found  only  in  the  sexual  cells  preparing  for 
conjugation  and  for  the  production  of  a  new  individual.  Given 
adequate  conditions  of  nutrition,  there  seems  to  be  no  limit  to  the 


DEVELOPMENT  AND  HEREDITY  1359 

growth  of  cancer-cells.  In  mice  a  cancer  may  be  transfen-ed  from  one 
individual  to  another  by  inoculation,  and  this  process  nxay  apparently 
go  on  indefinitely,  so  that  finally  a  mass  of  cancer-cells  may  have 
been  produced  equal  in  volume  to  many  thousands  of  mice,  and  per- 
sisting long  after  the  mouse  from  which  it  was  fii-st  taken  would  have 
died  under  natural  conditions. 

In  sexual  reproduction  the  new  individual  partakes  of  charac- 
teristics of  both  its  parents.  It  therefore  resembles  neither  of  its 
parents  in  all  details.  The  conjugation  of  the  two  parent  cells  from 
which  it  is  derived  has  been  preceded  by  a  thro-wang  out  of  half  the 
chromosomes  from  each  parent  cell.  It  is  therefore  natural  to  ascribe 
the  variations  which  occur  among  the  members  of  one  family  to  a 
qualitative  difference  in  the  chromosomes  which  have  been  eliminated 
in  the  formation  of  their  respective  egg-cells.  Can  we  regard  the 
chromosomes  as  representing  separate  qualities  of  the  individual,  or 
must  we  assume  that  all  qualities  are  represented  to  a  greater  or  less 
extent  in  every  chromosome  ?  In  the  case  of  many  qualities,  especially 
those  which  distinguish  the  species  as  apart  from  the  individual  varia- 
tion or  family  characteristic,  we  must  probably  accept  the  latter  idea 
as  correct.  In  this  case  the  child  can  be  regarded  as  representing  an 
arithmetical  mean  of  both  its  parents.  In  certain  respects,  however, 
a  quality  seems  to  be  transmitted  from  parent  to  offspring  either  com- 
pletely or  not  at  all.  This  is  specially  applicable  to  those  characteristics 
which  have  been  rapidly  produced  by  artificial  selection,  characters 
which,  if  artificial  selection  be  abandoned,  rapidly  disappear,  with 
reversion  to  the  type  from  which  the  special  strain  was  ultimately 
produced.  The  way  in  which  these  characteristics  are  transmitted 
was  first  studied  by  Mendel  and  has  been  formulated  as  Mendel's  law. 
Mendel's  first  experiments  were  carried  out  on  peas.  On  crossing  a  tall 
plant  with  a  dwarf  plant  seeds  were  obtained  from  which  all  the  plants 
were  tall.  On  recrossing  the  plants  of  this  generation  among  one 
another  a  third  generation  was  obtained  in  which  25  per  cent,  of 
the  plants  were  dwarfs  and  75  per  cent,  were  tall.  Crossing  the  dwarf 
plants  among  themselves  led  to  the  production  of  dwarf  plants 
through  successive  generations.  Of  the  tall  plants  25  per  cent,  and 
all  their  descendants  continued  to  produce  tall  plants  when  self- 
fertilised,  whereas  of  the  remaining  50  per  cent,  of  the  tall  plants 
25  per  cent,  produced  dwarfs  and  the  remaining  75  per  cent,  produced 
tall  plants.  On  continuing  the  process  of  breeding,  the  dwarf  plants 
when  self -fertilised  always  produced  dwarfs,  whereas  of  the  tall  plants 
25  per  cent,  produced  tall  plants,  which  bred  true,  while  the  remain- 
ing 50  per  cent,  produced  the  sanu^  percentage  of  tall  and  dwarf  as  in 
the  preceding  generations.  Mendel  explained  these  results  by  the 
assumption  that  a  character  could  be  dominant  or  recessive.     If  both 


1360  PHYSIOLOGY 

characters  were  present  together  in  one  plant  it  would  partake  of  the 
dominant  type  ;  the  fact  that  this  plant  possessed  the  recessive 
character  would  only  be  shown  by  the  results  of  breeding.  In  the 
case  of  the  peas  the  tall  character  was  dominant  over  the  dwarf.  Thus 
when  the  tall  and  dwarf  pea  were  crossed  the  first  generation  of  plants 
would  exhibit  the  dominant  character  and  be  tall.  In  the  second 
generation,  however,  25  per  cent,  of  the  individuals  would  be  pure 
dominants  (D  +  D),  25  per  cent,  would  be  pure  recessive  (R  +  R), 
while  50  per  cent,  would  be  mixed  (D  +  R).  The  pure  dominants 
bred  together  would  always  give  rise  to  nothing  but  pure  dominants, 
the  recessive  to  recessive,  while  the  mixed  type  would  always,  as  before, 
give  rise  to  25  per  cent,  pure  dominants,  50  per  cent,  mixed,  and 
25  per  cent,  pure  recessives.  These  results  may  perhaps  be  made 
clearer  by  the  following  Table  : 

D  +  R 

DR 

\ 

25%  D  50%  DR  25%  R 

I \ "I 

D        25%  D  50%,  DR  25%  R  R 


D  D     25%  D     50%  DR  25%  R       R  R 

It  has  been  suggested  that  a  very  large  number,  if  not  all,  of  the 
characters  of  an  individual  might  be  brought  under  this  law.  This 
might  be  done  by  indefinitely  subdividing  the  characters,  but  the 
question  would  theii  become  beyond  the  limits  of  analysis  or  experi- 
mental investigation.  There  is  no  doubt  that  many  qualities  are 
subject  to  Mendel's  law,  and  that  their  study  will  be  of  considerable 
assistance  in  guiding  the  efforts  of  our  breeders  and  horticulturists  in 
the  formation  of  new  varieties  desirable  for  their  value  to  man.  In 
respect  of  many  qualities  the  Mendelian  law  seems  to  fail.  Thus  in 
man  the  progeny  of  a  cross  between  a  white  and  black  race  are  more  or 
less  intermediate  between  the  two  and  vary  according  to  the  amount  of 
black  and  white  blood  introduced  in  succeeding  generations.  Definite 
black  and  white  individuals  are  not  produced,  but  merely  individuals 
of  various  degrees  of  brownness. 


SECTION  in 
REPRODUCTION  IN  MAN 

THE  DEVELOPMENT  OF  THE  REPRODUCTIVE  ORGANS 

The  most  marked  example  of  chemical  correlation  is  found  by 
the  influence  exerted  by  the  genital  glands  upon  the  other  parts  of 
the  reproductive  apparatus  and  upon  the  body  generally.  Thus 
castration,  i.e.  removal  of  the  testes  or  ovaries,  if  carried  out  before 
the  time  of  puberty,  prevents  the  development  of  the  secondary 
sexual  characters,  which  normally  occurs  at  this  epoch  in  both  sexes. 
Puberty  denotes  the  period  at  which  ripe  spermatozoa  and  ova  are 
produced  in  the  testis  and  ovary  respectively.  In  the  human  species 
this  period  is  marked  or  preceded  in  the  male  by  increased  growth  of 
the  skeleton,  by  growth  of  the  larynx,  leading  to  a  lowering  in  pitch 
of  the  voice,  by  the  growth  of  hair  on  the  face  and  pubes,  and  by 
the  development  of  sexual  desire.  In  the  female  we  find  at  puberty 
enlargement  of  the  breasts,  attended  by  some  gro^^i:h  of  the  mammary 
glands  and  by  a  moulding  of  the  whole  form,  making  it  more  fit  for 
the  bearing  of  children.  The  chief  sign  of  puberty  in  the  female  con- 
sists in  the  periodic  changes  in  the  uterus,  which  give  rise  to  menstrua- 
tion, i.e.  a  flow  of  blood  and  mucus  from  the  genital  organs,  lasting 
three  to  five  days  and  repeated  every  four  weeks.  Menstruation  per- 
sists so  long  as  the  ovary  is  functional,  i.e.  is  producing  ripe  ova.  The 
activity  of  the  ovary  comes  to  an  end  between  the  forty-fifth  and 
fiftieth  year  ('  the  climacteric  '  or  '  change  of  life  ').  With  the  cessation 
of  its  activity  menstruation  also  stops,  and  the  uterus  undergoes  a 
process  of  atrophy.  These  secondary  sexual  characters  must  be 
ascribed  to  the  influence  of  chemical  substances  produced  in  the  ovary 
and  testis  respectively.  Castration  after  puberty,  though  not  causing 
any  change  in  the  skeleton,  which  has  already  assumed  its  permanent 
form,  brings  about  retrogressive  changes  in  the  other  genital  organs, 
analogous  to  those  occurring  in  the  female  at  the  climacteric.  In 
animals  the  phenomena  of  '  coming  on  heat  '  or  '  rut  '  seeni  to  be 
analogous  with  menstruation  in  the  human  female,  and  like  this 
depend  on  the  nornuil  activity  of  the  ovary.  They  are  pernumently 
abolished  by  extirpation  of  the  ovaries,  but  may  be  reinduced  by 
implantation  in  the  peritoneum  of  an  ovary  from  another  animal  of 
the  same  species.     This  fact  shows  that  the  changes  in  the  uterus 

1361  86 


1362  PHYSIOLOGY 

responsible  for  rut.  as  well  as  for  menstruation,  are  independent  of  any 
nervous  connections  between  the  ovaries  and  the  rest  of  the  body,  and 
must  therefore  be  brought  about  by  the  circulation  in  the  blood  of 
specific  chemical  substances  produced  in  the  ovaries.  According  to 
some  authors,  the  essential  factors  for  the  production  of  these  genital 
hormones  are  the  '  interstitial  cells  '  found  both  in  the  testes  and 
ovaries  of  various  animals.  These  interstitial  cells  are  not.  however, 
universally  present.  It  has  been  shown  that,  by  means  of  the  Rontgen 
rays,  it  is  possible  to  destroy  the  germ-cells  in  either  testes  or  ovaries,  so 
rendering  the  animal  sterile.  The  interstitial  cells,  when  present,  are 
not  destroyed  by  these  rays,  yet  the  effects  on  the  accessory  genital 
organs  are  stated  to  be  as  marked  as  after  complete  extirpation  of 
either  ovaries  or  testes. 

The  chemical  correlations  between  the  ovaries  and  the  other 
organs  concerned  in  reproduction  are  perhaps  best  marked  in  the 
changes  which  attend  pregnancy.  In  this  case  the  fertilisation  of  the 
ovum  by  a  spermatozoon  is  followed  by  a  great  development,  first  of 
the  mucous  membrane  and  later  on  of  the  muscular  wall  of  the  uterus. 
The  mucous  membrane  thickens,  apparently  in  order  to  form  a  bed  for 
the  developing  fertilised  ovum.  With  this  growth  of  the  uterus  there 
is  a  corresponding  growth  of  the  other  parts  of  the  genital  tract, 
e.g.  the  vagina.  At  the  same  time  rapid  changes  take  place  in  the 
mammary  glands.  These  changes  may  be  studied  experimentally  in 
the  rabbit,  in  which  animal  gestation  lasts  only  about  twenty-nine 
days.  In  a  virgin  rabbit  of  a  year  old  it  is  difficult  with  the  naked  eye 
to  see  any  trace  of  the  mammary  gland  in  the  tissue  lying  under  the 
nipples.  Each  gland  is  limited  to  an  area  not  more  than  1  cm.  broad, 
and  consists  entirely  of  ducts  lined  with  a  single  layer  of  flattened 
epithelial  cells.  With  the  occurrence  of  conception  a  marked  change 
takes  place.  Four  or  five  days  after  fertilisation,  when  it  is  still 
impossible  with  the  naked  eye  to  discover  any  embryos  in  the  swollen 
uterine  horns,  on  reflecting  the  skin  from  the  abdomen  each  mammary 
gland  appears  as  a  circular  pink  area,  about  3  cm.  in  diameter.  On 
section  the  gland  consists  of  ducts  which  are  in  an  active  state  of 
proliferation,  their  epithelial  lining  being  two  or  three  cells  thick  and 
presenting  numerous  mitotic  figures.  By  the  ninth  day  the  whole 
abdomen  is  covered  with  a  thin  layer  of  glandular  tissue  ;  by  the 
twenty-fifth  day  this  tissue  is  \  cm.  in  thickness  and  consists  for  the 
greater  part  of  secreting  alveoli,  lined  with  cells  containing  numerous 
fat -globules.     At  full  term  the  alveoli  contain  ready-formed  milk. 

This  hypertrophy  of  the  mammary  glands  occurs  during  pregnancy 
after  complete  division  of  all  possible  nervous  paths  between  the 
glands  of  the  ovaries  or  uterus.  In  the  guinea-pig  a  mammary  gland 
has  been  actually  transplanted  to  another  part  of  the  body,  thus 


REPRODUCTION  IN  MAN  1303 

severing  all  its  normal  nervous  connections,  and  yet  it  enlarged  as 
usual  during  a  subsequent  pregnancy.  It  has  been  shown  (Starling 
and  Lane-Claypon)  that  a  somewhat  similar  hypertrophy  may  be 
found  in  virgin  rabbits  after  the  injection  of  watery  extracts  made  from 
foetal  rabbits.  It  may  therefore  be  concluded  that  the  chief  factor  in 
exciting  the  growth  of  the  mammary  glands  during  pregnancy  is  some 
chemical  substance — a  hormone,  produced  in  the  foetus  and  trans- 
mitted through  the  placenta  to  the  maternal  blood-stream.  This 
fcetal  hormone  is  not  the  only  factor  involved  in  the  growi;h 
of  the  mammary  glands.  Ancel  and  Bouin  have  brought  forward 
evidence  that  the  corpus  luteum — ^the  tissue  produced  in  the  ovary  as 
a  result  of  the  discharge  of  an  ovum — is  intimately  concerned  with  the 
growth  of  the  mammary  glands,  and  may  indeed  cause  a  certain  degree 
of  hypertrophy  of  these  glands  in  the  entire  absence  of  any  product  of 
conception  within  the  uterus.*  The  limited  growth  of  the  glands,  which 
occurs  at  puberty,  can  certainly  not  be  ascribed  to  the  presence  of  a 
foetus  in  the  uterus,  and  must  be  connected  with  the  growth  of  ripe  ova, 
or,  as  suggested  by  the  two  French  authors,  with  the  growth  of  the 
tissue  of  the  corpus  luteum,  resulting  from  the  discharge  of  ova. 

There  seem  also  to  be  obscure  relationships  between  the  activity  of 
the  sexual  organs  and  that  of  certain  so-called  ductless  glands.  Thus 
castration  at  an  early  age  leads  to  persistence  of  the  thymus  gland, 
whereas  normally  this  gland  atrophies  just  before  the  sexual  organs 
commence  their  functional  activity.  The  existence  of  a  connection 
between  the  thyroid  and  the  ovaries  has  been  a  popular  belief  for  2000 
years.  In  many  individuals  the  thyroid  is  perceptibly  enlarged  at 
each  menstrual  period.  On  the  otlier  hand,  extirpation  of  the  th\Toid 
before  puberty  bring's  about,  among  the  other  signs  of  cretinism,  failure 
of  development  of  the  ovaries,  so  that  puberty  is  delayed  partially  or 
comj)letely. 

We  must  thus  regard  the  germ-cells  not  only  as  representing  the  cells 
from  which  the  individuals  of  the  new  generation  may  be  developed, 
but  also  as  concerned  in  the  formation  of  chemical  substances  which, 
discharged  into  their  hosts,  affect  many  or  all  of  the  functions  of  the 

*  According  to  Ancel  and  Bouin,  in  the  rabbit  discharge  of  an  ovum  and 
formation  of  a  corpus  luteum  only  occur  as  a  result  of  copulation.  The  same 
effect  may  be  pn^duced  by  artificial  rupture  of  a  ripe  follicle.  Whenever  this 
occurs  there  is  a  development  of  the  mammary  glands.  If  no  impregnation  has 
taken  place  {e.g.  if  the  buck  has  been  .sterilised  by  ligature  of  the  va.s  deferens), 
the  glands  develop  for  fourteen  days  and  then  begin  to  atrophy.  This  jH-riod 
corresponds  to  the  jx-riod  of  active  growtii  of  the  corpus  luteum.  The  continued 
growth  during  the  latter  iialf  of  ]»n'gnancy  these  authors  aserilK"  to  the  production 
of  another  hormone  by  a  siK'cial  glandular  tissue  (*  mytmu'trial  gland')  which 
makes  its  appearance  about  the  fourteenth  day  in  the  wall  of  the  uterus,  at  the 
site  of  implantation  of  the  placenta,  and  lasts  until  the  end  of  pregnancy. 


1364 


PHYSIOLOGY 


latter,  with  the  object  of  finally  subordinating  the  activities  of  the 
individual  to  the  preservation  and  perpetuation  of  the  species. 

THE  MALE   REPRODUCTIVE   ORGANS 

In   all  the  higher  animals  we  may  divide  the  reproductive  organs 

into  the  essential  organs,  which  form  the  germ-cells,  the  spermatozoa 

and  ova  respectively,  and  the  accessory  organs,  which  have  as  their 

office   the  facilitation   of   the  access  of   the  spermatozoa  to  the  ova 


Appendix 


Epididymis 


Tunica  vaginalis 

Tunica  albuginea 

Septum 

Seminal  tubules 

Lobule 
Mediastinum 

Testis 


~"    Vas  deferens 


Paradidymis 


Vasa  eflferentia 

Appendix  of  rete 

testis 

Vas  aberrans 


Lobule     Straight      Eete 
tubules        testis 

Fig.  558.     Diagrammatic  representation  of  the  course  of  the  seminal  tubules  in  the 
testis  and  epididymis.     (After  Nagel.) 

(fertilisation),  and  in  the  female  the  nutrition  of  the  product  of  ferti- 
lisation during  the  early  period  of  its  development. 

The  essential  sexual  organ  of  the  male  is  represented  by  the  testis. 
This  is  made  up  of  a  collection  of  convoluted  tubules,  the  seminal 
tubules,  which  are  contained  in  a  number  of  compartments  separated 
by  fibrous  septa.  The  tubules  present  few  or  no  branches,  each  one 
being  about  500  mm.  long.  The  testis  is  formed  in  the  first  mstance 
in  the  peritoneal  cavity  from  the  germinal  epithelium,  but  early  in 
life  leaves  the  abdominal  cavity  by  the  abdominal  ring  to  lie  in  a 
pouch  of  skin — the  scrotum.  Several  tubules  unite  to  form  a  straight 
tubule,  which  leads  by  a  series  of  communicating  spaces,  the  rete 
testis,  into  the  vasa  efferentia  (Fig.  558).  These  unite  to  form  the 
duct  of  the  epididymis,  which  forms  a  mass  lying  at  the  back  of 
the  testis.  The  epididymis  is  composed  of  the  convolutions  of 
this  single  duct,  which  is  about  20  feet  long.    From  the   lower   end 


REPRODUCTION  IN  MAN  1305 

of  the  epididymis  the  vas  deferens,  a  tube  with  thick  muscular 
walls,  leads  by  the  abdominal  rin^  to  the  base  of  the  bladder, 
where  it  opens  into  the  beginning  of  the  urethra  in  its  prostatic  part. 
Just  before  it  joins  the  urethra  each  vas  deferens  presents  a  diverticu- 
lum., the  seminal  vesicle,  which  lies  along,  and  is  attached  to,  the  base 
of  the  bladder.  The  prostate  itself,  which  surround.s  the  first  part  of 
the  urethra,  is  composed  of  a  matrix  of  unstriated  muscular  fibres, 
enclosing  numerous  branched  racemo-tubular  glands.  From  the 
point  of  entry  of  the  vasa  deferentia  to  its  orifice,  the  urethra  repre- 
sents a  common  passage  for  the  urine  and  for  the  sexual  products — the 
semen.  It  passes  therefore  through  tissues,  forming  the  penis,  which 
are  especially  adapted  for  the  purpose  of  intromission,  i.e.  the  intro- 
duction of  the  semen  containing  the  spermatozoa  into  the  female. 
In  the  urethra  we  distinguish  the  prostatic,  the  membranous,  and 
the  penile  portions.  Into  the  beginning  of  the  penile  portion,  the  bulb 
of  the  urethra,  open  the  ducts  of  the  two  glands  of  Cowper.  In  the 
penis  itself  the  urethra  is  surrounded  with  erectile  tissue,  forming  the 
corpus  spongiosum,  and  lies  between  the  two  corpora  cavernosa,  which 
consist  of  the  same  kind  of  tissue.  The  erectile  tissue  is  a  spongy  mesh- 
work  of  elastic  and  unstriated  muscle  fibres,  enclosing  spaces  in  free 
communication  with  the  efferent  veins  of  the  organ.  The  arterioles 
also  open  into  these  spaces,  but  under  normal  circimistances  both 
the  arterioles  and  the  muscle-tissues  of  the  framework  are  contracted, 
so  that  the  blood  trickles  only  slowly  from  the  arterioles  into  the 
spaces,  whence  it  escapes  readily  by  means  of  the  veins.  If  the 
muscle  fibres  be  relaxed,  so  that  blood  can  escape  readily  into  and 
distend  the  spaces,  the  tissue  swells  and  becomes  harder,  causing 
'  erection  '  of  the  organ. 

In  the  immature  testis,  i.e.  from  birth  up  to  puberty,  the  seminal 
tubules  are  filled  with  cells  \a.\.h.  large  nuclei.  Some  of  these  are  the 
spermatogonia,  the  mother  cells  of  the  future  spermatozoa,  while  the 
others  form  the  cells  of  SertoU,  whose  function  it  is  to  act  as  nurse  cells 
to  the  developing  spermatozoa.  The  actual  formation  of  spermatozoa 
begins  at  puberty,  when  the  spermatogonia  divide  many  times  to 
form  the  spermatocj-tes,  which  in  their  turn  undergo  heterqtype 
mitosis  to  form  the  spermatids,  as  already  described.  By  a  modifica- 
tion of  the  latter  the  fully  formed  spermatozoa  are  formed.  These, 
whcL  mature,  pass  by  the  tubules  of  the  testis  and  of  the  epididymis 
into  the  vas  deferens,  whence  they  make  their  way  into  the  seminal 
vesicles.  Their  movement  is  probably  facilitated  by  the  cells  lining 
the  tubule  of  the  epididymis  as  well  as  by  the  secretion  of  the  lining 
membrane  of  the  seminal  vesicles.  It  has  been  noted  that  the  sper- 
matozoa are  practically  m.otionless  while  in  the  seminiferous  tubules 
of  the  testis,  but  become  actively  motile  in  the  vas  deferens,  or  when 


1366  PHY,<^IOLOaY 

mixed  with  prostatic  secretion.  It  is  difficult  to  understand  how  the 
spermatozoa  are  conveyed  through  the  resistance  which  must  be 
offered  by  the  huge  length  of  the  tubule  of  the  epididymis,  unless  their 
onward  motion  is  facilitated  by  the  cilia-like  structures  attached  to 
some  of  the  cells  lining  this  tubule.  The  formation  of  the  spermatozoa 
is  continuous,  though  the  rate  at  which  this  occurs  is  variable  and 
regulated  by  the  sexual  activity  of  the  individual.  In  the  fully  formed 
semen  the  spermatozoa  formed  by  the  testis  are  mixed  not  only  with 
the  fluid  secreted  by  the  lining  membrane  of  the  epididymis  and  of  the 
seminal  vesicle  but  also  with  the  mucous  secretions  of  the  prostatic 
glands  and  of  Cowper's  glands.  Nevertheless  it  contains  spermatozoa 
in  enormous  numbers,  the  semen  emitted  at  a  single  act  of  coitus 
containing  as  many  as  226,000,000  spermatozoa.  Though  the  vast 
majority  of  these  are  probably  capable  of  fertilising  an  ovum,  this  act  is 
carried  out  by  only  one — a  fact  characteristic  of  the  prodigality  of 
nature  when  dealing  with  the  perpetuation  of  the  type. 

THE   FEMALE   REPRODUCTIVE  ORGANS 

The  essential  organ  of  reproduction  in  the  female  is  the  ovary,  the 
seat  of  production  of  the  ova.  The  accessory  organs  include  the  ovi- 
ducts or  Fallopian  tubes,  the  uterus,  in  which  the  fertilised  ovum  is 
retained  during  the  first  nine  months  of  its  development,  and  the 
vagina,  which  is  especially  adapted  for  the  reception  of  the  male  organ 
in  the  act  of  impregnation. 

Among  the  accessory  organs  we  may  also  reckon  the  mammary 
glands,  which  undergo  a  special  development  during  pregnancy,  and 
serve  for  the  nourishment  of  the  young  individual  during  the  first 
period  of  extra-uterine  life. 

OVULATION.  At  birth  the  ovary  consists  of  a  stroma  of  spindle- 
shaped  cells,  and  is  covered  by  a  layer  of  cubical  epithelium  (the  germ- 
epithelium)  continuous  with  the  endothelium  lining  the  general  peri- 
toneal cavity.  Embedded  in  the  stroma,  but  especially  numerous  just 
underneath  the  epithelium,  are  a  vast  number  of  '  primordial  follicles.' 
These  are  formed  during  foetal  life  by  down-gTowths  of  the  germinal 
epithelium.  Of  the  cells  prolonged  in  this  way  from  the  germinal  epithe- 
lium, some  undergo  enlargement  to  form  the  primordial  ova,  while  the 
others  are  arranged  as  a  single  layer  of  flattened  nucleated  cells,  the 
'  follicular  epithelium,'  as  a  sort  of  capsule  to  the  ovum.  Of  the  pri- 
mordial follicles,  about  70,000  are  to  be  found  in  the  ovary  of  the 
new-born  child.  During  the  first  twelve  to  fourteen  years  of  life 
they  remain  in  a  quiescent  condition.  With  the  onset  of  puberty 
one  or  more  of  the  primordial  follicles  begin  to  develop.  Indeed, 
this  development  may  be  regarded  as  the  causative  factor  in  the 
various  phenomena  which  are  characteristic  of  puberty  in  the  female 


REPRODUCTION  IN  MAN  1307 

(v.  p.  1301 ).  The  first  stage  in  the  growth  of  the  follicle  is  a  proliferation 
of  the  follicular  epithelium,  the  cells  of  which  become  cubical  and  are 
arranged  in  several  layers  round  the  ovum.  At  cue  point  in  the  mass 
of  cells  surrounding  the  ovum  a  cavity  appears  filled  with  fluid, 
the    liquor  foUiculi.      The  epithelium  thus  becom.es  separated    into 


Fig.  559.     Graafian  follicle  of  mammaliau  ovary.     (Prexant  and  BouiN.) 

01',    ovum  ;     dp,    dLscus    prolij^erus  ;     Iq.f,    liquor   foUiculi ;     ck,  thcca  ; 
gr,  membrana  granulo.«a. 

two  parts,  i.e.  the  membrana  yranulosa,  several  layers  thick,  lining 
the  whole  follicle,  and  the  discus  proligerus,  a  mass  of  cells  attached  to 
one  side  of  the  follicle,  in  which  is  embedded  the  ovum  (Fig.  559). 
Round  the  growing  follicle  the  stroma  assumes  a  concentric  arrange- 
ment and  forms  a  capsule,  of  which  the  internal  layer  consists  chiefly  of 
spindle-shaped  cells  richly  supplied  with  blood-vessels,  while  the  outer 
layer — the  (heca  externa — is  made  up  of  a  tough  fibrous  tissue.  With  the 
growth  of  the  follicle  the  ovnni.  also  becomes  larger  and  surrounds  itself 
with  a  distinct  m.embranc.  known  as  the  zona  pellucida.    This  membrane 


1368  PHYSIOLOGY 

presents  a  fine  radial  striation,  which  is  supposed  to  indicate  the 
existence  of  canals  through  which  the  ovum  can  obtain  sustenance 
from  the  surrounding  cells  of  the  follicular  epithelium.  The  nucleus 
also  becomes  larger,  and  forms  the  germinal  vesicle  containing  one  or 
two  well-marked  nucleoli — the  germinal  spot.  The  mature  Graafian 
follicle  projects  from  the  surface  of  the  ovary  as  a  transparent  vesicle 
about  the  size  of  a  pea.  (Its  diameter  is  about  15  mm.)  In  the 
process  of  growth  the  ovum  has  increased  from  a  diameter  of  25^  to 
200  fx.  Before  the  ovum  can  undergo  fertilisation  the  double  division 
of  the  nucleus,  or  germinal  vesicle,  has  to  take  place,  which  leads  to 
the  formation  and  extrusion  of  the  two  polar  bodies.  This  process 
probably  occurs  just  before  or  just  after  the  discharge  of  the  ovum 
from  the  ovary. 

With  increasing  size  of  the  Graafian  follicle  the  membrane  covering 
it  becomes  progressively  thinner.  At  certain  periods,  or  under  certain 
conditions,  the  membrane  ruptures,  and  the  ovum  is  discharged  in 
the  liquor  foUiculi,  still  surrounded  by  an  adherent  mass  of  the  cells 
of  the  discus  proliferus.  In  some  animals  this  process  of  ovulation 
occurs  at  definite  periods  of  the  year.  In  others,  such  as  the  rabbit, 
the  occurrence  of  ovulation  depends  upon  coitus  taking  place  during 
the  period  of  sexual  activity.  We  shall  have  later  to  discuss  the 
relation  of  ovulation  in  the  human  female  to  the  periodic  changes 
occurring  in  the  other  parts  of  the  reproductive  apparatus. 

After  the  discharge  of  the  ovum  the  remaining  portions  of  the 
follicle  undergo  a  characteristic  series  of  changes,  which  result  in  the 
production  of  the  corjms  luteum.  Immediately  after  the  rupture 
the  follicle  becomes  filled  with  blood,  apparently  resulting  from  the 
sudden  release  of  the  pressure  on  the  capillaries  in  the  walls  of  the 
foUicle.  The  cells  of  the  membrana  granulosa  rapidly  increase  in  size,  a 
few  of  them  undergoing  mitotic  division,  so  that  a  dense  mass  of  cells  is 
formed,  nearly  filling  the  original  follicle.  At  the  same  time  the  cells  of 
the  internal  theca  proliferate,  with  the  formation  of  connective  tissue, 
which  grows  in  among  the  cells  filling  the  Graafian  follicle.  These  cells 
finally  attain  a  size  four  or  five  times  that  of  the  cells  of  the  membrana 
granulosa  in  the  mature  follicle.  Blood-vessels  grow  from  the  external 
theca  towards  the  centre  of  the  follicle.  The  cells  within  the  follicle 
then  undergo  fatty  degeneration  and  present  a  yellow  colour  due 
to  a  fatty  pigment  known  as  lutein.  The  corpus  luteum,  as  the  body 
so  formed  is  called,  attains  its  greatest  size  about  a  week  after  ovula- 
tion, and  then  gradually  undergoes  regressive  changes.  If,  however, 
the  ovum,  which  has  been  discharged,  undergoes  fertilisation,  and 
pregnancy  results,  the  corpus  luteum  continues  to  grow  for  a  con- 
siderable time  and  attains  its  largest  size  at  about  the  third  month 
of  pregnancy.     It  does  not  entirely  disappear  until  after  the  end  of 


REPRODUCTION"  IN  MAN 


1309 


pregnancy.  The  big  corpus  luteum  found  in  pregnancy  is  often 
spoken  of  as  the  '  true  '  corpus  luteum,  and  is  distinguished  from  the 
corpus  luteum  spuriuni  of  menstruation  or  of  ovulation  without 
fertilisation.  There  is,  however,  no  essential  difference  other  than  that 
of  size  between  these  two  kinds  of  corpus  luteum.  It  must  not  be 
imagined  that  all  tlie  70,000  primordial  follicles  found  in  the  ovary  of 
a  new-born  child  undergo  this  series  of  changes  ;  it  is  probable  that  in 
the  human  female  ovulation  occurs,  as  a  rule,  once  every  four  weeks 
during  the  tliirty-five  years  of    sexual  life.     A  vast  number  of  the 


Fig.  560.     Fully  developed  eoipus  luteum  of  the  mouse.     (Sobotta.) 

Graafian  follicles,  after  developing  to  a  certain  extent,  undergo 
regressive  changes,  both  during  childhood  and  during  adult  life.  The 
cellular  elements  degenerate,  leucocytes  wander  into  the  follicle  and 
attack  the  degenerating  ovum,  so  that  finally  the  follicle  is  replaced 
by  connective  tissue,  without  the  formation  of  any  corpus  luteum. 

MENSTRUATION.  Puberty  in  the  girl  is  marked  by  the  onset  of 
menstruation.  Under  this  term  is  understood  a  flow  of  blood  and 
mucus  from  the  uterus,  which  recurs  every  four  weeks  and  lasts  each 
time  from  four  to  five  days.  Before  the  first  menstrual  period,  other 
signs  of  puberty,  i.e.  of  approaching  sexual  maturity,  are  usually 
observed.  These  include  rapid  growth,  with  changes  in  the  skeleton, 
leading  to  the  typically  feminine  type  of  pelvis,  a  development  of 
the  mamnuiry  glands,  and  tlic  growth  of  hair  on  the  pube^.  At  the 
same  time  there  is  increased  development  of  the  mental  characteristics 


1370  PHYSIOLOGY 

which  are  typical  of  the  sex.  The  amount  of  blood  lost  at  each  men- 
strual period  varies  between  100  and  300  orm.  Durin*i  the  '  period  ' 
there  are  often  disturbances  of  other  functions  of  the  body,  which  are 
so  common  that  to  be  '  unwell '  is  the  recognised  polite  description 
of  the  menstrual  period.  Thus  it  is  often  attended  with  pains  in  the 
abdomen,  a  feeling  of  weight  and  fulness,  disturbance  of  digestion, 
headache,  and  neuralgias  of  various  distribution.  At  the  same  time 
there  is  a  general  disinclination  for  exertion. 

Menstruation  is  due  to  periodic  changes  in  the  uterine  m.ucous 
membrane.  During  the  few  days  previous  to  the  period  the  mucous 
membrane  undergoes  a  rapid  hypertrophy,  increasing  in  thickness 
from  2  mm.  to  6  mm.  At  the  same  time  there  is  increased  vascularity 
of  the  membrane  in  consequence  of  dilatation  of  its  blood-vessels.  At 
the  commencement  of  the  menstrual  period  there  is  an  escape  of  the 
red  blood-corpuscles,  chiefly  by  diapedesis,  but  partly  by  actual 
rupture  of  the  blood-capillaries  into  the  spaces  between  the  uterine 
glands.  At  this  period  sections  of  the  uterine  mucous  membrane 
show  numerous  collections  of  red  blood-corpuscles,  lying  immediately 
under  the  superficial  epithelium.  In  some  cases  this  stage  is  followed 
by  an  almost  complete  descjuamation  of  the  superficial  epithelium.. 
Generally  the  desquamation  is  only  partial,  but  in  either  case  the 
blood  escapes  into  the  cavity  of  the  uterus,  where  it  becomes  mixed 
with  the  increased  secretion  from,  the  uterine  glands  and  is  discharged 
into  and  from  the  vagina  as  the  menstrual  fluid.  With  the  occur- 
rence of  the  menstrual  flow  the  mucous  membrane  begins  to  dim.inish 
in  thickness.  The  vascularity  decreases,  and  nmch  of  the  blood  in 
the  deeper  parts  of  the  mucosa  becomes  reabsorbed.  The  desquamated 
epithelium  is  replaced  by  proliferation  of  the  cells  which  remain  intact, 
so  that  finally  the  mucosa  is  completely  regenerated  and  brought  back 
to  its  original  condition.  This  period  of  regeneration  lasts  about 
fourteen  days.  During  the  next  few  days  the  condition  of  the  mem- 
brane is  stationary,  but  this  period  of  rest  lasts  but  a  short  tim.e,  since 
signs  of  the  pre -menstrual  swelling  can  be  detected  as  early  as  three 
days  before  the  onset  of  the  next  menstrual  period. 

THE  RELATION  OF  OVULATION  TO  MENSTRUATION 
There  is  no  doubt  that  m.enstruation  depends  on  the  functional 
activity  of  the  ovary.  Its  onset  coincides  with  the  first  production  of 
ripe  ova  in  the  ovary,  and  it  ceases  with  the  cessation  of  ovulation 
at  the  climacteric  or  m_enopause.  In  cases  where  the  ovaries  have 
been  removed  before  puberty  menstruation  never  occurs.  Removal 
of  both  ovaries  during  adult  life  generally  brings  about  a  premature 
menopause.  It  seems  probable  that  the  ripening  of  the  ova  in  the 
human  ovary  occurs  at  periods  corresponding  to  those  of  menstrua- 


REPRODUCTION  IN  MAN  1371 

tion.  But  there  has  been  much  division  of  opinion  as  to  the  exact 
relation  between  the  two  processes.  Fairly  definite  clinical  and  post- 
mortem evidence  has  beeji  brought  forward  for  the  theory  that  ovula- 
tion precedes  the  nienstrual  flow.  On  this  theory  the  de<,'eneration  of 
the  uterine  mucous  membrane,  which  occurs  at  each  period,  repre- 
sents, so  to  speak,  the  undoing  of  a  preparation  for  the  reception  of 
a  fertihsed  ovum.  The  ovum  has  been  discharged,  the  mucous  mem- 
brane has  been  prepared  for  its  reception,  but  fertilisation  not  having 
taken  place,  ovum  and  mucous  membrane  are  cast  out  together  in 
the  menstrual  flow.  Unfortunately  almost  equally  definite  clinical 
evidence  has  been  adduced  for  the  view  that  ovulation  occurs  during 
or  after  the  menstrual  period.  Light  is  thrown  upon  the  question 
by  the  study  of  the  phenomena  of '  rut '  or  '  heat '  in  the  lower  animals. 
In  most  mammals  impregnation  and  conception  can  only  occur  at 
certain  definite  periods  of  the  year.  At  these  seasons  the  female 
presents  a  swelling  of  the  mucous  membrane  of  the  external  genitals, 
and  often  a  flow  of  blood  or  mucus.  As  a  rule  it  is  only  when  in  this 
condition  that  it  will  permit  the  approach  of  the  male.  Thus  the  bitch 
'  comes  on  heat '  as  a  rule  twice  in  the  year  ;  the  cat  three  or  four 
times  ;  most  carnivora  only  once  a  year.  At  these  periods  the  uterus 
shows  well-marked  histological  changes,  which  may  be  divided  into 
the  following  periods  : 

(1)  The  period  of  rest.  During  this  time,  which  extends  over  the 
greater  part  of  the  year,  the  mucous  membrane  is  thin  and  pale.  The 
period  of  heat  being  known  as  the  oestrus,  this  first  period  is  denoted 
by  Heape  the  ana  strum. 

(2)  The  period  of  growth  or  congestion.  This  corresponds  to  the 
pre-menstrual  thickening  of  the  mucous  membrane  of  the  human 
female. 

(3)  Period  of  destruction,  associated  with  haemorrhages  into  the 
mucous  membrane,  desquamation  of  the  superficial  epithelial  cells, 
and  occasionally  discharge  of  blood  and  mucus  from  the  vagina. 
These  two  periods  are  grouped  together  as  the  pro-oestnim. 

(4)  Period  of  recuperation  corresponding  to  the  post -menstrual 
regeneration  of  the  mucous  membrane.  It  is  during  the  first  part 
of  this  period  or  at  the  very  end  of  the  last  period  that  ovulation  occurs 
in  those  animals  where  ovulation  is  independent  of  coitus.  It  is  at 
this  time,  too,  that  the  animal  exhibits  sexual  desire  and  permits  the 
approaches  of  the  male.  If  fertilisation  occurs,  the  mucous  membrane 
undergoes  rapid  hypertrophy,  much  more  marked  than  that  occurring 
during  the  pro-a3Strum.  In  the  absence  of  impregnation  the  mucous 
membrane  returns  to  the  condition  of  rest,  the  stage  of  return  being 
known  as  the  nxetwstrum. 

These  results  have  been  found  by  Heape  and  Marshall  to  apply  to 


1372  PHYSIOLOGY 

a  large  number  of  different  mammals.  We  are  therefore  justified  in 
concluding  that  menstruation  is  the  physiological  homologue  of  the 
pro-oestrum  in  the  lower  mammals,  and  that  ovulation  occurs,  or  at 
any  rate  that  the  ova  attains  maturity,  after  or  at  the  very  end  of 
the  menstrual  flow.  If  we  consider  that  the  ovum  may  take  some 
days  to  pass  down  the  Fallopian  tube  to  the  uterus,  and  that  the 
spermatozoa  may  retain  their  vitality  for  ten  days  or  more  in  the 
Fallopian  tubes  or  uterus,  it  is  evident  that  in  man  impregnation  may 
take  place  at  any  time  between  two  nienstrual  periods.  Desire  is 
thus  not  limited  to  certain  seasons,  as  is  the  case  with  most  of  the 
lower  animals. 

FERTILISATION 

The  act  of  impregnation  consists  in  the  introduction  of  sperma- 
tozoa into  the  female  genital  tract,  where  they  may  come  in  contact 
with  and  fertilise  the  ovum,  which  is  discharged  from  the  ovary  by 
bursting  of  a  Graafian  follicle.  This  is  effected  in  the  act  of  coitus  or 
sexual  congress  by  the  insertion  of  the  penis  into  the  vagina  of  the 
female.  Before  this  can  occur  erection  of  the  male  organ  must  take 
place.  The  mechanism  of  erection  is  twofold.  The  most  important 
factor,  as  was  shown  by  Eckhard  and  Loven,  is  an  active  dilatation  of 
the  vessels  of  the  penis,  especially  of  the  medium-sized  and  smaller 
arteries.  If  the  penis  be  cut  across  while  in  the  flaccid  condition, 
venous  blood  merely  trickles  away  from  the  cut  surface,  whereas,  if 
erection  be  excited,  the  flow  of  blood  from  the  cut  surface  is  increased 
eight  to  ten  times,  and  the  blood  becomes  bright  arterial  in  colour.  It 
is  thus  possible  to  excite  erection  in  an  animal,  in  whom  the  second 
factor  has  been  abolished  by  paralysing  the  muscles  by  means  of 
curare.  This  second  factor  is  the  contraction  of  the  ischio-cavernosus  or 
erector  'penis  muscle,  certain  fibres  of  which  pass  over  the  dorsal  vein 
of  the  penis  and  compress  this  vessel  when  they  contract.  Since 
ligature  of  the  veins  coming  from  the  penis  does  not  produce  erection, 
the  contraction  of  this  muscle  must  be  regarded  as  simply  aiding 
the  efiects  of  the  arterial  dilatation. 

Before  or  at  the  beginning  of  coitus  analogous  changes  occur  in 
the  female  organs,  leading  to  erection  of  the  clitoris  and  of  the  erectile 
structures  of  the  vulva.  The  glands  of  the  vulva,  especially  the  glands 
of  Bartholini,  secrete  a  mucous  fluid,  thus  lubricating  the  passage 
into  the  vagina.  The  friction  between  the  glans  penis  and  the  wall  of 
the  vagina  causes  a  reflex  discharge  of  motor  impulses  in  both  male 
and  female.  In  the  former  the  muscular  walls  of  the  vasa  deferentia 
and  seminal  vesicles  enter  into  rhythmic  contractions,  thus  forcing 
the  spermatozoa  they  contain  into  the  urethra.  The  spermatozoa, 
mixed  with  the  secretions  of  the  epididymis,  the  seminal  vesicles, 


REPRODUCTION  IN  MAN  1373 

the  prostatic  glands,  and  the  glands  of  Cowper,  form  the  semen, 
which  is  pressed  along  the  urethra  by  rhythmical  contractions, 
from  behind  forwards,  of  the  bulbo-  and  ischio-cavernosi  muscles. 
It  has  been  stated  that  movements  take  place  coincidently  in  the 
uterus,  so  that  its  axis  more  nearly  corresponds  to  that  of  the  vagina. 
The  movement  of  the  semen  along  the  uterus  and  Fallopian  tubes 
is  ascribed  by  certain  observers  to  an  antiperistaltic  contraction 
of  these  organs.  A  more  important  factor  is  probably  the  move- 
ment of  the  spermatozoa  themselves.  As  we  have  already  seen, 
these  are  introduced  into  the  female  passage  in  countless  numbers. 
They  will  be  chemiotactically  attracted  by  the  alkaline  mucus,  secreted 
by  and  filling  the  cervix  of  the  uterus.  When  they  have  entered  this 
organ  they  will  meet  the  downward  stream  of  mucus  impelled  by 
the  action  of  the  cilia  lining  the  uterus  and  Fallopian  tubes.  It  seems 
probable  that  their  reaction  to  this  current  is  to  swim  *  against  it 
(positive  rheotaxis),  so  that  they  reach  the  upper  part  of  the  Fallopian 
tubes  or  the  surface  of  the  ovary  itself.  Fertilisation  of  the  ovum 
occurs  in  most  cases  in  the  Fallopian  tube,  and  the  fertilised  ovum  is 
then  carried  slowly  down  the  tube  into  the  uterus. 

NERVOUS  MECHANISM  OF  IMPREGNATION.  Although,  in 
both  sexes,  coitus  is  attended  by  a  high  degree  of  psychical  excite- 
ment, yet  it  is  essentially  a  spinal  reflex,  and  can  be  carried  out 
when  all  impulses  from  the  higher  centres  are  cut  off  by  section 
of  the  cord  in  the  dorsal  region.  The  centre  presiding  over  the 
act  is  situated  in  the  lumbar  spinal  cord.  The  external  generative 
organs,  like  the  bladder,  are  supplied  from  two  sets  of  nerve  fibres 
— from  the  lumbar  nerves  through  the  sympathetic,  and  from  the  sacral 
nerves.  The  fibres  from  the  lumbar  nerves  arise  in  the  cat  from  the 
second,  third,  and  fourth,  or  the  third,  fourth,  and  fifth  lumbar  nerve- 
roots,  and  in  the  dog  from  the  thirteenth  thoracic,  and  the  first  to 
the  fourth  lumbar  roots.  They  run  in  the  white  rami  communicantes 
to  the  sympathetic  chain,  whence  they  may  take  two  paths. 

(a)  The  great  majority  of  the  fibres  run  down  the  sympathetic 
chain  to  the  sacral  ganglia,  whence  fibres  are  given  off  in  the  grey  rami 
communicantes  to  the  sacral  nerves  ;  their  further  course  is  by  the 
pudic  nerves,  none  running  in  the  nervi  erigentes. 

(6)  A  few  fibres  go  by  the  hypogastric  nerves  to  the  pelvic 
plexus. 

Excitation  of  these  fibres  causes  contraction  of  the  arteries  of 

*  Spermatozoa  movi"  in  a  straight  line,  at  tlio  rato  of  2-3  mm.  per  minute. 
Thus  tliey  might  traverse  the  distance  of  16-20  cm.  bi'twc^en  the  os  uteri 
and  the  trumpi-t -shaped  orifice  of  tlie  Fallopian  tubes  in  three-quarters  of  an 
hour.  In  animals  sptTmatozoa  have  been  found  at  the  peritoneal  end  of  the 
Fallopian  tubes  withrn  an  hour  or  two  after  coitus. 


1374  PHYSIOLOGY 

the  penis,  and  of  the  unstriated  muscles  of  the  tunica  dartos  of  the 
scrotum.  In  animals  which  possess  a  retractor  penis  muscle,  excita- 
tion of  the  lumbar  nerves  causes  strong  contraction  of  the  muscle. 

The  fibres  from  the  sacral  nerves  can  be  divided  into  two  classes — - 
visceral  and  somatic.  The  visceral  branches  run  in  the  pelvic  nerves, 
or  nervi  erigentes.  Stimulation  of  these  fibres  produces  active  dilata- 
tion of  the  arteries  of  the  penis  or  vulva,  and  also  inhibition  of  the 
unstriated  muscle  of  the  penis,  the  retractor  muscle  of  the  penis, 
when  present,  and  of  the  vulva  muscles.  The  somatic  branches 
supply  motor  nerves  to  the  ischio-  and  bulbo-cavernosi,  as  well  as  the 
constrictor  urethrse.  In  the  female  they  supply  the  analogous  muscles, 
namely,  the  erector  clitoridis  (ischio-cavernosus)  and  the  sphincter 
vaginae  (bulbo-cavernosus).  Both  these  sets  of  fibres  are  therefore 
involved  in  the  erection  of  the  generative  organs  which  accompanies 
coitus. 

The  internal  organs,  i.e.  the  uterus  and  vagina  in  the  female,  and 
vasa  deferentia,  seminal  vesicles,  and  uterus  masculinus  in  the  male, 
differ  from  the  external  organs  in  receiving  no  efferent  nerve  fibres 
from  the  sacral  nerves,  as  has  been  pointed  out  by  Langley  and 
Anderson.  They  are  supplied  with  fibres,  which  pass  out  through  the 
anterior  roots  of  the  third,  fourth,  and  fifth  lumbar  nerves  (in  the 
rabbit  and  cat),  and  run  through  the  sympathetic  to  the  inferior 
mesenteric  ganglia,  whence  they  proceed  by  the  hypogastric  nerves. 
On  stimulating  these  fibres,  two  effects  are  produced  on  the  uterus  and 
vagina,  namely,  a  contraction  of  the  small  arteries,  leading  to  pallor 
of  the  organs,  and  a  strong  contraction  of  the  muscular  coats.*  In  the 
vagina  the  contraction  can  usually  be  seen  to  start  from  one  end  and 
spread  to  the  other.  The  whole  then  remains  for  a  time  in  a  state  of 
powerful  tonic  contraction,  which  affects  both  longitudinal  as  well  as 
circular  muscles.  In  the  male  stimulation  of  these  nerves  excites 
contraction  of  the  whole  musculature  of  the  vasa  deferentia  and 
seminal  vesicles,  which  may  be  strong  enough  to  cause  emission  of 
semen  from  the  penis.  These  effects  on  the  uterus  and  seminal  vesicles 
are  not  abolished  by  injection  of  atropine. 

The  course  of  the  sensory  fibres  from  the  generative  organs  to  the 
lumbo-sacral  cord  has  not  yet  been  fully  made  out,  but  it  seems 
probable  that  it  corresponds  to  the  course  taken  by  the  efferent  fibres. 

An  accessory  genital  muscle,  the  retractor  penis,  which  is  found  in  the 
dog,  cat,  horse,  donkey,  hedgehog  (not  in  the  rabbit  or  man),  presents  con- 
siderable physiological  interest.  It  was  first  described  by  Eckhard  as  the 
Afterruthenhand,  and  consists  of  a  thin  band  of  longitudinally  arranged 
unstriated  muscle  (15  to   20  cm.  long   in   a   spaniel  weighing   about  15  kilos), 

*  Under  some  circumstances  stimulation  of  the  sympathetic  nerves  may 
cause  relaxation  of  the  uterus. 


REPRODUCTION  IN  MAN  1375 

which  is  inserted  at  the  attachment  of  the  prepuce,  and  is  continued  backwards 
in  a  sheath  of  connective  tissue  to  the  bulb,  wiien  it  divides  into  two  sb'ps  which 
pass  on  either  side  of  the  anus.  A  few  striated  fibres  are  found  in  tlie  Vjack  part  of 
this  muscle,  derived  from  tiie  external  sphincter  of  the  anus  and  the  bulbo-caver- 
nosus  muscles.  This  muscle  is  extremely  sensitive  to  changes  of  temperature,  and 
is  at  the  same  time  very  tenacious  of  hfe.  Thus  it  may  be  cut  out  of  the  body  and 
kept  in  serum  or  blood,  in  a  cool  place,  for  two  days.  At  the  end  of  this  time 
it  will,  on  warming,  relax,  and  enter  into  spontaneous  rhji;hmic  contractions. 
At  about  40^  C.  the  muscle  is  quite  flaccid.  On  cooling  slightly  (to  3.5°)  it 
will  shorten,  and  at  the  same  time  may  enter  into  slow  rhj'thmic  contractions. 
If  cooled  to  1.5°  C.  the  muscle  will  contract  to  about  a  quarter  of  its  previous 
length.  The  same  shortening  may  be  produced  on  exciting  the  muscle  with 
strong  interrupted  currents. 

The  muscle  is  innervated  from  two  sources,  the  two  nerves  having 
antagonistic  actions  {cp.  p.  276).  The  motor  fibres  to  the  muscle  are  derived 
from  the  lumbar  sympathetic  {i.e.  the  upper  set  of  nerve-roots),  and  run  to  the 
muscle  in  the  internal  pudic  nerve.  The  pehnc  nerves,  on  the  other  hand, 
carry  inhibitory  impulses  to  the  muscle,-  thus  enabling  the  concomitant 
vascular  dilatation  to  take  effect  in  producing  erection  of  the  penis. 


SECTION  IV 
PREGNANCY  AND  PARTURITION 

PREGNANCY 

Fertilisation  of  the  ovum  takes  place,  as  a  rule,  in  the  Fallopian 
tube.  Directly  one  spermatozoon  has  penetrated  into  the  ovum,  a 
membrane  is  formed  round  the  yolk,  which  prevents  the  entrance  of 
any  other  spermatozoa.  The  fusion  of  the  male  and  female  pro- 
nuclei is  followed  immediately  by  division  of  the  fertilised  ovum,  so 
that,  by  the  time  it  arrives  in  the  uterus  (about  eight  days  after 
fertilisation),  it  consists  of  a  mass  of  cells  known  as  the  morula.  At 
this  time  the  ovum  has  a  diameter  of  about  0-2  mm.  Pregnancy  in  the 
human  being  lasts  about  nine  months,  birth  generally  taking  place 
280  days,  i.e.  ten  periods  after  the  last  menstrual  period.  During 
pregnancy  menstruation  is  absent. 

With  the  arrival  of  the  fertilised  ovum  in  the  uterus,  extensive 
changes  begin  in  this  and  the  neighbouring  organs  of  generation.  The 
virgin  uterus  is  pear-shaped,  and  its  cavity  amounts  to  about  2-5  c.c. 
Just  before  birth  the  volume  of  the  uterus  is  about  5000-7000  c.c, 
and  the  walls  of  the  organ  are  thickened  in  proportion.  In  the  hyper- 
trophy of  the  uterine  wall  all  its  elements  are  involved,  but  especially 
the  muscle-cells.  It  is  doubtful  whether  there  is  an  actual  new  forma- 
tion of  muscle  fibres,  but  each  fibre  grows  in  length  and  thickness, 
becoming  finally  between  seven  and  eleven  times  as  long  and  three  to 
five  times  as  thick  as  in  the  unimpregnated  uterus  (Fig.  561).  There 
is  at  the  same  time  a  great  growth  of  the  blood-vessels,  which  have 
to  supply  not  only  the  growing  wall  of  the  uterus  but  also,  by  means 
of  a  special  organ^ — the  placenta, — the  nutritional  needs  of  the 
developing  foetus. 

CHANGES  IN  THE  UTERINE  MUCOUS  MEMBRANE.  At  the 
moment  of  conception  the  uterine  mucous  membrane  begins  to  undergo 
hypertrophy.  Within  fourteen  days  it  has  attained  a  thickness  of 
\  cm.,  and  by  the  end  of  the  second  month,  |  cm.  On  section  it  shows 
a  compact  layer,  lining  the  cavity  of  the  uterus,  and  beneath  this, 
abutting  on  the  muscular  tissue,  is  a  spongy  layer  three  times  as  thick 
as  the  compact  layer.  The  superficial  epithelium  becomes  flattened, 
loses  its  cilia,  and  degenerates.     In  the  spongy  layer  the  uterine  glands 

1376 


PREGNANCY  AND  PARTl^ITION 


]:i7 


proliferate,  the  stroma  cells  are  enlari^ed,  and  the  blood-capillaries 
are  widely  dilated.  The  stroma  cells  become  converted  into  the 
large  decidual  cella.  By  the  time  the  fertilised  ovum  arrives  in  tlw 
uterus  the  process  of  hypertrophy  and  loosening  of 
the  layers  of  the  mucous  membrane  has  already 
made  some  progress.  As  it  lies  on  the  mucous 
membrane,  the  outermost  cells  of  the  developing 
ovum  exercise  a  destructive  influence  on  the  ad- 
jacent cells  of  the  mucous  membrane,  apparently 
through  some  sort  of  digestion,  so  that  the  ovum 
sinks  in  the  membrane  and  reaches  the  subepithelial 
connective  tissue.  Round  the  margins  of  the  de- 
pression, which  the  ovum  has  made  for  itself,  the 
mucous  membrane  grows  over  the  protruding  part  of 
the  ovum  (Fig.  562).  When  this  has  taken  place, 
the  different  parts  of  the  mucous  membrane  receive 
different  names.  Since  (in  man)  they  are  all  to  be 
cast  off  with  the  foetus  at  birth,  each  part  is  spoken 
of  as  the  decidua,  that  lining  the  main  body  of  the 
uterus  being  known  as  the  decidua  vera,  that  cover- 
ing the  protruding  part  of  the  egg  as  the  decidua 
reflexa,  while  that  to  which  the  egg  is  immediately 
attached  is  the  decidua  serotina  or  basalis.  It  is  from 
the  latter  that  the  placenta  is  formed.  By  the  end 
of  the  second  week  the  blood-vessels  in  this  situa- 
tion are  considerably  enlarged.  This  enlargement 
proceeds,  affecting  especially  the  capillaries  and 
veins,  until  these  form  venous  sinuses  at  the  junc- 
tion between  the  mucous  membrane  and  the 
muscular  coat.  Changes  take  place  at  the  same 
time  in  the  embryo.  When  it  sinks  into  the  mucous 
membrane  it  has  a  diameter  of  1  mm.  The  blasto- 
derm is  fully  formed  with  its  three  layers  ;  the  yolk- 
sac,  the  body  cavity,  and  the  amnion  are  present. 
The  outermost  layer  of  the  ejjiblast  becomes 
specially  modified  to  serve  for  the  nutrition  of  the 
embryo,  and  gives  rise  to  the  production  of 
numerous  viUi,  the  chorionic  villi,  so  that  the 
whole  ovum  has  a  shaggy  appearance.  Since  this  tissue  takes  no 
part  in  the  further  development  of  the  embryo,  but  serves  simply 
for  its  nutrition,  it  is  often  spoken  of  as  the  trophohlast.  With  the 
formation  of  foetal  blood-vessels,  these  penetrate  into  the  villi,  together 
with  mesoblast.  The  vilU  grow  into  the  venous  spaces,  especially  in 
the  basal  part  of  the    decidua,  so    that,    at    this   period,  the  foetal 


Fig.    561.     Isolated 

musclc-ccUs     from 

the  uteru-s,  showing 

the      hyiKTtrophy 

duriug  pregnancy. 

a,  fibre  from  utcru.s 

in    ninth    month  of 

pregnaney  ;    b,  fibre 

from    a    non-gravid 

uterus.(AftcrBuMM.) 


1378 


PHYSIOLOGY 


villi  are  immersed  in  maternal  blood,  the  foetal  blood-vessels  being 
separated  from  the  maternal  blood  by  a  double  layer  of  epitheUum, 
one  layer  of  which  is  maternal  and  the  other  foetal  in  origin.  Later 
these  cells  become  reduced  to  a  single  laver. 


Fig.  562.  Diagram  to  illu.strate  the  imbedding  of  the  ovum  in  the  decidua. 
and  the  first  formation  of  the  foetal  villi  in  the  form  of  a  sjTicytial 
iropkoblasi  (derived  from  the  outer  layer  of  the  ovum)  which  is  invading 
sinus-like  blood-spaces  in  the  decidua.     (After  T.  H.  Bkyce.) 


NUTRITION  OF  THE  EMBRYO.  At  the  earliest  period  of  its 
development  the  fertilised  ovum  is  dependent  for  its  nourishment 
on  the  remains  of  the  cells  of  the  discus  proliferus  adhering  to  it,  or 
on  the  fluid  of  the  Fallopian  tube  in  which  it  is  immersed.  The  first 
blood-vessels  which  are  formed  serve  to  take  up  nourishment  from 
the  yolk-sac.  In  man,  however,  this  source  of  supply  is  insignificant, 
and  from  the  second  week  onwards  blood-vessels  traversing  the 
chorionic  villi  come  into  close  relation  with  the  maternal  blood,  from 
which,  henceforth,  the  whole  growth  of  the  foetus  is  to  be  maintained 
by  a  special  development  of  these  connections  in  the  placenta. 

In  the  fully  formed  foetus  blood  passes  from  the  foetus  to  the 
placenta  by  the  umbihcal  artery,  and  is  returned  by  the  umbilical 
veins.  There  is  no  conamunication  between  foetal  and  maternal  cir- 
culations. The  placenta  represents  the  foetal  organ  for  respiration, 
nutrition,  and  excretion.  Thus  the  umbilical  artery  carries  to  the 
placenta  a  dark  venous  blood,  which  in  this  organ  loses  carbonic  acid 
and  takes  up  oxygen,  so  that  the  blood  of  the  umbilical  vein  is  arterial 
in  colour.     The  oxygen  requirements  of  the  foetus  are,  however,  but 


PREGNANCY  AND  PARTURITION  i:i79 

small.  It  is  protected  from  all  loss  of  heat,  movements  are  sluggish 
or  for  the  most  part  absent,  and  the  only  oxidative  processes  are 
those  required  in  the  building  up  of  the  developing  tissues.  On  the 
other  hand,  the  foetus  has  need  of  a  rich  supply  of  food-stuffs,  which  it 
must  obtain  through  the  placental  circulation.  It  is  imagined  that  the 
epithelium  covering  the  villi  serves  as  an  organ  for  passing  on  the 
necessary  food-stuffs  from  the  maternal  to  the  foetal  blood  in  the  form 
best  adapted  for  the  requirements  of  the  foetus.  We  know,  however, 
practically  nothing  as  to  the  changes  or  mechanism  involved  in  this 
transference.  Although  most  of  the  organs  of  the  foetus  are  fully 
formed  some  time  before  birth,  they  are  for  the  most  part  in  a  state  of 
suspended  activity.  The  nitrogenous  excreta  are  turned  out  by 
the  placenta,  so  that  the  foetal  secretion  of  urine  is  minimal  or  absent. 
The  alimentary  apparatus  is  for  the  most  part  ready.  Thus  pepsin  can 
be  extracted  from  the  foetal  gastric  mucous  membrane.  The  pancreas 
contains  trypsinogen  and  the  intestinal  mucous  membrane  pro- 
secretin. Amylolytic  ferments  seem,  however,  to  be  absent  both  from 
the  salivary  glands  and  the  pancreas.  The  liver  stores  up  glycogen 
and  secretes  bile,  which  accumulates  in  the  small  intestine,  forming 
the  '  meconium.'  This  is  generally  voided  by  the  child  shortly  after 
birth. 

THE  FCETAL  CIRCULATION.  In  the  foetus,  from  the  middle  of 
intra-uterine  life,  we  find  certain  arrangements  of  the  circulation  which 
are  directed  to  providing  the  fore  part  of  the  body,  especially  the  rapidly 
growing  brain,  with  oxygenated  blood,  while  the  less  important  tissues 
of  the  Umbs  and  trunk  receive  venous  blood  (Fig.  563).  The  arterial 
blood  coming  from  the  placenta  along  the  umbiUcal  veins  can  pass 
directly  into  the  liver.  The  greater  part  of  it,  however,  traverses  the 
ductus  venosus  to  enter  the  inferior  vena  cava,  by  which  it  is  carried  to 
the  right  auricle.  Here  it  impinges  on  the  Eustachian  valve,  and  is 
directed  thereby  through  the  foramen  ovale  into  the  left  auricle,  whence 
it  passes  into  the  left  ventricle  to  be  driven  into  the  aorta.  As  this 
arterial  blood  passes  into  the  inferior  cava,  it  is  of  course  mixed  with 
the  venous  blood,  returning  from  the  lower  limbs  and  lower  part  of 
the  trunk.  By  the  aorta  this  mixture,  containing  chiefly  arterial 
blood,  is  carried  to  the  head  and  fore  limbs.  The  venous  blood  from 
these  parts  is  carried  by  the  superior  vena  cava  to  the  right  auricle, 
and  thence  to  the  right  ventricle,  by  which  it  is  driven  into  the  pul- 
monary artery.  Only  a  small  part  of  the  blood,  however,  passes 
through  the  lungs,  the  greater  part  traversing  the  patent  diu^ius 
arteriosus  to  be  discharged  into  the  aorta  below  the  arch,  whence  it 
flows  partly  to  the  lower  hmbs  and  trunk,  but  chiefly  to  the  placenta 
by  the  umbilical  arteries.  In  the  fu-tus  therefore  the  work  of  the 
circulation  is  largely  carried  out  by  the  right  ventricle.     The  greater 


1380  PHYSIOLOGY 

thickness  of  the  left  ventricular  walls,  which  is  so  characteristic  of 
the  adult,  does  not  become  evident  until  shortly  before  birth. 


Fig.  563.  Diagrammatic  outline  of  the  organs  of  circulation  in  the 
foetus  of  six  months.  (After  Allen  Thojison.) 
RA,  right  auricle  of  the  heart  ;  RV,  right  ventricle  ;  la,  left  auricle  ; 
EV,  Eustachian  valve  ;  LV,  left  ventricle  ;  L,  liver  ;  K,  left  kidney  ;  i,  portion 
of  small  intestine  ;  a,  arch  of  the  aorta  ;  a',  its  dorsal  part ;  a",  lower  end  ; 
vcs,  superior  vena  cava  ;  i-ci,  inferior  vena  ■where  it  joins  the  right  auricle  ; 
vci,  its  lower  end  ;  s,  subclavian  vessels  ;  j,  right  jugular  vein  ;  c,  common 
carotid  arteries  ;  four  curved  dotted  arrow  lines  are  carried  through  the 
aortic  and  pulmonary  opening  and  the  auriculo-ventricular  orifices ;  da 
opposite  to  the  one  passing  throiigh  the  pulmonary  artery  marks  the  place 
of  the  ductus  arteriosus  ;  a  similar  arrow-line  is  shown  passing  from  the 
inferior  vena  cava  through  the  fossa  ovalis  of  the  right  auricle  and  the 
foramen  ovale  into  the  left  auricle  ;  hv,  the  hepatic  veins  ;  vp,  vena  porta  ; 
X  to  vci,  the  ductus  venosus  ;  uv,  the  umbilical  vein  ;  ua,  umbilical  arteries  ; 
ve,  umbilical  cord  cut  short ;    ii',  iliac  vessels. 


PREGNANCY  AND  PARTURITION  1381 

With  the  first  breath  taken  by  the  new-born  child  all  the  mechanical 
conditions  of  the  circulation  arc  modified.  The  resistance  to  the  blood- 
flow  throii<^h  the  Iun<^s  bein^  dimiiii.sh<Hl,  the  bh)od  passes  from  the  pul- 
monary arteries  through  the  lungs  into  the  left  auricle.  The  pressure 
in  the  left  auricle  is  thus  raised,  while  that  in  the  right  auricle  falls, 
so  that  the  foramen  ovale  is  maintained  closed.  Even  before  birth 
prohferation  of  the  lining  membrane  may  be  seen  both  in  the  ductus 
arteriosus  and  in  the  ductus  venosus  ;  and  with  the  mechanical 
relief  of  the  vessels  afforded  by  respiration  and  the  changed  conditions 
of  the  foetus,  this  proliferation  goes  on  to  complete  obliteration  of  the 
vessels, 

PARTURITION 

As  the  uterus  increases  in  size  and  becomes  more  distended,  its 
irritability  becomes  greater,  so  that  it  is  easily  excited  to  contract. 
The  stimulus  may  be  supplied  from  adjacent  abdominal  organs, 
from  the  brain,  as  by  emotions,  or  by  direct  excitation  of  the  internal 
surface  of  the  uterus,  in  consequence  of  movements  of  the  foetus. 
In  many  cases  no  antecedent  stimulus  can  be  discovered,  and  the 
automatic  contraction  of  the  uterus  seems  to  be  analogoas  to  that  which 
occurs  in  the  distended  bladder.  These  contractions  ordinarily  give 
rise  to  no  sensations,  and  are  only  felt  when  they  are  augmented  in 
consequence  of  reflex  stimulation.  During  the  greater  part  of  preg- 
nancy they  have  little  or  no  effect  on  the  contents  of  the  uterus. 
During  the  last  weeks  or  days  of  pregnancy,  however,  these  contractions, 
which  have  now  become  more  marked,  have  a  distinct  physiological 
effect.  Not  only  do  they,  by  pressing  on  the  foetus,  cause  it,  in  most 
instances,  to  assume  a  suitable  position  for  its  subsequent  expulsion, 
but,  affecting  the  whole  body  of  the  uterus,  including  the  longitudinal 
muscular  fibres  surrounding  its  neck,  they  assist  the  general  enlarge- 
ment of  the  organ  in  dilating  the  internal  os  uteri,  so  that  the  upper 
part  of  the  cervix  is  obliterated  and  drawn  up  into  the  body  of  the 
uterus  some  little  time  before  labour  has  commenced. 

With  these  changes  in  the  uterus  are  associated  changes  in  the 
round  ligaments  and  in  the  vagina  and  vulva.  The  muscular  fibres  of 
the  round  ligaments  become  much  hypertrophied  and  lengthened,  and 
these  structures  can  therefore  aid  appreciably  the  uterine  contractions 
in  the  subsequent  expulsion  of  the  foetus.  The  vaginal  walls  become 
thickened  and  of  looser  texture,  so  as  to  afford  less  resistance  to  dis- 
tension during  the  passage  of  the  fo'tal  head. 

Considerable  discussion  has  taken  place  as  to  the  cause  for  the  onset 
of  the  processes  comprised  under  the  heading  of  labour  or  parturition  at 
a  nearly  constant  ])eri()d  of  two  hundred  and  seventy-two  davs  after 
conception.      Most  of  the  explanations  which   have  been  suggested. 


1382  PHYSIOLOGY 

such  as  the  great  irritability  of  the  uterus  at  the  termination  of  preg- 
nancy, the  loosening  of  the  foetal  membranes,  the  return  of  the  men- 
strual congestion  after  ten  months,  thrombosis  of  the  placental  sinuses, 
simply  replace  one  question  by  another.  According  to  Spiegelberg  the 
phenomena  accompanying  the  birth  of  twins,  which  are  often  born 
at  a  considerable  interval  from  each  other,  the  onset  of  contractions  of 
the  uterus  at  the  right  time  in  normal  as  well  as  in  extra-uterine 
foetation,  the  fact  that  the  extra -uterine  foetus  dies  when  it  has  become 
mature,  all  go  to  show  that  the  reason  why  labour  occurs  at  a  definite 
time  must  be  sought  for  in  foetal  rather  than  in  uterine  changes.  This 
author  suggests  that  some  substances  which  had  previously  been  used 
up  by  the  foetus  gradually  accumulate  in  the  maternal  blood  as  the 
foetus  becomes  mature,  and  provoke,  by  their  direct  action  on  the 
uterus  or  spinal  cord,  the  uterine  contractions  which  give  rise  to 
labour. 

Actual  parturition  is  in  man  generally  divided  into  two  stages.  In 
the  first  stage  the  contractions  are  confined  to  the  uterus,  and  chiefly 
act  in  dilating  the  os  uteri.  In  this  dilatation  two  factors  are  in- 
volved, namely,  the  active  dilatation  brought  about  by  the  contraction 
of  the  longitudinal  muscular  fibres  which  form  the  chief  constituent 
of  the  lower  part  of  the  uterine  wall ;  and  in  the  second  place,  a  passive 
dilatation  by  the  pressure  of  the  foetal  bag  of  membranes,  which  is 
filled  Math  amniotic  fluid,  and  forced  down  as  a  fluid  wedge  into  the 
OS  by  the  contractions  of  the  uterine  fundus.  The  uterine  contractions 
are  essentially  rhythmical,  being  feeble  at  first,  and  increasing  gradually 
in  intensity  to  a  maximum  which  endures  a  certain  time,  and  then 
gradually  subsides.  The  frequency  and  duration  of  the  contractions 
increase  as  labour  advances. 

As  soon  as  the  os  is  fully  dilated  and  the  foetal  head  has  entered 
the  pelvis,  the  contractions  change  in  character,  being  much  more  pro- 
longed and  frequent,  and  attended  by  more  or  less  voluntary  con- 
tractions of  the  abdominal  muscles.  This  action  of  the  abdominal 
muscles  is  associated  with  fixation  of  the  diaphragm  and  closure  of  the 
glottis,  so  that  pressure  is  brought  to  bear  on  the  whole  contents  of  the 
abdomen,  including  the  uterus.  No  expelling  force  can  be  ascribed 
to  the  vagina,  since  it  is  too  greatly  stretched  by  the  advancing  foetus. 
In  this  way  the  foetus  is  gradually  thrust  through  the  pelvic  canal, 
dilating  the  soft  parts  which  impede  its  progress,  and  is  finally  expelled 
through  the  vulva,  the  head  being  born  first.  The  membranes  generally 
rupture  towards  the  end  of  the  first  stage  of  parturition. 

A  third  stage  of  labour  is  generally  described.  This  consists  in  a 
renewal  of  uterine  contractions  about  twenty  to  thirty  minutes  after 
the  birth  of  the  child,  and  results  in  the  expulsion  of  the  placenta  and 
decidual  membranes. 


PREGNANCY  AND  PARTURITION  1383 

NERVOUS  MECHANISM.  We  possess  little  experimental  know- 
ledge of  tlie  nervous  niecliunism  of  parturition.  The  most  important 
observation  on  this  point  is  tlie  already  quoted  experiment  by  Goltz, 
in  which  this  physiologist  observed  the  normal  perforniance  of  menstrua- 
tion (heat),  impregnation,  and  parturition  in  a  bitch  whose  spinal 
cord  had  been  completely  divided  in  the  dorsal  region  during  the 
previous  year.  On  the  other  hand,  destruction  of  the  lumbo-sacral 
cord  completely  abolishes  the  normal  uterine  contractions  of  parturi- 
tion, so  that  this  act  must  be  regarded  as  essentially  reflex,  presided 
over  by  a  controlling  '  centre  '  in  the  grey  matter  of  the  cord.  The 
activity  of  the  centre  can  be  inhibited  or  augmented  by  impulses 
arriving  at  it  from  the  peripheral  parts  of  the  body,  as  by  the  stimu- 
lation of  sensory  nerves,  or  from  the  brain,  as  under  the  influence  of 
emotions.  The  nerve-paths  from  the  centre  to  the  uterus  have  been 
already  described. 


SECTION  V 
THE  SECRETION  AND  PROPERTIES  OF  MILK 

LACTATION 

During  pregnancy  the  foetus  obtains  the  whole  of  its  nourishment 
from  the  mother  by  means  of  the  placenta.  After  birth  the  quality  of 
the  nutriment  supplied  to  the  young  child  depends  on  the  activity 
of  the  cells  of  the  mammary  glands.  Now,  however,  nutrition  in- 
volves further  activity  on  the  part  of  the  young  animal,  the  alimentary 
canal  being  concerned  in  the  digestion  of  the  milk  supplied  by  the 
mother,  and  the  excretory  organs,  especially  the  kidneys,  being  made 
use  of  for  getting  rid  of  waste  material.  The  preparation  of  the 
mammary  glands  for  the  subsequent  nourishment  of  the  new-born  child 
begins  in  the  first  month  of  pregnancy,  and  is  marked  by  swelling  of  the 
glands,  rapid  proliferation  of  the  duct  epithelium,  and  production  of 
many  new  secreting  alveoli.  The  development  of  these  glands  in  the 
rabbit  has  been  already  described,  and  there  is  no  doubt  that  in  the 
human  species  the  process  follows  very  much  the  same  course,  being, 
however,  spread  over  nine  months  instead  of  four  weeks,  as  is  the  case 
wnth  the  rabbit.  During  the  latter  half  of  pregnancy  a  watery  fluid 
can  generally  be  expressed  from  the  nipple.  In  certain  mammals  this 
watery  secretion  gives  place  to  a  secretion  of  true  milk  at  the  end  of 
gestation  or  during  the  process  of  parturition  itself.  In  the  woman  the 
secretion  does  not  begin  as  a  rule  until  the  second  or  third  day  after 
birth,  though  the  formation  of  milk  may  be  anticipated  if  a  child  has 
been  put  to  the  breasts  during  the  latter  part  of  pregnancy.  Secretion 
begins  on  the  second  or  third  day,  even  if  the  child  has  been  born  dead 
and  no  attempt  at  suckling  has  taken  place.  For  the  maintenance 
of  the  secretion  the  process  of  suckling  is  absolutely  necessary.  If  the 
woman  does  not  nurse  her  child,  the  swelling  of  the  breasts  gradually 
passes  off,  the  milk  disappears,  and  the  glands  undergo  a  process  of 
involution.  Under  normal  conditions  the  secretion  of  milk  lasts  for 
six  to  nine  mojiths  and  may  in  rare  cases  extend  over  more  than  a 
year.  The  amount  secreted  increases  at  first  with  the  growth  and 
size  of  the  child.  The  following  Table  represents  the  average  amount 
of  milk  secreted  during  the  thirty-seven  weeks  after  birth.     It  will,  of 

1384 


THE  SECRETION  AND  PROPERTIES  OF  MILK       laJ^o 

course,  be  greater  with  strong,  big  children,  and  smaller  with  weakly 

children  : 

Increase 
Timo 
Ist  day     ..... 
2ii(l    ,." 

;{id 

■1th     „ 

5tli    „ 

Oth    „ 

7th    „ 

2nd  week  .... 

3rd-4th  week     .... 

oth-8th      , 

9th-12th     „       .  .  .  . 

13th-lGtli  „       .  .  .  . 

17th-20tli  „       .  .  .  . 

21st-24th  „       .  .  .  . 

25th-28th  „       .         .         .         . 


Decrease 


29th-32nd  week 
33rd-36th  „  . 
37th  week 


Milk  HC'crcted 

20 

gnu. 

97 

211 

326 

3G4 

402 

478 

502 

572 

736 

797 

836 

867 

,, 

944 

,, 

963 

" 

916 

grm. 

909 

„ 

885 

jj 

COLOSTRUM.  Before  the  secretion  of  true  milk  begins,  the  fluid 
which  is  obtain?d  from  the  breast  is  knowai  as  colostrum.  It  may  be 
expressed  from  the  breasts  immediately  after  birth  and  is  ingested  by 
the  child  during  the  first  two  days  after  birth.  The  colostrum  is  formed 
only  in  slight  quantities.  It  is  an  opalescent  fluid,  often  somewhat 
yellowish,  containing  fat  globules,  which,  if  the  fluid  be  allowed  to 
stand,  form  a  yellowish  layer  on  the  top.  Under  the  microscope,  in 
addition  to  the  fat  globules,  may  be  seen  the  so-called  colostrum 
corpuscles,  which  consist  of  multinucleated  cells  loaded  with  particles  of 
fat.  They  are  probably  leucocytes  or  phagocytes  which  have  wandered 
into  the  alveoli  and  have  taken  up  fat  globules.  Some  of  the  cor- 
puscles may  be  desquamated  secretory  cells.  Colostrum  is  distin- 
guished from  true  milk  by  containing  little  or  no  caseinogen.  It 
contains  about  .'5  per  cent,  of  proteins,  namely,  lactalbumen  and 
lactoglobulin,  which  coagulate  on  boiling.  Lactose  and  salts  are 
present  in  the  same  proportions  as  in  ordinary  milk.  It  is  popularly 
supposed  to  have  a  laxative  effect  on  the  child. 

PROPERTIES  OF  MILK 

Fully  formed  milk  presents  certain  features  whicli  are  common  to 

all  manuuals.     These  have  been  chiefly  studied  in  the  case  of  cows' 

milk.     We  may  therefore  deal  with  the  composition  of  cows"  milk 

and   point  out  latcM-  in  what  respects  jiuinan  milk  diiTcrs  thorotrom. 


1386  PHYSIOLOGY 

Milk  forms  an  opaque  white  fluid  with  characteristic  odour  and  sweetish 
taste.  Its  specific  gravity  varies  between  1028  and  1034.  Its  reac- 
tion to  litmus  is  neutral,  to  lacmoid  it  reacts  alkaline,  and  to  phenol- 
phthalein,  acid.  One  hundred  cubic  centimetres  of  fresh  milk,  when 
treated  with  lacmoid,  requires  41  c.c.  n/10  acid  for  neutralisation. 
When  treated  with  phenolphthalein  the  same  amount  requires 
19-5  njlO  alkali  for  neutrahsation.  When  exposed  to  the  air  milk 
rapidly  undergoes  changes  in  consequence  of  infection  by  micro- 
organisms. The  most  common  of  these  changes  is  the  formation  of 
lactic  acid  by  the  bacillus  lacticus.  In  some  cases  the  milk  may 
undergo  a  species  of  alcoholic  fermentation,  as  in  the  formation  of 
kephir,  which  is  made  by  the  fermentation  of  mares'  milk. 

The  opaque  appearance  of  milk  is  due  chiefly  to  the  presence  of 
multitudes  of  fine  fatty  particles.  On  allo^^^ng  the  milk  to  stand 
the  particles  rise  to  the  surface,  forming  cream,  and  by  a  mechanical 
agitation,  especially  if  the  milk  is  shghtly  sour,  they  may  be  caused 
to  run  together  with  the  formation  of  butter.  Much  discussion  has 
arisen  as  to  the  reason  why  the  fat  globules  do  not  run  together  natur- 
ally. By  many  authors  it  has  been  imagined  that  they  are  clothed 
with  a  special  protein  membrane  {haptogen  membrane)  originating  from 
the  protoplasm  of  the  cell  in  which  the  fat  globules  were  originally 
formed.  It  must  be  remembered  that  in  any  protein  solution,  such  as 
that  in  which  the  globules  are  suspended,  the  protein  tends  to  aggre- 
gate, with  the  formation  of  a  pellicle,  at  the  surface,  so  that  an  emulsion 
once  produced  in  such  a  fluid  will  tend  to  be  more  or  less  permanent. 
There  seems  therefore  no  reason  to  assume  the  presence  of  a  distinct 
membrane  differing  in  composition  from  the  proteins  present  in  the 
surromiding  fluid.  The  fats  of  milk  consist  for  the  greater  part  of  the 
neutral  glycerides,  tripalmitin,  tristearin,  and  triolein.  In  smaller 
quantities  it  contains  the  triglycerides  of  myristic  acid,  butyric  acid  (?), 
and  capronic  acid,  with  traces  of  caprylic,  capric,  and  lauric  acids. 

The  milk  plasma,  the  fluid  in  which  the  fat  globules  are  suspended, 
contains  various  proteins,  a  carbohydrate,  lactose,  and  inorganic  salts, 
with  a  small  amount  of  lecithin  and  nitrogenous  extractives. 

THE  PROTEINS  OF  MILK.  The  chief  protein  of  milk  is  caseino- 
gen,  belonging  to  the  class  of  phosphoprotcins.  Like  other  bodies  of 
this  class  it  presents  distinct  acid  characteristics,  being  precipitated 
by  acids  and  soluble  in  dilute  alkalies.  It  may  be  prepared  from 
separated  milk  by  the  addition  of  weak  acids.  A  convenient  method 
is  to  dilute  one  litre  of  milk  with  ten  litres  of  distilled  water  and  add 
to  the  mixture  10  c.c.  of  glacial  acetic  acid.  The  precipitate  which  is 
formed  rapidly  sinks  to  the  bottom  and  may  be  washed  two  or  three 
times  by  decantation.  It  may  be  purified  by  solution  in  dilute 
ammonia  and  precipitation  by  acetic  acid  two  or  three  times.     The 


THE  SECRETION  AND  PROPERTIES  OF  MILK       1387 

precipitate  finally  obtained  is  extracted  with  alcohol  and  ether,  and  the 
dried  caseinorren  prepared  in  this  way  forms  a  snow-white  powder 
which  is  practically  insoluble  in  water  and  dilute  salt  solutions.  It  is 
easily  dissolved  on  the  addition  of  a  little  alkali,  when  it  \nelds  solu- 
tions which  are  acid  to  htmus.  When  rubbed  up  with  chalk  it  dis- 
solves, displacing  the  carbonic  acid  and  forming  a  calcium  caseino- 
genate.  A  solution  of  caseinogen  in  soda  or  potash  is  transparent 
and  passes  easily  through  a  clay  cell.  The  calcium  caseinogenate 
forms  only  opalescent  solutions.  Apparently  the  compound  is  disso- 
ciated by  water  with  the  formation  of  caseinogen  acid  which  is  in  a 
state  of  partial  solution  as  swollen-up  aggregates.  It  is  impossible 
therefore  to  filter  calcium  caseinogenate  through  a  clay  cell.  It  is 
mainly  in  this  form  that  caseinogen  is  contained  in  milk,  hence  the 
opalescent  appearance  of  the  milk-plasma.  When  calcium  caseino- 
genate solution  is  boiled  it  forms  a  pellicle  on  the  surface  in  the  same 
way  as  milk  does.  On  treating  the  caseinogen  with  rennet  ferment  it 
is  converted  into  a  modification  known  as  paracasein,  which  in  the 
presence  of  lime  salts  is  thrown  out  as  insoluble  casein.  To  this 
process  is  due  the  clotting  of  whole  milk  by  rennet,  which  is  made  use 
of  in  the  preparation  of  cheese,  the  curd  consisting  of  a  network  of 
casein  enclosing  fat  globules  in  its  meshes.  On  allowing  the  clot  to 
stand  it  shrinks,  pressing  out  a  milk-serum. 

From  the  milk-serum  or  whey  may  be  obtained  two  other  proteins, 
known  as  Inctalhumen  and  ladoglobulin.  These  resemble  very  nearly 
the  albumen  and  globulin  of  blood-serum.  They  are  coagulated  on 
heating.  According  to  some  authors  a  third  protein  is  present  in 
the  whey,  to  which  the  name  whey-protein  has  been  given,  and  which 
is  supposed  to  be  split  off  from  the  caseinogen  under  the  action  of  the 
rennet  ferment. 

Milk  can  be  boiled  without  undergoing  any  coagulation.  If  it  be 
allowed  to  stand  and  become  sour  by  the  formation  of  lactic  acid,  at  a 
certain  period  boiling  the  milk  causes  its  complete  coagulation.  Later 
on  the  acid  produced  is  sufficient  in  itself  to  precipitate  the  caseinogen. 
Both  these  processes,  namely,  coagulation  of  half-sour  milk  by  heating, 
and  spontaneous  clotting  of  milk  by  the  production  of  acid,  are  made 
use  of  in  different  countries  for  the  manufacture  of  cheese. 

MILK  SUGAR.  The  sugar  of  milk,  or  lactose,  is  most  easily  ob- 
tained from  whey,  which,  after  separation  of  the  clot,  is  boiled  to  pre- 
cipitate the  remaining  proteins.  On  filtering  and  evaporating  slowly, 
the  milk  sugar  crystallises  out.  Lactose  is  a  disaccharide  and  has  the 
formula  CjoH220jj.  It  is  only  known  to  occur  in  milk.  It  may  be 
found  in  the  urine  of  nursing  women  when  tlie  breasts  are  not  kept 
empty,  so  that  there  is  reabsorption  of  the  lactose  formed  in  the 
mammary  glands.     It  is  unaltered  by  ordinary  yeast,  so  that  the 


1388  PHYSIOLOGY 

yeast  test  is  the  best  means  of  distinguishing  lactose  from  dextrose 
in  the  urine.  It  gives  the  ordinary  tests  for  reducing  sugar.  The  salts 
of  milk  include  insoluble  salts,  soluble  calcium  salts,  sodium  and 
potassium,  phosphates  and  chlorides. 

Mere  enumeration  of  the  constituents  of  milk  presents  but  little 
interest  unless  we  realise  how  closely  the  composition  of  this  fluid  is 
adapted  to  the  needs  of  the  gro^nng  animal.  In  the  first  place,  we 
find  a  proportionality  between  the  total  solids  of  the  milk  and  the 
rate  at  which  the  young  animal  grows.  It  must  be  remembered  that 
the  milk  taken  by  the  animal  serves  only  in  part  for  the  production 
of  energy  in  its  body,  a  great  proportion  of  it  being  required  for  the 
building  up  of  new  tissue.  In  no  respect  is  this  correspondence  seen 
better  than  in  the  comparative  analyses  of  the  ash  of  milk  and 
of  the  young  animal  of  the  same  species  which  were  made  by 
Bunge.  The  following  Table  shows  the  composition  of  the  ash  of  a 
rabbit  fourteen  days  old,  of  the  milk  which  it  was  receiving  from  its 
mother,  of  the  ash  of  rabbit's  blood  and  blood-serum.  Nothing  could 
be  more  striking  than  the  marvellous  way  in  which  the  cells  of  the 
mammary  gland  have  picked  out  from  the  salts  of  the  circulating 
plasma  exactly  those  salts  which  are  needed  for  the  growing  animal 
and  in  the  same  proportion  : 


Rabbit 

Rabbit's 

Rabbit's 

Rabbit's 

14  days  old 

milk 

blood 

blood-serum 

Potash   . 

10-8 

101 

23-8 

3-2 

Soda 

60 

7-9 

31-4 

54-7 

Lime 

350 

35-7 

0-8 

1-4 

Magnesia 

22 

2-2 

0-6 

0-6 

Iron  oxide 

0-23 

008 

6-9 

0 

Phosphoric  acid 

41-9 

39-9 

111 

30 

Chlorine 

4-9 

5-4 

32-7 

47-8 

This  close  correspondence  is  only  necessary  where  growth  is  very 
rapid,  so  that  the  greater  part  of  the  constituents  of  the  milk  have  to 
be  utilised  in  the  building  up  of  the  animal  tissues.  As  Bunge  has  shown, 
the  slower  the  growth  of  the  animal  the  greater  the  divergence  between 
the  composition  of  the  milk  and  that  of  the  new-born  animal.  We 
may  compare,  for  instance,  the  rabbit,  which  doubles  its  weight  in  six 
days,  with  the  dog,  which  doubles  its  weight  in  ninety-six  days,  and 
the  human  infant,  which  takes  one  hundred  and  eighty  days  to  double 
its  weight  at  birth. 

The  last  column  of  the  following  Table  represents  the  composition  of 
the  ash  of  cow's  milk,  and  shows  how  very  inefficiently  this  milk  can  be 
regarded  as  replacing  human  milk,  the  natural  food  of  the  infant. 


THE  SECRETION  AND  PROPERTIES  OF  MILK       1389 


Iiiraiit 

Kal>bit  14 

ilabhit's 

Puppy  ffiw 

Bitch's 

iM)ine 

Human 

Cow'b 

clays  old 

milk 

liouri  old 

iiijlk 

uiinuttti 
after  birth 

milk 

milk 

Potash 

10-8 

10- 1 

11-4 

150 

8-9 

35-2 

221 

Soda 

60 

7-9 

10-6 

8-8 

100 

10-4 

13-9 

Lime 

35  0 

35  7 

29-5 

27-2 

33-5 

14-8 

200 

Magnesia 

2-2 

2'2 

1-8 

1-5 

1-3 

2-9 

2-6 

Iron  oxide 

0-23 

0-08 

0-72 

012 

ro 

018 

0-04 

Phosplioric 

41-9 

39-9 

39-4 

34-2 

37-7 

21-3 

24-8 

acid 

Chlorine     . 

4-9 

5-4 

8-4 

16-9 

8-8 

19-7 

21-3 

The  fitness  of  caseinogen  for  building  up  the  tissues  of  the  body  is 
evident  when  we  compare  the  products  of  its  hydrolysis  with  those 
of  all  the  proteins  in  other  food-stuffs.  It  will  be  seen  that  practically 
every  amino-acid  and  allied  substance  employed  in  the  building  up 
of  the  various  proteins  is  represented  in  caseinogen.  The  only 
exception  is  glycine,  which  can  be  easily  formed  from  other  amino- 
acids. 

Chemical  Constitution   of   Different   Proteins 


_ 

.~ 

^ 

.^a 

a 

B 

s 

a 

a 

a 
1 

o 
"to 

i 

e 
w 

a 

3 

M 
O 

3 

o 
09 

a 

5 

a 
1 

EC 

i3 

a 
a 

3 

§ 
a 
< 

0 

2 

1 

3 

a 

A 

0 

Glycine 

0 

3-5 

0-4 

0-1 

10 

16-5 

36  0 

20 

Alanine 

4-19 

2-7 

2-2 

0-9 

2-0 

2-0 

2-5 

0-8 

21-0 

3-7 

Valine 

4-3 

+ 

10 

0-3 

10 

10 

0-9 

Leucine 

29  04 

20  0 

18-7 

10-5 

8-0 

5-6 

150 

21 

1-5 

111 

Isoleucine    . 

Phenyl- 

alanine    . 

4-24 

31 

3-8 

3-2 

3-7 

2-4 

3-2 

0-4 

1-5 

31 

Tyrosine 

1-33 

21 

2-5 

4-5 

1-5 

1-2 

1-5 

10-5 

2-2 

Serine 

7-8 

0-56 

0-6 

0-2 

0-5 

0-2 

0-4 

1-6 

Cystine 

0-31 

2-5 

0-7 

0-3 

0-5 

0 

Proline 

11-0 

2-34 

10 

2-8 

31 

3-2 

70 

5-4 

5-2 

+ 

5-1 

Uxyproline 

1-04 

0-2 

3-0 

Aspartie  acid 

4-43 

31 

2-5 

1-2 

5-3 

0-6 

4  0 

0-6 

+ 

41 

Glutamic  acid 

1-73 

7-7 

8-5 

110 

13-8 

37-4 

18-4 

0-9 

1->1 

Tryptophane 

+ 

+ 

+ 

lu 

+ 

+ 

0 

+ 

Arginine 

87-4 

5-42 

4-8 

101 

3-2 

7-6 

10 

71 

Lysine 

0 

4-28 

5-8 

4-3 

0  0 

2-8 

+ 

71 

Histidine 

0 

10-9o 

2-5 

2-5 

10 

0-4 

+ 

11 

Ammonia     . 

1-6 

2  0 

5-1 

0-4 

1-0 

In  another  point  we  find  an  adaptation  of  the  milk  to  the  growth 
of  the  young  animal,  and  that  is  in  its  lecithin  content.  Lecithin 
is  probably  employed  to  the  largest  extent  in  the  building  up  of 
the    central    nervous  system,   where   it   forms  the   most  important 


1390 


PHYSIOLOGY 


constituent  of  the  medullary  sheaths  of  the  nerve  fibres.  There  is  a 
corresponding  proportionality  between  the  lecithin  content  of  milk  and 
the  relative  brain  weight  of  the  young  animal.  Thus,  in  the  calf  the 
brain  is  only  -^  of  the  whole  animal.  In  cow's  milk  lecithin  is 
present  in  the  proportion  of  1-4  per  cent,  of  the  total  protein.  In 
the  puppy  the  brain  is  ^jj  of  the  whole  body  and  the  proportion  of 
lecithin  to  protein  in  the  milk  is  2-11  per  cent.  In  the  infant,  the 
brain  forms  ;  of  the  body  weight,  while  the  lecithin  is  3-05  per  cent, 
of  the  protein  of  human  milk. 


Calf 

Puppy 

Infant 

Relative  brain  weight  . 
Lecithin  content  of  milk  in  per- 
centage of  protein     . 

1  :  370 
1-40 

1  :  30 
211 

1  :  7 
3-05 

We  thus  see  that  under  normal  conditions  the  young  animal  is 
supplied  through  its  natural  food  with  all  the  food-stuffs  in  the  pro- 
portions which  it  requires  for  its  normal  nourishment  and  growth. 
It  is  impossible  therefore  satisfactorily  to  replace  the  natural  milk 
of  an  animal  by  that  of  another  species.  In  civilised  communities 
it  is  becoming  more  and  more  the  custom  to  endeavour  to  feed  the 
child  with  cow's  milk,  more  or  less  modified,  in  the  vain  endeavour  to 
reproduce  the  properties  of  human  milk.  Among  all  classes  this 
involves  the  administering  of  a  milk  differing  in  its  quahties  and  in  the 
relative  proportions  of  its  proteins,  its  fats,  carbohydrates,  and  salts, 
from  human  milk.  So-called  '  humanised  '  milk  is  only  a  rough  imita- 
tion of  the  natural  mother's  milk.  Among  the  poorer  classes  ihis  arti- 
ficial feeding  means  the  replacement  of  a  natural  sterile  food,  throwing 
very  httle  work  on  the  digestive  organs  of  the  child,  wuth  a  foreign  milk, 
very  difl&cult  to  digest,  and  often  teeming  with  micro-organisms. 
There  is  no  doubt  that  of  the  children  dying  during  the  first  year  of 
fife  four-fifths  are  murdered  by  this  unnatural  method  of  feeding.  In 
some  cases  it  is  necessary  to  adopt  artificial  feeding  because  the  mother 
is  abnormal,  and  there  is  an  insufficient  secretion  of  milk.  It  is  there- 
fore important  to  know  what  are  the  main  differences  in  composition 
between  human  and  cow's  milk.  In  human  milk  the  caseinogen 
is  not  only  absolutely  but  also  relatively  less  than  in  cow's  milk, 
while  the  latter  is  relatively  poorer  in  milk  sugar.  Human  milk 
is  poorer  in  salts,  especially  in  lime,  containing  only  one-sixth  of 
the  amount  present  in  cow's  milk.  Human  milk  is  also  said  to  be 
poorer  in  citric  acid.  The  main  differences  may  be  summarised  as 
follows  : 


THE  SECRETION  AND  PRDPERTIES  OF  MILK 


I  .".91 


Water 

I'roieiiis 

Fat 

Milk  bugar 

Salts 

Caseinogen 

Albiunin 

Human  milk 

Cow's  milk    . 

88-5 
S7-1 

1-2 

0-5 

o-r.:j 

3-3 

1 
(50            0-2 

IS             (CT 

The  caseinofijen  of  human  milk  presents  several  points  of  difference 
from  the  caseinogen  of  cow's  milk.  It  is  less  easily  precipitated  by 
acids.  When  coagulated  by  rennet  it  does  not  form  a  firm  clot,  but  is 
thrown  out  in  a  flocculent  form.  It  is  thus  much  more  susceptible  to 
the  action  of  gastric  juice.  Whereas  the  caseinogen  of  cow's  milk 
generally  gives  a  precipitate  of  *  pseudonuclein  '  on  digestion  with 
pepsin  and  hydrochloric  acid,  a  smaller  or  no  precipitate  is  formed 
with  human  caseinogen. 

Another  important  advantage  of  human  milk  for  the  infant  hes  in 
the  presence  of  antitoxins.  It  has  been  shown  by  Ehrlich  that  when 
a  female  animal  has  been  immunised  against  any  toxin  and  has  pro- 
duced in  consequence  antitoxins  in  its  blood,  these  antitoxins  will, 
if  it  has  young,  pass  over  into  the  milk.  The  same  passage  of  anti- 
bodies into  the  milk  has  been  proved  in  the  case  of  various  infective 
disorders.  The  ingestion  of  human  milk  will  therefore  not  only 
nourish  the  infant,  but  will  provide  it  with  a  certain  measure  of  passive 
immunity  against  possible  infection  by  diseases  to  which  its  species  is 
liable. 

THE  SECRETION  OF  MILK.  When  fully  formed,  each  mam- 
mary gland  consists  of  fifteen  to  twenty  lobes  connected  by  connective 
tissue.  Each  lobe  is  made  up  of  a  mass  of  secreting  alveoli  which  lead 
by  narrow  ducts  into  one  large  lactiferous  duct.  These  lactiferous 
ducts,  one  from  each  lobe,  open  on  the  nipple,  undergoing  in  the  nipple 
itself  an  oval  enlargement.  Before  secretion  begins  the  alveoli  as  well 
as  ducts  are  lined  with  a  cubical  epithelium.  When  secretion  com- 
mences a  marked  dift'erence  develops  between  the  epithelium  of  tiie 
alveoli  and  that  of  the  ducts.  While  the  latter  retains  its  previous 
character,  the  cells  of  the  secreting  epithelium  grow  in  length  and  pro- 
ject into  the  lumen  of  the  gland.  In  the  innermost  part  of  the  proto- 
plasm numerous  fat  globules  make  their  appearance.  If  sections 
be  made  of  the  gland  during  the  various  stages  of  its  activity  and 
stained  by  Altmann's  method  (acid  fuchsin  and  picric  acid),  it  will 
be  seen  that  the  commencement  of  activity  is  marked  by  the  growth 
of  the  innermost  part  of  the  celLs  and  the  development  in  these  of 
a  number  of  granules  (Fig.  5(14).  These  granules  fijially  lengthen 
into  shapes  like  spirilla,  while  others  of  them  form  fat  and  become 


1392 


PHYSIOLOGY 


metamorphosed  into  fat  granules.  The  nuclei  of  the  cells  also  divide, 
apparently  in  preparation  for  the  replacement  of  some  cells  which 
undergo  complete  degeneration  and  are  cast  off  into  the  secretion. 

We  know  very  little  about  the  mechanism  of  milk  secretion.  It 
seems  impossible  at  present  to  explain  the  very  close  adaptation 
between  the  activity  of  the  secretory  cells  and  the  needs  of  the  infant 
or  young  animal.  Two  at  least  of  the  constituents  of  milk,  caseinogen 
and  lactose,  are  peculiar  to  this  secretion.  It  has  been  assumed  that  the 
caseinogen  is  produced  by  some  sort  of  alteration  in  the  nucleo-proteins 


Fig.  564.  Sections  of  mammary  gland  of  guinca-jjig  (fat-granules 
stained  black  with  osmic  acid). 
A, during  rest.  B,  during  active  secretion.  It  will  be  noticed  that  in  this 
case  the  active  formation  of  products  of  cell-metabolism  (granules,  &c.)  begins 
with  the  commencement  of  secretion,  and  does  not  occur  almost  exclusively 
during  rest,  as  in  the  salivary  glands.  In  the  mammary  gland,  the  active 
growth  of  protoplasm,  the  formation  of  granules  from  the  protoplasm,  and 
the  discharge  of  these  granules  in  the  secretion  appear  to  go  on  at  one  and 
the  same  time. 

of  the  gland-cells,  and  that  the  lactose  is  derived  in  the  same  way  from 
some  sort  of  gluco-protein  or  gluco-nucleoprotein,  but  the  evidence  for 
either  of  these  assumptions  is  very  scanty.  The  growth  of  the  mam- 
mary glands  during  pregnancy  is  largely  determined  by  some  form  of 
chemical  stimulation,  the  specific  hormone  being  produced  first  in  the 
ovary  and  secondly  in  the  growing  foetus.*  It  has  been  suggested  by 
Hildebrandt  that  this  stimulus  is  inhibitory  in  character — inhibitory, 
that  is  to  say,  of  secretion — and  therefore  tending  to  the  continuous 
growth  of  the  gland-cells.  With  the  removal  of  the  foetus  at  birth  the 
source  of  the  inhibitory  stimulus  is  removed  and  the  overgrown  gland- 

*  But  see  p.  1363. 


THE  SECRETION  AND  PROPERTIES  OF  MILK       1393 

cells  enter  into  a  condition  of  spontaneoiLS  activity.  However  this  may 
be,  there  is  no  doubt  that  the  secretion  of  the  gland,  once  formed,  is 
continued  independently  of  the  foetus,  or  indeed  of  any  of  the  pelvic 
organs.  The  onset  of  a  new  pregnancy  brings  the  secretion  to  a  close. 
Removal  of  the  ovaries  in  a  cow  is  sometimes  employed  as  a  means  of 
prolonging  the  secretion  of  milk.  The  only  condition  which  is  neces- 
sary for  secretion  to  continue  during  six  to  nine  months  after  birth 
is  the  repeated  emptying  of  the  gland,  i.e.  the  removal  of  the  secreted 
milk.  The  process  of  suckling  not  only  removes  the  milk  already 
secreted  but  excites  the  secretion  of  more  milk.  The  secretion 
is  certainly  subject  to  nervous  influences,  but  physiologists  have 
not  succeeded  in  either  producing  secretion  by  stinmlation  of  the 
nerves  going  to  the  glands,  or  in  stopping  secretion  by  section  of  these 
nerves.  Moreover  the  food  of  the  animal  may  be  varied  within  very 
wide  limits  without  altering  the  composition  or  amount  of  the  milk 
secreted,  provided  only  that  the  food  is  sufficient  in  amount.  The  only 
constituent  of  the  milk  for  which  we  have  direct  evidence  of  alteration 
by  changes  in  the  food-supply  of  the  mother  is  the  fat.  It  is  well 
known  that  the  composition  of  butter  may  be  affected  according  to  the 
food  supplied  to  the  cow.  A  large  supply  of  oilcake,  for  instance,  may 
result  in  the  production  of  a  butter  which  is  deficient  in  the  higher  fatty 
acids  and  is  therefore  oily  at  ordinary  temperatures.  Abnormal  fats 
and  fatty  acids,  such  as  iodised  fats  or  erucic  acid,  when  administered 
to  an  animal  in  lactation  may  appear  among  the  fats  of  the  milk. 
Not  only  can  the  secretion  and  composition  of  the  milk  be  affected 
reflexly  through  the  nervous  system,  as,  e.g.  under  the  influence  of 
emotions,  but  the  influence  may  be  reciprocal.  This  is  especially  marked 
in  the  case  of  the  pelvic  organs.  The  act  of  suckling  excites  tonic  con- 
tractions of  the  uterus.  Pm-ring  the  child  to  the  breast  shortly  after 
birth  is  therefore  an  important  means  of  causing  contraction  of  the 
uterus  and  stopping  any  tendency  to  ha)niorrhage  from  the  venous 
sinuses  opened  by  the  separation  of  the  placenta  and  foetal  membranes. 
The  nursing  of  her  child  is  therefore  an  important  means  of  procur- 
ing a  proper  involution  of  the  uterus  after  labour.  Many  uterine 
troubles  among  women  may  be  ascribed  to  the  previous  neglect  of  this 
elementary  duty. 


88 


iM)i:x 


Abdominal  respiration,  1105 

effect  on  blood  pressure,  105G 
Abrin,  1153 

Absinthe,  action  of,  498 
Absorption  in  large  intestine,  813 

of  amino-acicLs,  840-845 

of  carbohydrates,  838 

of  fats,  832 

of  foodstuffs,  826-850 

of  proteins,  839 

of  water  and  salts,  826 

significance  of  lipoids  in,  829 
Absorption-coefficient  of  gases,  1179 
Acapnia,  1228 

Accelerator  nerves  of  heart,  1094 
Accessory  olive,  415,  431 
Accommodation,  594,  599 

changes  in,  607,  013 

comparative  physiology  of,  009-612 

mechanism  of,  606 

range  of,  608 
Acetamide,  53 
Acetic  acid,  53,  59 
Acetins,  58 

Aceto-acetic  acid,  detection  of,  1256 
Acetone,  53 

bodies  in  urine,  1255 

in  diabetes,  896 
Achromatic  spindle,  1348 
Achroodextrin,  75.  741 
Acid  albumin,  109 

amides,  53 

hydrolysis  of  proteins,  83,  84 

number  of  fats.  61 
Acidosis,  805 

in  diabetes,  896 
Acids,  organic,  52 
Acromegaly,  1331 
Acrosc,  67 

synthesis  of,  170 
Acrylic  series,  60 
Action-current,  E.M.F.  of,  262 
Activity,  optical,  56 
Adaptation,  5 

muscular,  197 

sensory,  538 

visual,  639 
Addison's  disease,  1322 
Adenine,  114.  878 
Adipose  tissue,  58 

action  of  gastric  juice  on,  771 

of  ])ancreatio  juice,  793 
Adrenalin,  55,  1322 

action  on  blood  pressure.  1 323 


Adrenalin,  action  on  nerve  terminations, 
314 

and  sympathetic  S3^stem,  1323 

instability  of,  1324 

isomers,  action  of,  1323 
Adsorption,  by  colloids,  157 

by  globulin,  165 

in  ferment  action,  187 

law  of,  164 

of  toxins,  1156 
Adventitia  of  artery,  981 
Aerotonometers,  1180,  1192 

specific  surface  of,  1193 
Afferent  autonomic  fibres,  531 

impulses  from  muscles,  389 

nerves,  285 

path,  370 

tracts,  cerebellum,  453 
cerebrum,  477 
After-images,  637 

coloured,  643.  649 
After-load,  227 
Air,  composition  of,  1173 

expired,  1173 
Alanine,  53,  86,  90 

deamination  of,  171 
Albuminates,  109 
Albuminoids,  118 
Albumins,  characters,  108 
Albuminuria,  1253 
Albumoses,  111,  770 
Alcaptonuria,  870,  1256 
Alco-gels,  155 
Alcohol,  food-value  of,  724 
Alcohols,  50 

polyatomic,  51 
Aldehyde.  51 

reactions  of,  51,  52 

resin,  52 
Aldehydes,  polymerisation  of.  52 
Aldol,  133,  889 

condensation,  133 
Aldoses,  65 
Alexia,  514 
Alkali  albumui.  109 
Alkaline  luematin,  937 
Allantoin.  879 
Allied  reHexes,  385 
'  All  or  none  '  phenomenon,  2.30 
Alloxan.  879 
Altitude,  effect  of.  on  red  corpuscles,  1229 

on  respiration.  1207 
^////i/j/iw'tf  granules,  18 
Aluminium,  48 
1395 


1396 


INDEX 


Alveolar  air,  carbon  dioxide  in,  1206 

composition  of,  1175 

sampling  of,  117-1 
Alveoli.  1163 
Amacrine  cells,  625 
Amboceptors,  1159 
Amide  nitrogen  of  proteins,  101 
Amines,  54 

action  of,  1325 

formed  in  putrefaction,  173.  1325 
Amino-acids,  53,  85 

absorption  of,  840-845 

aromatic,  93 

esters  of,  89 

fate  after  absorption,  845 

food-value  of,  722 

heat  equivalents  of,  862 

in  digestion,  739 

interconvertibnity  of,  864 

separation  of,  88 

sulphur  in,  95 

synthesis  of,  129,  172 
Amino-isobutj-l  acetic  acid,  90 
a-amino-glutaric  acid,  91 
a-amino-succinic  acid,  91 
a-amino-thiopropionic  acid,  96 
Ammonia,  estimation  in  urine,  1260 

production  from  amino-acids,  860 
in  acidosis,  865 
in  muscle,  245 
Ammonia -nitrogen  of  proteins,  101 
Amoeba,  14 

Amoeboid  movement,  277 
Amphoteric  electrolytes,  88,  165 
Ampulla  of  semicircular  canal,  676 

stimulation  of,  679 
Amylase,  75 

of  pancreatic  juice,  793 
Amyloid  substance,  117 
Amj'loplasts,  75 
Amylopsin,  793 
Anacrotic  pulse,  1042 
Anaemia,  1131 
Anaerobic  organisms,  27 
Analgesia,  552 
Anal  sphincter,  825 
Anaphase  of  mitosis,  1348 
Anarthria,  513 
Anelectrotonus,  298 
Anisotropous  substance,  203 
Aiakle  clonus,  379 
Anodal  contraction,  295 
Anode,  208 
Ancestrum,  1371 
Anterior  cerebellar  tract,  401,  417 

commissure,  482 
Antidromic  fibres,  365 

of  Bayliss,  1124 
Antigens,  1158 
Antiiysins,  1155 

Anti-peristalsis  in  large  intestine,  823 
Antithrombin.  9.34 
Antitoxins,  166,  956,  1154 
Antipeptone,  790 
Apex-beat,  1018 
Aphasia,  512 
Apncea,  1205,  1222 


Apnoea  spuria,  1223 

vagi,  1222 

vera,  1222 
Aqueduct  of  S3'lvius,  409,  421 
Arabinose,  66 
Arachidic  acid,  59 
Arbeitssammler,  249 
Archipallium,  471 
Arcuate  fibres,  414 
Arginase,  866 
Arginine,  92,  93,  100 
Aristotle's  experiment,  550 
Aromatic  compounds,  54 

substances,  fate  of,  869-873 
'  Arrest '  curves,  224,  233 
Arterial  pressure,  983,  986 

and  cardiac  output,  997 

in  man,  987 
Arteries,  distensibility  of,  982 

flow  in,  1034-1049 

structure  of,  981 
Arterioles,  structure  of,  981 
Arytenoid  cartilage,  578 

muscle,  581 
Ascending  tracts,  434 
Ash,  estimation  in  food,  680 
Asparagine,  91 

food-value  of,  723 
Aspartic  acid,  91,  100 
Aspergillus  oryzse,  187 
Asphyxia,     blood- pressure    changes     in 
1105 

factors  in,  1106-1108 

in  decerebrate  animal,  1107 

stages  of,  1204 
Assimilation,  4,  26 
Association  areas,  511 

cells  of  cortex,  483 

centres,  488 

fibres  of  cerebrum,  481 

sensory,  509 
Astasia,  456 
Asthenia,  456 
Astigmatism,  598 
Asymmetric  carbon  atoms,  50 
Ataxy,  391,  669 
Atonia,  456 
Attraction  sphere,  17 
Ativater-Benedict  calorimeter,  696 
Auditory  area,  505 

fatigue,  576 

localisation,  577 

nerve,  nucleus  of,  427,  428 

ossicles,  571 

mechanics  of,  572 

projection,  577 

radiation,  479 

sensations,  562 

analysis  of,  575 
Audito-sensory  area,  488 
Auerbach's  plexus,  523,  529 

in  intestine,  functions  of,  818,  819 

in  stomach,  784 
Aurse  in  epilepsj%  497,  503 
Auricle,  pressure-changes  in,  1015 
Auriculo-ventricular  bundle,  1006,  1072 
node,  1072 


INDEX 


1397 


Autonomic  fibres,  afferent,  5IU 

cranial,  527 

of  vagus,  528 

sacral,  528 

system,  classification  of,  525 
Autonomic  nervous  system,  520-532 
Autoxidisable  sxibstances,  1234 
Average  error  method,  540 
Avogudro's  hypothesis,  139 
Axis  cylinder,  280 
Axon.  280 

reflexes,  529 

-  in  vaso-dilator  fibres,  1125 


BAfTERiA,  action  on  amino-acids,  84 

of  putrefaction,  173 
Bacterium  nitromonas,  43 
Bahnung,  344 

in  cortex,  499 
Balanced  reactions,  185 
Balance-sheets  of  body,  685 
Barcroft's  blood-gas  apparatus,  1177 
Barometric  pressure,  influence  on  alveolar 

COo.  1207 
Basal  ganglia,  definition  of,  425 

development,  410 
Basophile  leucocytes,  919 
Basilar  membrane,  functions  of,  574 
Bathmotropic  effect  of  vagus  excitation, 

1091 
Bayliss  and  Starling  on  intestinal  move- 
ments, 818 

on  depre  sor  reflexes,  1097,  1127 

on  secretin,  797 
Beats,  565 

Bechterew's  nucleus,  429,  454 
Bcckmami's  apparatus  for  f  reezirig-poiut, 

143,  144 
Behenic  acid,  59 

Bell  and  Magendie's  law,  285,  365 
Benedict's  respiration  apparatus,  690 
Bensley  on  islets  of  Langerhans,  802 
Benzene  ring,  54 

origin  of,  131 
Benzyl  alanine,  172 

pyrotartiiric  acid.  172 
Bernard's    experiment     on     vaso-motor 

nerves,  1103 
Belz  cells,  484 
Bichromate  cell,  208 
Bidder's  ganglion,  1058 
Biedernuinn^s  fluid,  235 
Bile.  803-807 

acids.  84 

composition  of,  804 

flow  of,  805 

functions  of,  806 

pigment,  origin  of.  943 

salts,  804 

circidation  of.  807 

effects  of.  on  lipase  action,  794 

functions  of.  80() 

secretion  of.  805 
Biliary  fistula.  804 
Biinoleeular  reaction.  181 
Binocular  vision,  656,  ()62 


P,ingen.  21 

Biophor,  21 
Biuret.  1246 
base,  98 

reaction,  102,  111 
Bladder,  afferent  impulses  from,  1293 
central  control  of,  1296 
evacuation  of,  1294 
filling  of,  1293 
innervation  of,  1292,  1295 
musculature,  1290 
rhythmic  contractions  of,  1294 
sphincters  of,  1290,  1297 
Blind  spot,  626 
BUx  apparatus.  220 
Blood,  915-978 

alkalinity  of,  1190 
amount  in  body,  964 
carbon  dioxide  in,  1186,  1195 
coagulation.  917,  947-963 
effect  of  calcium  on,  949 
historical  account,  959-963 
negative  phase,  956 
positive  phase,  956 
corpuscles,  relative  amount,  967 
electrical  conductivity,  972 
freezing-point  of,  972 
gases  of,  1177 
gas  determination,  chemical  methods, 

■  1177 

pumps,  1175 
general  composition  of,  973 
hemolysis,  25,  141,  926,  943,  1131, 

1159 
hydrogen  ion  concentration  of,  1213 
laking  of,  926 
life-history  of  red   corpuscles,  939- 

943 
methods  of  preventing  coagulation, 

947 
osmotic  pressure  of,  972 
oxygen  capacity  of,  965,  969 
pigments,  927 

synthesis  of,  937 
plasma,  coagulation  of,  948 
composition  of,  973 
proteins  of,  955 
relative  amoimt,  967 
platelets,  944-946 
pressure,  alterations  of,  997 
a])paratus.  984 
in  capillaries,  1048 
in  man.  9S7 

in   vascular  system,   985,   986- 
998 
reaction  of.  971 
reactions  of.  1190 
rod  corpuscles,  916.  92-1-943 
chemistry  of.  926 
destniction  of.  940 
effect  of  altitude  on  number, 

1229 
enumeration  of,  968 
life  ..f.  942 

osmotic  ])ro]>erties  of.  925 
regeneration  of.  941 
stroma,  927 


1398 


INDEX 


Blood,  reducing  substances  in,  1212 

serum,  conditions  of  proteins  in,  977 

proteins  of,  976 
specific  gravity  of,  970 
variations  in  amount  of,  1129-1132 
velocity  of,  999-003 
vessels,   nervous   control   of,    1103- 

1128 
volume,  carbon  monoxide  method, 

965 
white  corpuscles,  918-923 
Body  as  a  machine,  4 

temperature,  diurnal  variations,  1308 
regulation  of,  1305-1316 
Bone-marrow,  structure  of,  920  939 
Boundary  layer,  1264 
Bowman's  capsule,  1265 
Bowman's  glands,  559 
Boyle's  law,  137 
Brachium,  superior,  424 
Brain,  407 

development  of,  408 
evolution  of,  411,  434 
stem,  ascending  tracts,  434 
association  areas  of,  511 
cortical  areas,  494 
descending  tracts,  438 
evolution  of,  408 
functions  of,  431-434,  4tl-446 
long  paths  in,  431 
structure  of,  407-440 
Break  contraction,  215 
excitation,  296 
induction  shock,  211 
Broca's  aphasia,  512 
convolution,  492 
Brodie's  perfusion  apparatus,  1082 
Bro7nine,  48 
Bronchi,  1163 
Bronchial  murmur,  1169 
Bronchioles,  1163 
BrowTiian  movement,  161.  162 
Bruits,  cardiac,  1022 
Bulbo-spinal  animal,  442 
Bulbo-spiral  fibres  of  heart,  1005 
Bundle  of  His,  1006,  1072 
BurrKs  capillary  electrometer,  255 
B urdon- Sanderson' s  electrodes,  251 
Bnrdaclis  column,  366,  397,  401 
Biltschli's  emulsion  theory,  19 
Butyric  acid,  53,  59 

Cadaverine,  173 
Caffeine,  115,  875 

diuretic  action  of,  1275 
Calcium  salts,  47 
Calcium  salts,  in  milk  coagulation,  772 

effect  on  heart,  1080,  1093 

excretion  of,  815 

excretion  in  large  intestine,  815 

function  in  blood  coagulation, 
949 

phosphate  in  urine,  1257 

in  starvation,  700 
Calculi,  biliary,  51 
Callender  recorder,  248 
Calorific  value  of  diet,  728 


Calorific  value  of  food-stuffs,  694 
Calorimeter,  3 

Atwater-Benedict' s,  696 
Canal  of  Schlemm,  604 

functions  of,  666 
Cane  sugar,  73 

inversion   of,  in   stomach,  768, 
772 
Cannon's  shadow  methods  for  movements 
of  alimentary  canal,  759,  782,  817 
Capillary  circulation,  1046-1049 
electrometer,  193,  254 

tracings,  analysis  of,  258 
pressure,  1048 
wall,  permeability  of,  1135 
.  Capric  acid,  59 
Caprylic  acid,  59 
Caproic  acid,  59 
Caput  cornu  posterioris,  358 
Carbamide,  see  Urea 
Carbamino-acids,  88 
Carbohydrate  metabolism,  899-914 

in  starvation,  702 
radical  in  proteins,  104 
Carbohydrates,  action  of  gastric  juice  on, 
772 
influence  of,  on  metabolism,  711 
Carbohydrates,  49,  64 
absorption  of,  838 
imbibition  by,  169 
synthesis  of,  40,  41,  122 
Carbon  assimilation,  121 

importance  of,  39 
Carbon  tetrahedron,  56 

dioxide,  assimilation  of,  121 
in  atmosphere,  41 
condition  of,  in  blood,  1186 
constancy    of,    in    alveolar    air, 

1206 
excretion  of,  1172 
tension  in  alveoli,  1195 
tension  in  blood.  1188,  1195 
tensions  in  tissues,  1186 
Carbonic  oxide  hiemochromogen,  935 
hfemoglobin,  929,  931 
Cardiac  cycle,  sequence  of  events,  1008 

time  relations,  1023 
Cardiac  impulse,  1018 
murmurs,  1021 

muscle,   factors    modifying    activity 
of,  1077-1084 
influence  of  tension  on,  1077 
physiological       properties      of, 
1074-1077 
nerves,  1087 
output,  1026-1031 
sound,  1010 
Cardinal  points  in  schematic  eye,  591 
Cardiogram,  1019 
C!ardiograph,  1018 
Cardio-inhil)itory  centre,  1095 
Cardiometer,  1029 
Cardio-pneumatic  movements,  1025 
Carlson  on  heart  of  limuhis,  1064 
Carotid  gland,  1334 
Casein,  formation  of,  772 
hydrolysis  of,  89 


INDEX 


1399 


Caseinogen,  100,  111 

action  oi  gastric  juice  on,  772 

preparation  of.  1380 
Catacrotic  pulse,  1042 
Catalase,  1237 
Catalysers,  177 
Catalysis,  177 

as  a  surface  phenomenon,  179 

by  formation  of  intermediate   pro- 
ducts, 179 

of  methj'l  acetate,  185 

theories  of,  179 

velocity  of,  180,  181 
Catechol,  55 
Catelectrotonus,  298 

Cathcart  on  carbohj'drate  metabolism,  907 
Cathodal  contraction,  295 
Cathode,  208 
CeU,  13 

sap,  14 

structure  of,  16 

waU,  14,  23 

composition  of,  23 
electrical  phenomena  in,  193 
permeability  of,  24,  25,  140 
Cells,  chemical  changes  in,  170 

galvanic,  see  Galvanic  cells 

growth  of,  1341 

histological  differentiation  of,  7,  35 

synthesis  in,  188 

vital  phenomena  of,  26 
Cellulose,  76,  724 

digestion  of,  813 

food-value  of,  724 

hydrolysis  of,  77 
Central  nervous  system,  324,  532 

segmentation,  368 
Centres  in  medulla,  443 
Centro -acinar  cells,  799 
Centrosome,  17,  20,  36 
Cephalin,  62 
Cetyl  alcohol,  51,  61 
Cerebellar  ataxy,  457 

gait,  457 

path,  437     - 
Cerebello-olivary  fibres,  416 
Cerebellum,  ablation  of,  455 

afferent  tracts,  453 

corpus  dentatum,  420 

efferent  tracts,  454 

functions  of,  447 

Golgi  cell,  452 

inferior  peduncles,  414,  417,  453 

middle  peduncle,  453 

nucleus  emboliformis,  420,  438 
fastigii,  420,  43H 
globosus,  420,  438 

Purkiiije  cells,  451 

roof  nuclei,  420,  431,  438,  453 

stimulation  of,  455 

structure  of.  451 

superior  peduncles,  438,  4.")4.  478 

vermis.  420.  451 
Cerebral  axis,  intermediate  grey  matter. 
430 

cortex,  associative  functions,  ."MIO 
excitability  of,  493 


Cerebral  cortex,  function  of  layers,  488 
lamination  of,  483,  486 
motor  areas  in,  494 
sensory  areas  in.  501 
structure  of,  470.  483 
thickness  of,  487 
hemispheres,  470-519 
development  of,  470 
functions  of,  491-519 
tracts  in,  477 
localisation,  historical,  491 
vesicles,  334 
Cerebrum,  afferent  tracts  of,  477 
association  fibres.  481 
commissural  fibres  in,  477 
development  of,  408 
fissures  of,  473 
lateral  ventricles,  473 
lobes  of,  473 
projection  fibres.  477 
structure  of,  470-490 
Cerumen,  569 

'  Characteristic  '  of  excitability,  295,  305 
Chemical  changes  in  cells,  170 

in  living  matter,  170- 

188 
in  muscle,  237-245 
correlation  of  functions.  1317 
stimulation  of  muscle,  207 
Chemiotaxis,  6,  29,  555 
in  leucocytes,  1149 
Cheyne-Stokes  breathing,  1223 
Chitin,  70 
Chlorides,  estimation  of,  in  urine,  1262 

resorption  of,  in  kidney,  1285 
Chlorine,  47 

Chlorophyll,  4,  7,  17,,40,  41,  122,  936 
Chloroplasts,  17,  36 
Cholesterol,  51,  61,  62 
Choline,  62 

structure  of,  63 
Chondroitin,  117 
Chondroitin-sulphuric  acid,  117 
Chondromucoid.  117 
Chorda  tjinpani.  527.  746 

vaso-dilator  fibres  of,  1121 
Choroid  coat,  603 

plexus,  423 
Chromaffine  substance,  1321 
Chromatic  alK-rration,  597,  636 
Chromatin.  16,  17.  33 
filaments,  16 
granules,  15 
Chromatolysis,  361 
Chromophile  substance,  1321 
Chromoproteins.  112 
Chromosomes.  17.  33,  34 

number  of,  in   somatic   cells,  1348 
1349 
Chronograph.  217.  218 
Chroncjtropic  effect  of  vagus  excitation, 

1091 
Chyle.  1134 

fat  in.  833 
Ciliary  ganL'lion.  615 
movement,  277 
muscle.  606 


1400 


INDEX 


Ciliary  nerves,  615 

processes,  603 
Ciliated  epithelium,  277 
Cilio-spinal  centre,  617 
Cingulum,  473,  481 
Circulating  proteins,  718 
Circulation,    general    features    of,    979- 
985 

in  amphibia,  979 

in  fishes,  979 

foetal,  1379 

influence  of  gravity  on,  996 

in  lungs,  1053-1056 

in  mammals  and  birds,  980 

physiology  of ,  979-1132 

effect  of  respiration  on,  1054 

schema,  994 

time,  1030 
Clarke's  column,  359,  398,  401,  403,  437 
Climacteric,  1361 
Climate,  influence  of,  on  diet,  732 
Clonus,  268 
Closing  tetanus,  308 
Clostridium  'pasteuriamnn,  44 
Coagulation  of  blood,  917,  947-963 

of  colloids,  79,  166,  167 

of  mUk,  772 

of  proteins,  79,  105,  108-109 

reversible,  79 
Coccygeal  ganglion,  522 

gland,  1334 
Cochlea,  573 

development  of,  674 
Cochlear  canal,  574 

nerve,  nucleus  of,  428 
Coefficient  of  partage,  25 
Coelom,  36,  37 
Coitus,  1372 
Cold,  actions  of,  on  muscle,  233 

sensations,  conduction  in  cord,  404 

spots,  543 
Collagen,  117 

action  of  gastric  juice  on,  772 

food-value  of,  722 
(Collateral  sympathetic  ganglia,  522 
Collaterals  in  cord,  396,  403 
Collecting  tubales  of  kidney,  1265 
Colloidal  metals,  155 

particles,  movements  of,  161,  162 
size  of,  156 

solution,  grades  of,  168 

solutions,  phases  in,  168 
Colloids,  22,  26,  79,  153-167 

adsorption  by,  157,  163 

aggregation  of,  163 

charge  of,  162,  164 

coagulation  of,  166,  167 

combination  between,  166 

dissociated,  153 

electrical  properties  of,  161-166 

heat  coagulation  of,  79,  167 

imbibition  by,  168 

of  serum,  166 

optical  properties  of,  160 

osmotic  pressure  of,  158 

precipitation  of,  163 

surface  phenomena  of,  157,  164 


Colon,  movements  of,  822-825 
Colostrum,  1385 
Colour-blindness,  646 
Colour,  contrast  phenomena,  649 

mixers,  644 

saturation,  642 

vision,  641-652 

Edridge-Green'  s  classification,  647 
Hering's  theory,  646 
Yoimg-Helmholfz'  theory,  645 
Combination  tones,  568 
Comma  tract,  399 
Commissural  cells  of  cord,  359 

fibres  of  cerebrum,  482 
Commissure  of  Giidden,  437 
Commutator,  see  Reverser 
Comparative  physiology,  2 
Compasses  test,  548 
Complemental  air,  1170  , 
Complementary  colours,  643 
Complement,  1159 
Compressor  urethrfe,  1292 
Concentration  cell,  190 
Conchiolin,  120 
Condenser,  214 

discharges,    use    of,    in    excitation, 
295 
Conduction,  irreciprocal,  310,  340 
Cone  cells,  623 

function  of,  641 
Congo  red,  adsorption  of,  164 

colloidal  properties  of,  152,  159 
Conjugate  deviation,  496,  655 

foci,  588 
Conjugated  proteins,  112 
Conjunctival  reflex,  664 
Connective  tissues,  action  of  gastric  juice 

on,  771 
Consciousness,  10 
Conservation  of  energy  in  body,  3,  695 

of  mass,  3 
Consonance,  566 
Consonants,  584 
Constant  current,  207 

flow  in  capillaries,  992 
Constrictor  fibres  to  limbs,  1120 
Contractile  stress,  224,  227 

tissues,  197,  278 

vacuole,  15,  36 
Contraction,  paradoxical,  318 

remainder,  234 

secondary,  262 

voluntary,  266 

wave  in  muscle,  225 
Contrast  in  sensation,  538 
Conus  arteriosus,  1006 
Convection,  loss  of  heat  by,  1313 
Convoluted  tubules,  1265 

secretion  by,  1279 
structure  of,  1266 
Co-ordinated  movements,  mechanism  of, 

382 
Copper,  48 

ferrocyanide  cell,  139 
Cord,  trophic  functions,  394 
Cornea,  603 
Corpora  mammillaria,  421,  422 


INDEX 


1401 


Corpora  quadrif^cniina,  40t»,  421 
Corpus  Arantii.  10()() 

callofsuin,  482 

(lentatum  of  cercbclliim,  420 

luteum,  formation  of,  1308 
function  of,  13fi3 
spurium,  1309 
subthalamicuni,  42r> 
striatum,  410.  47/3 
trapezoidcs,  418,428,436 
Corresponding  points,  656 
Cortex,  histological  localisation  in,  488 

reciprocal  innervation  from,  494 

thickness  of,  487 
Corti's  organ,  574 
Cortical  areas,  sensory,  501 
motor,  494 

epilepsy,  496 

excitation,    latent    period    of,    494, 
501 

inhibition,  494,  499 

motor     functions,      characters     of, 
507 
Costal  respiration,  1167 
Crampton's  muscle,  610 
Cranial  autonomic  fibres,  527 
Cranial  nerves,  functions  of,  463-469 

nuclei  of,  426,  463-469 
C'rayfish,  central  nervous  system,  330 
Creatine,  92,  238,  866 
Creatinine,  866,  867 

estimation  of,  1261 

in  urine,  1247 

tests  for,  1247 
Crescents  of  Gianuzzi,  743 
Cretinism,  1327 
Crico-arj'tenoid  joint,  579 
Cricoid  cartilage,  578 
Crico-thyroid  muscle,  580 
Crista  acustica,  676 
Crossed  pyramidal  tract,  398 

reflexes,  342 
Crura  cerebri,  421 

development  of,  409 
(Uusta,  421 
Crystallin,  108 
('rystalline  lens,  604 
Crystallisation  of  egg  an)uniin,  80 

of  scrum  alljiiniin,  80 
Crystalloids,  154 

diffusibility  of,  151 
Crystals,  mixed,  81 
Cuorinc.  62 

Curare,  action  of,  207,  291 
Current,  demarcation,  2()2 

minimal  gradient  of.  306 

of  action,  E.M.F.  of.  2()2 

of  injury,  189,  252,  262 

of  rest,  252 
Curvatures  in  eye,  .592,  603 
Cushnii  on  renal  resorption,  1283 
Cutaneoiis  end-organs,  554 
sensation,  542-554 
sensibility,  classification,  552 
Cutis  vera,  1299 
Cyanuric  aeid.  1246 
Cysteine,  90 


(Cystine,  95,  100,  1250 
Cytase,  77,  724 
Cytolysins,  1159 
Cj'toplasm,  15,  17,  18 
Cytosinc,  I  ]  5.  876 


D  :  N   RATIO     in     diabetes,    897,    9(J6, 

911 
Daniell  cell,  190,  207 
Dark-adapted  eye,  538,  040 
D' Arsonvdl  galvanometer,  255 
Decerebrate  dog,  445 

frog,  444 

pigeon,  445 

rigidity,  444,  448,  507 
Decidua,  formation  of,  1377 
Decussation  of  fillet,  415 

of  pyramids,  398,  412 
Deep  sensibility,  389,  552 
Defects  of  eye,  594 
Defaecation,  824 
Defence,     chemical,     against     infection, 

1152-1161 
Deamination,  84,  171,  860 

energy  changes  in.  862 

reversibility  of,  861 
Dead  space  (in  lungs),  1170 
Decapitate  animal,  372 
Decarboxylation.  172 
Deglutition,  758-764 

movements  of  larynx,  761 

muscles  of,  760 

nervous  mechanism  of,  763 

effect  of,  on  respiration,  760,  764 

sounds,  759 

study  of.  by  Rontgen  raj's,  759 

stages  of,  700 

time-relations,  762 
Dciters'  cells,  575 

nucleus,  429.  431,  454 
connections,  456 
Delirium  cordis,  1085 
Demarcation  current,  189,  253.  2()2 

compensation  of.  254 
E.M.F.  of,  254,  262 
Demilune  cells.  743 
Dendrites,  338 
Dental  consonants.  580 
Depressor  reflexes,  1097.  1127 
Dcscemefs  membrane.  (i04 
Descending  tracts.  438 
Detrusor  urina\  1290 
Dcutero-albumose.  770 
Deuterocerebrum,  331 
Development.  1356-1360 
Dextrins,  75 
Dextrose,  68 
Diabetes,  903-914 

in  fasting  animals.  906 

in  man,  912 

pancreatic.  910 

sTigar  consumption  in.  912 
Diabetic  puncture.  004 
Dialysis.  151 

in  sterile  solution.  152 
Diamino-acids,  92,  101,  107 


1402 


INDEX 


Diamino-acids,  precipitation  of,  101 
Diamino-caproic  acid,  173 
Diamino-nitrogen  of  proteins,  101 
Diamino-trioxydodecoic  acid,  93,  97 
a-5-diamino-valerianic  acid,  87.  90,  93 
Diaphragm,  movements  of,  1165 

muscles  of,  1164 
Diastase,  75 

Diastolic  arterial  pressure,  987 
Dichromatic  vision,  646 
Dietaries,  728 

Diet,  normal,  of  man,  726-736 
Diencephalon,  409,  441 
Difference  tones,  568 
Differential  blood-gas  apparatus,  1178 
Diffusion,  137,  145 
coefficient,  145 
of  solutes,  145 
Digestion,  737-853 

course  of,  847-850 
in  duodenum,  848 
in  intestme,  788-816 
in  stomach.  766-781 
gastric,  768 
pancreatic,  788 
salivary,  740-757 
Dihydroxybenzenes,  55 
Dilatator  pupillse,  612 
Dilemma,  518 
Dimethylaniine,  54 
Dioptre,  definition  of,  590 
Dipeptides,  99 
Diphasic  variation,  256 
Direct  cerebellar  tract,  401 

vision,  627 
Disaccharides,  67,  73 
Discus  proligerus,  1367 
Dissimilation,  4,  26,  28 
Dissociated  colloids,  153 
Dissonance,  565 
Distearyl-lecithin.  63 
Diuretics,  action  of,  1274 
Divers'  palsy,  1230 
Dominant  characters,  1359 
Dorsal  cerebellar  tract,  401 
Dromotropic  effect  of  vagus  excitation, 

1091 
Dry  cell,  208 

Du  Bois  Raymond's  key,  209 
Ductless  glands,  1317-1337 
Ductus  arteriosus,  1379 
Dudgeon's  sphygmograph,  1038 
Dulcite,  68 
Dyne,  definition,  295 
Dysoxidisable  substances,  1233 

Ear,  analysis  of  sounds  by,  568 

external,  569 

internal.  573 

physiology  of,  569-577 
Eck's  fistula,  858 
Edestin,  108 

composition  of,  100,  103 
Edkins  on  gastric  secretion,  779 
Edridge-Green,    classification    of    colour- 
vision,  647 
Efferent  nerves,  285 


Efferent  path.  369 

projection  fibres,  479 
tracts,  cerebellum,  454 
Efficiency  of  machines,  263 
Egg  albumin,  108 

composition  of,  100 
crystallisation  of,  80 
Ehrlich's  side- chain  theory,  1156 

methylene  blue  experiment,  1186 
Eighth  nerve,  nucleus  of,  428,  466 
Einthoven  galvanometer,  255 
Elasticitj'  of  muscle,  228 
Elastin,  119 

action  of  gastric  juice  on,  771 
Elastose,  111 
Electrical  capillarity,  193 

changes  in  living  tissues,  189-194 
in  muscle,  251 
properties  of  colloids,  161-166 
stimulation,  nature  of,  304 
variations,  effect  of  temperature  on, 

258 
variation,  time-relations  of,  257 
Electrocardiograms,  261,  1069 
Electrodes,  non-polarisable,  251 
Electrolytes,  conductivity  of,  142 
Electrolji:ic  dissociation,  189 

solution  tension,  190 
Electrotonic  current,  315 
Electrotonus,  297 

influence  of  intrapolar  length,  301 
Electro- vagogram,  1219 
Eleidin,  1299 

Embryo,  nutrition  of,  1378 
Emmetropic  eye,  595 
Emulsion,  61 

theor}'  of  protoplasm.  19 
Endocardiac  pressure,  1009-1017 

negative  phase,  1016 
Endolymph,  573 
End- plate  delay.  311 
End- plates,  204,  310 

effect  of  nicotine  on,  312 
fatigue  of,  292 
End-products,  effect  of,  on  ferments, 

185,  186 
Enemata,  nutrient,  value  of,  815 
Energy  balance-sheet  of  body,  693 
exchange,  3,  28 

exchanges  of,  in  body,  693-697 
loss  in  transformation,  264 
sources  of,  26 
total  daily  output  of,  728 
transformations  of,  136 
Engelmann''s  contractile  strings,  263 
Enterokinase,  789,  792 
Enteroceptive  nervous  system,  534 
Enterograph,  817 
Entoptic  phenomena,  596 
Enzymes,  see  Ferments 
Eosinophile  leucocytes,  918 
Ependyma,  408,  423 
Epiblast,  36 

Epicritic  sensibility,  552 
Epididymis,  function  of,  1365 

structure  of,  1364 
Epileptic  aurae,  497,  503 


INDEX 


1403 


Epithelium,  ciliated,  277 
f]quiiibration.  449 

dynamic,  U77 

functions  of  labyrinth  in.  OT" 

static,  680 
Erectile  tissue,  1365 
Erection,  l."}6o 
Erepsin,  810 
Erg,  definition,  295 
Ergastoplasm,  753 
Ergotoxin,  action  of,  1324 
ErlfiiKjefit  sphygmomanometer,  988 
Erythroblast.s.'940 
Erythrode.vtrin,  75,  741 
Ji.^li'ich's  reaction,  105 
Esters.  50,  51,  59 

mixed,  59 

glyceryl,  59 
Ester  method  for  separation  of  amino- 

acids,  89 
Ethereal  sulphates,  excretion  of,  869 
Ethylamine.  54 
Euglobulin,  977 
Eustachian  tube.  571 

valve,  1379 
Excitabilitj-,  28 
Excitation,  duration  of  current,  305 

effect  of  intrapolar  length,  301 

minimal  gradient,  306 

Nernsl's  theory,  321 

rate  of  change,  304 

strength  of  current,  305 

time,  300 

without  contraction,  258 
Excitatory  process,  nature  of,  319 

response,  nature  of,  305 
Exophthalmic  goitre,  1329 
Extensibility  of  muscle,  228 
Extensor  reflex.  376 
E.xternal  auditory  meatus,  569 
Exteroceptive  nervous  system,  534 
Eye,  angle  between  axes  in,  597 

centring  of,  596 

constants  of,  in  man.  592 

dark-adapted.  538 

filtration  angle  of.  667 

movements,  centres  for,  460,  496 

optical  defects  in,  594 
Eyeball,  dioptric  mechanism  of,  587,  590 

electrical  changes  in,  631 

nutrition  of,  664-668 

rotation  of,  655 
Eyeballs,  movements  of,  653-657 
Eye-muscles,  extrinsic,  653 
intrinsic,  615 

innervation  of,  615 

FAfiAi-  nerve,  nucleus  of,  427,  429,  467 
r"a(ilitati<)n  of  reflexes.  344 
Fseces,  composition  of.  851 

examination  of.   in   metabolism  cx- 
])i'rim<nts.  726 
False  vocal  fords.  579 
Fiir(itliii/-7\ifnilfill  ]>li<-ni)nu-non.  160 
Far  point  of  vision.  <>08 
Fasciculus  rctrnflcxus,  476 

solitarius.  414.  426 


Fasting,  metabolism  in,  692,  698-705 
Fatigue,  cause  of,  235 

muscular,  234 
Fat,  49,  58,  (iO,  885 
absorption  of.  832 
acid  number  of,  61 
composition  of,  885 
depots,  884 
estimation  in  food,  686 

in  faeces,  727 
formation  from  food,  886 

from  carbohydrates,  887 
from  proteins,  890 
functions  of.  885 
history  of,  in  body,  884-898 
in  intestinal  epithelium,  834 
iodine  number  of,  61,  885 
metabolism  in  starvation,  705 
oxidation  of,  894 
saponification  number  of.  61 
solubilitv  of,  836 
stains  for,  833 
sjTithesis  of,  1.32,  188 
utilLsation  of,  in  body,  892 
Fats,  action  of  gastric  juice  on,  773 

influence  of,  on  metabolism,  711 
Fatty  acids,  53,  59 

heat  equivalents,  862 
volatile,  61 
Fatty  degeneration,  nature  of,  833 
Fechner's  law,  539,  548 
Fehling's  test,  69,  12.34 
Fenestra  ovalis,  573 
Fenton/s  reaction.  1237 
Ferment  action,  adsorption  in.  187 

reversibilitvof,  185,  187 
velocity  of '181,  183 
Fermentation  in  stomach,  767 
Fermentation  test,  1255 
Ferments,  175-188 

action  on  optical  isomers,  186 

adenase,  878 

amylase,  176 

arginase,  176.  866 

as  catalvsers,  177 

catalase,  1237 

characters,  175 

classification.  176 

deaminising,  171.  176 

definition,  175 

effect  of  end-products  on,  185 

enterokinasc,  176 

erepsin.  176 

inverting,  176 

isolation  of.  175 

laccase,  1237 

lactase.  176 

lactic,  176 

lipase.  176.  188 

maltase.  176.  187 

nuclca.se.  877 

optimum  temperature  for.  178 

oxidases,  1237 

jK-psin.  176.  188.  768 

peroxitlase,  1237 

properties  of.  176 

rennin.  772 


1404 


INDEX 


Ferments,  specificity  of,  178,  186 
as  synthetic  agents,  187 
svicrase,  17(i 
trypsin,  176 
iirease,  176 
uricolytic,  879 
zymase,  176 
Fertilisation,  1352-1355,  1372 

artificial,  1355 
Fick  and  Wislicenus's  experiment.  714 
Field  of  vision,  628 
Fifth  nerve,  nucleus  of,  427 
Fibre  layers  in  cortex,  486 
Fibrillffi  of  muscle,  199 
Fibrin,  976 

composition  of,  103 
ferment,  950 

fate  of,  956 
peptone.  111 
Fibrinogen,  108,  949,  975 
Fibroin,  119 

Fick  and  Wisliceyms's  experiment,  714 
Fillet,  415,  434,  478 
decussation  of,  415 
lateral,  419,  436 
Final  common  path,  387 
First  focal  plane,  591 
point,  591 
Fischer's  method  for  separating  amino- 

acids,  89 
Flack-Keith  node,  1072 
Flechsig's  myelination  method,  360 
Flexion  reflex,  376,  384 
Flicker  phenomena,  638 
Fluoride  plasma,  clotting  of,  958 
Fluorine,  48 
Foci  in  eye,  592 

of  lenses,  588 
Foetal  circulation,  1379 
FolirCa  method  for  ammonia  estimation, 
1260 
for  urea  estimation,  1260 
for  uric  acid  estimation, 
1261 
Fontana,  spaces  of,  604 
Food,  amount  necessary,  727 

analysis  of,   in   metabolism   experi- 
ments, 686 
materials,  utilisation  of,  7 
Food-stuffs,  digestibility  of,  727 

changes  in  alimentary  canal, 

737-739 
heat -values  of,  694 
history  of,  854-914 
proportions  necessary,  730 
significance  of,  718-725 
Foramen  of  Monro,  424 
Foramen  ovale,  572,  1379 

rotundum,  574 
Fore-brain.  408,  422 
Formic  acid,  53,  59 
Fornix,  473 

pillars  of,  424 
Fourth  nerve,  nucleus  of,  426,  430,  464 
Fovea  centralis,  625 
Frank's  manometer,  1011 
valve,  1012 


Frank  on  pulse,  1043 
Fraiinhofer's  \incs,  635 
V.  Frey,  testing  hairs,  546 
Frontal  lobe,  473 
Frog,  muscles  of,  204 
Frog's  heart,  anatomy  of,  1057 
Fronto -pontine  fibres,  480 
Fructose,  66,  69 
Fundamental  tone,  564 
Fungiform  papilla,  556 

Galactolipines.  62 
Galactosamine,  116 
Galactose.  66.  70 
Gall-bladder,  803 

innervation  of,  805 
Galvanic  cells,  bichromate,  208 

concentration,  190,  191 
Daniell.  190,  207 
dry,  208 
E.M.F.  of,  192 
Leclanchc,  208 
positive  element,  207 
positive  pole,  208 
source  of  energy,  191 
Galvanic  excitation,  law  of,  296 
Galvanometer,  D'Arsonml,  255 

Einthoven's,  255 
Ganglia,  evolution  of,  329 

sympathetic,  522 
Ganglion  habenulse.  423 

Gasserian  428,  430 
Gaseous  diffusion,  149 

exchange  in  lungs,  1190-1199 

secretory  theory,  1197 
metabolism  of  salivary  glands,  755 
Gases,  tension  of,  in  liquids,  1180 
Gas  laws,  137 
Gastric  digestion,  768 
fistula,  766,  773,  774 
hormone,  779 
juice,  766 

acid  of,  767 

acidity  of,  768 

action  of,  on  carbohydrates,  772 

action  of,  on  fats,  773 

action  of.  on  proteins,  768 

action  on  food-stuffs,  768 

'  appetite  '  secretion,  775,  780 

composition  of,  767 

chemical  excitants,  778 

determination    of    hydrochloric 

acid  in,  768 
inverting  power  of,  768 
rate  of  secretion  of,  775 
variations  in,  481,  774-777 
psychical  secretion  of,  775 
secretion  of,  773 
secretin,  779 
Gastrocnemius  of  frog,  204 
Gelatin,  118 

composition  of,  100,  103 
food  value  of,  723 
Gels,  155 
Gemmules,  21 
General  physiology,  13-194 
Genicidate  bodies,  422,  424,  425,  431,  437 


INDEX 


1405 


Genital  hormones,  1362 
Geotaxis,  29 
Germ  eells,  1345 

chromosomes  in,  1352 
division  of,  1348 
Germinal  spot,  13<)8 

vesicle,  13GS 
Gierke,  respiratory  Ijundie  of,  1201 
Glaucoma,  668 

Gliadui,  composition  of,  100,  103 
Gliadins,  109 
Globulin,  adsorption  by,  165 

salts  of,  977 
Globin,  932 

composition  of,  100 
Globulins,  108 

Glossopharyngeal  nerve,  nucleus  of,  468 
Glottis,  579,  583 
Glomerulus,  filtration  in,  1270 

of  kicbiey,  1265 

pressure  of  blood  in,  1271 
Gluconic  acid,  68 
Glucosamine,  70,  96,  116 
Glueosazone  crystals,  1254 
Glucose,  66,  69 

in  blood,  899 

identification  of,  69,  1255 

lactonic  structure,  71,  72 
Glucosides,  71 
Glueosazone,  69 
Gluten  peptone.  111 
Glutamic  acid,  89,  91,  101 
Glutelins,  109 
Glycerol,  51,  58,  62 
Glycogen,  76,  239,  899 

preparat'on  of,  900 

formation  of,  900-902 
Glycoproteins,  116 
Glyceric  aldehyde,  135 
Glycerides,  59 
Glyeerophosi^horic  acid,  63 
Glyceryl  esters,  59 
Glycine,  86,  89,  100 

ring  formida  of,  87 

salts  of,  87 

ester,  polymerisation  of,  08 
Glycosuria,  903-914,  1253 

alimentary,  904 
Glycuronic  acid,  71,  1255 
Glycyl-glycine,  98 
Glyoxylic  acid,  104 
Goitre,  1326 

GolW  column,  367,  397,  399 
Gonads,  1346 

QolcKs  heart  apparatus,  1081 
Gowefs  tract,  401,  417,  437 
Golji  cells,  359,  452 

corpuscles,  554 

network,  339,  348 
CJraafian  follicles,  structm'c  of,  13()7 
Gracilis  exi)eriment,  285 

of  frog,  205 
Gmluiin  on  colloids,  154 
Grape-sugar,  .scr  Glucose 
Graphic  metliod,  217 
Gravity.  elTeit  of,  on  ciiiuiation,  1052 
Green-blindness,  649 


Grey  matter  of  cortex,  minute  structure 
of,  483 

rami,  522 
Growth,  4 

of  cells,  1341 

food  requirements  in,  734 
Guanine,  114,  116,  878 
Guanylic  acid,  116 
Gudden's  commissure,  437 
Gunzberg's  reagent,  767 
Gustatory  area,  506 

sensations,  557 
Guttural  consonants,  580 
Gymnema  sylvestre,  eifect  on  taste,  557 

Hair  follicles,  1300 
Hairs,  sensibility  of,  547 
Haldane-Pembrey  respii'ation  apparatus, 

689 
Hales'  experiment,  983 
Haploscope,  656 
Haptogen,  1386 
Haptophore  group,  1157 
Harmonic  intervals,  566 
Harmonics,  564 
Hausmami' s  method  for  distribution  of 

nitrogen,  101  tT''^ 

Uayem's  fluid,  944  '' 

Hajmatin,  107,  112,  932 

chemical  relationships,  936 

synthesis  of,  937 
Hsematinic  acids,  936 
Ha^matoporphyrin,  933,  935 

combination  with  iron,  938 

in  urine,  1252 
Hajmin,  932 

structure  of,  937 
Haemochromogen,  933,  937 
Haemocyanin,  48,  103 
Hsemocytometer,  968 
Hajmodjomograph,  1001 
Hajmoglobin,  46 

absorption  spectrum,  930 

composition  of,  103,  112 

crystallisation  of,  80 

derivatives  of,  932 

dissociation  curve,  1182,  1183 

iron  in,  81 

molecular  weight  of,  160 

oxygen  capacity  of,  929,  1181 

preparation  of,  927 

reduction  of,  929 

union  with  oxygen,  1181 
Hajmoglobin-crystals,  928 
Hiemoglobinometer,  966,  968 
Haemolysins,  1159 

Hemolysis,  25,  141,  926,  943,  1131,  1159 
Haemolytic  sera,  1159 
Hsemopyrrol,  936 
Haemorrhage,  1131 
Head  on  cutaiveous  sensibility,  552 
Head' a  diai)inagni  slip.  1215 
Hearing.  trUjihone  theory.  577 

HvliiihoUz's  theory,  576 

physiology  of,  569 

Rulhcrjord's  theory,  577 
ira//e;'6'  theory,  577 


1406 


INDEX 


Hearing,  end-organ  of,  573 
Heart,  action  of  sympathetic  nerves  on, 
1094 
action  of  vagus,  1089 
changes  in  form,  1017 
diastolic  filling.  1024 
effect  of  calcium  on,  1080,  1093 

potassium  on,  1080,  1093 
muEOirine  on,  1009 
nicotine  on,  1062,  1092 
electrical  variations,  259 
frog's,  automatic  contraction,  1058 
human,  electrocardiogram  of,  1069 
influence  of  temperature  on  rate  of, 

1079 
inhibition  of,  1090 
intracoronary  pressure,  1085 
mammalian,  ganglion-cells  in,  1068 
mechanism  of,  1004-1033 
nerve  fibres  in,  1064 
nutrition  of,  1084 
primitive  vertebrate,  1070 
rate  in  exercise,  1100 
reflexes,  1095 
rhythm,  reversal  of,  1071 
sounds,  1020 

graphic  record  of,  1022 
systolic  output,  1026-1031 
theories  of  inhibition  of,  1093 
work  of,  1031-1033 
Heart-beat,  causation  of,  1057-1086 
contraction  wave,  1066-1068 
electrometer  records  of,  1066 
in  mammals,  1068-1073 
myogenic  hypothesis,  1059 
neurogenic  hypothesis,  1058 
propagation  of  contraction  in,  1062 
significance    of    carbon    dioxide  for, 
1083 
Heart -block,  1072 
Heart-fibrillation,  1085 
Heart-lung   preparation.   Starling's    me- 
thod, 1027,  1028 
Heart -muscle,    '  all     or     none  '     pheno- 
menon, 1074 
excitation  of,  1074 
influence  of  tension  on,  1077 

of    chemical   substances    on, 
1079 
physiological  properties  of,  1074- 

1077 
refractory  period  of,  1075 
summation  of  stimuli  in,  1075 
Heart-musculature,  1005 
Heat-coagulation,  167 
Heat-engines,  efficiency  of,  263 
Heat-loss,  regulation  of,  1313 
production  in  body,  1310 
in  muscle,  246 
regulation,   nervous   mechanism   of, 
1316 
in  new-bom,  1316 
rigor,  233,  239 

sensations,  conduction  in  cord,  404 
sexual,  in  animals,  1371 
spots,  543 
values  of  food-stuffs,  694 


Heats  of  combusition,  174 
Heller's  test,  106,  1253 
Helmholtz  resonators,  565 

side  wire,  211 
Helwec/s  bundle,  399 
Hemiansesthesia,  503 
Hemianopia,  460,  505 
Hemiplegia,  503 
Henle's  loop,  1265 
Hensen's  disc,  203 
Heredity,  1356-1360 

basis  of,  21 
Hering's  theory  of  colour-vision,  646 
Herpes  zoster,  causation  of,  1124 
Heteroalbumose,  111 
Heterocyclic  amino-acids,  94 
Heterotype  mitosis,  1350 
Hexachromic  vision,  648 
Hexone  bases,  92 
Hexoses,  67 

classification  of,  67 

derivatives  of,  70 

reactions  of,  68 
Hmd-brain,  408,  412-420 
Hippocampal  commissure,  482 
Hippocampus,  473 
Hippuric  acid.  870,  1250 
Hirudinised  blood,  948,  958 
His'  bundle,  1006,  1072 
Histidine,  95,  101,  115 

fate  of,  873 
Histological  differentiation,  7,  33" 

localisation  in  cortex,  488 
Histones,  102,  107,  112 
Hoffmann's  test,  94 
Hopkins'  test  for  lactic  acid,  241 

for  tryptophane,  104 
Hopkins-Adamkiewicz  reaction,  104 
Homogentisic  acid,  55,  870,  1256 
Homoiothermic  animals,  1308 
Hormones,  genital,  1362 

mammary,  1362 

nature  of,  1319 

pancreatic,  797 
Horopter,  656 

HUfner's  method  for  urea  estimation,  1259 
Human  stomac  ,  form  and  movements, 

783 
Hiirthle's  manometer,  1010 
Hyaline  corpiiscles,  918 
Hyaloid  membrane,  004 
Hyaloplasm,  19 
Hydrajmic  plethora,  1129 

effect  on  volume  of 
urine,  1275 
Hydrated  proteins,  109 
Hydrazones,  68 
Hydrocarbons,  49 

unsaturated,  50 
Hydrocele  fluid,  959 
Hydrochloric  acid  in  gastric  juice,  767, 

768 
Hydrogels,  79,  155 
Hydrogen,  42 

Hydrogen  ion  concentration,  determina- 
tion of,  1190 
Hydrolysis,  171 


INDEX 


1407 


Hydrolysis  of  casein,  89 

of  proteins,  83,  80,  l<»9 
Hydroquinone,  55 
Hydrosols,  154 

osmotic  pressure  of.  158 

properties  of,  157,  160 
Hyperglycsemia,  911 
Hypermetropia,  595 
Hvperpnoea,  1204 
Hypoblast,  .Hi 
Hypogastric  nerves,  action  on  bladder, 

1296 
Hypfjgastric  reflex,  530 
Hyixjglossal  nucleus,  42G,  409 
Hypoxanthine,  114,  878 

Idextical  points  in  retina,  C5G 
Idiopathic  epilepsj-,  497 
Ileocolic  sphincter,  822 
Illusions  of  size,  661 
Image,  size  of,  589 
Imbibition  bj-  colloids,  168 

relation  to  constitution,  169 

tenacity  of,  168 

pressure,  168 
Iminazoi,  115 

ring,  95 

synthesis  of,  130 
Iminazol-alanine,  95 
Immunity,  1152-1161 
Impregnation,    nervous    mechanism    of, 

1373 
IncLsura  angularis,  783 
Incus,  571 

Indican,  of  urine,  1251 
Indigo  as  catalyser,  179 
Indigo  -  carmine,    excretion    by    kidnev, 

1281 
Indirect  vision,  627 
Indol,  fate  of,  870 
Induced  currents,  210,  211 
Inductorium,  210,  211 
Infection,  cellular  defence  against,  1 1 43- 
1151 

chemical     defence    against,     1152- 
1161 
Inferior  cervical  ganglion,  520 

mesenteric  ganglion,  522 

oblique  muscle,  653 

pedtincles  of  cerebellum,   414,   415, 
417 
Inflammation.  921,  1146 
Infundibula,  1163 
Infundibulum  in  brain.  422 
Inhibition,  28,  344,  383 

Gaskell's  theory  of,  1093 

of  heart,  nature  of,  1093 

in  peripheral  ganglia,  531 
Injurj'.  effect  of.  on  nerve,  309 
Injurj'-current,  189.  252 
Inner  cell-laniina  of  cortex,  484 

fibre-lamina  of  cortex,  483 

line  of  Btiillarger,  486 
Inogen,  244 

Inorganic  food-stuffs.  724 
Inosinic  acid,  874,  876 
Inosit.  239 


Inotropic     effect     of    vagus    excitation, 

1091  ^     fjn 

Instrumental  inertia,  220,  1044  jr     j^ 
Insular  lobe,  473  m  -^ 

Intercostal  muscles,  action  of,  1107 
Internal  capsule,  412,  424,  475,  479JJ 

ear,  573 

respiration,  1162 

restiform  body,  410      ' 

secretions,  1317-1337  I 
Intestine,  absorption  in,  820 

law  of,  819 

movements  of,  8 17-825 J 

pendular  movements  of,  817,  818 
Intestinal  fistula,  808 

juice,  807 

characters  of,  810 
secretion  of,  809 
Intima  of  artery,  981 
Intra-auricular  presstire,  1014 
Intra-molecular  oxygen,  27,  244 
Intra-ocular  fluid,  666 

pressure,  605,  665 

pressure  and  blood-pressure,  667 
Intra -thoracic  pressure,  1169 
Intra-ventricidar  pressure  curve,  1013 
Intra -vesical  pressure,  1293 
Intra-vitam  staining,  25 
IniUin,  76 
Inversion,  74,  178 
Invertase,  74 

of  intestinal  juice,  811 
Invert  sugar,  74 
Iodine,  48 

in  thjToid  gland,  1329 

number  of  fats,  61 
lodothyrin,  1329 
lonisation,  142 
Ions,  189 

velocity  of  transport,  192 
Iris,  604 

functions  of,  612 

as  diaphragm,  597 

local  stimidation  of,  618 

nerve-supplv,  616,  618 
Irradiation,  383* 
Irreciprocal  conduction,  310,  340 
Iron,  46,  81 

excretion  of,  47 

in  large  intestine,  815 

in  hsemoglobin.  81 

in  liver.  943 
Island  of  Heil,  475.  478 
Islets  of  Langerhans,  origin  of,  801 

Benslfiy'a    views, 
802 
Isoamylamine,  173 
Isodynamic  food-stuffs,  707 
Isoleucine,  91 
Isomaltose,  185,  187 
Isometric  contraction,  beat  of,  250 

of  heart.  1078 

lever,  220.  221 
Isosmotic  solutions,  146 
Isotonic  lever.  221 

solutions.  925 
Isotropous  substance,  203 


1408 


INDEX 


Jacksonian  epilepsy,  493,  497 
Jaffe's  test,  1247 
Joints,  sensibility  of,  671 
Jugular  ganglion,  528 

Karyokinesis,  6'te  Mitosis 
Karyosome,  17,  34 
Keith-Flack  node,  1072 
Keratin,  composition  of,  100,  119 
Keratins,  95,  119 
'  Kernleiter  '  model,  316,  319 
Keto-acids,  53 

origin  of,  861 
a-ketonic  acids,  172 
Ketoses,  65 
Key,  kick- over,  218 
Keys,  208 
Kidney,  adaptability  of,  1286 

cells,  structure  of,  1281 

functions  of  glomeruli,  1269-1277 

nerves  of,  1267 

secretion  in  frog,  1280 

of  water  and  salts,  1269-1277 

structure  of,  1264-1267 

tubules,  functions  of,  1279 
absorption  in,  1283 

work  of,  1269 
Kinjesthetic  areas,  500 
Knee-clonus,  379 
Knee-jerk,  377 

abolition  of,  378 

exaggerated,  509 

latent  period,  378 
Knoop  on  deamination,  861 
Knowlton  and  Starling  on  glucose  con- 
sumption of  heart,  903,  912 
Krause's  membrane,  199 
Krogh's  microtonometer,  1193 
Kiihne's  gracilis  experiment,  285 
Kymograph,  984 

Labial  consonants,  586 

Labour,  1382 

Labyrinth,  evolution  of,  674 

functions  of,  449 
Labyrinthine  sensation,  674 
Laccase,  1237 
Lacrymal  gland,  664 
Lactalbumen,  1387 
Lactase,  action  of,  176,  183,  184 

in  intestinal  juice,  811 
Lactation,  1384-1393 
Lacteals,  828,  1134 
Lactic  acid,  53 

Hopkins'  test,  241 

in  blood,  1210 

in  gastric  juice,  707 

in  muscle,  241 

in  urine,  242,  1210 
Lactoglobulin,  1387 
Lactosazone  crystals,  1254 
Lactose,  73,  74,  1387 
Lsevorotation,  57 
Lsevulinic  acid,  116 
Lagena,  675 
Lamina  cinerea,  422 
Langerhans'  islets  in  pancreas,  801 


Lanoline,  62 
Lardacein,  117 

Large  intestine,  absorption  in,  815 
excretion  in,  815 
functions  of,  813 
movements  of,  822-825 
Laryngoscope,  581 
Larynx,  anatomy  of,  578 

movements  of,  in  deglutition,  761 
Latent  period,  222,  227 
Lateral  columns  of  cord,  401 

crico-arytenoid  muscle,  581 

fillet,  419,  436 

sympathetic  ganglia,  522 

nucleus  in  medulla,  413 
in  pons,  417 
Lateritious  deposit,  1249 
Laurie  acid,  59 
Law  of  forward  direction,  330,  350 

of  the  intestines,  819 

of  specific  irritability,  536 
Lecithin,  47,  62 
Leclanche  cell,  208 
Lemniscus,  415,  434 
Lens,  604 

elasticity  of,  608 

variation  with  age,  608 
Lenses,  formation  of  images  by,  588 
Lenticular  ganghon,  615 
Legumin,  109 
Leguminous  nodules,  45 
Leucine,  90,  100,  101 

cones,  91 
Leucines,  oxidisability  of,  1234 
Leucocytes,  chemiotaxis  in,  1149 

classification  of,  918 

origin  of,  920 
Leucoplasts,  17 
Leucosin,  108 
Lever,  momentum  of,  220 
Levulose,  69 

Liehermanib'' s  reaction,  104 
Life,  evolution  of,  5,  6,  36 

laws  of,  8 

without  oxygen,  27 
Ligamentum  pcctinatum  iiidis,  004 
Light,  nature  of,  634 

reflex,  613  , 

Lignin,  118 
Lignoceric  acid,  59 
Limbic  lobe,  473 

Liminal  intensity  of  stimulus,  528 
Limulus  heart,  1064 
Line  of  Oennari,  486 
Lines  of  direction,  590 
Linin,  17 
Linoleic  acid,  60 
Linolinic  acid,  60 

series,  60 
Lipase  of  pancreatic  juice,  794 

in  gastric  juice,  773 

reversibility  of  action  of,  188 
Lipines,  62 
Lipoids,  24,  62 
Liquor  folliculi.  1367 
Lissauer's  tract,  366,  398,  403 
Liver,  bile  formation  in,  803 


INDEX 


1409 


Liver,  glycogen  of,  fl09 

hsemolyni^  in,  f(4.'} 

lymph  production  in,  1136 

formation  of  urea  in,  858 

of  uric  acid  in,  878 
Living  matter,  chemical  changes  in,  170- 

188 
Load,  effect  of  a  contraction,  231 
Local  reflexes,  529 

sign  of  tactile  sensation,  549 
Locke's  fluid,  1080 
•  Localisation  of  function  in  brain,  492 
Locomotion,  co-ordination  of,  391 
Locomotor  ataxia,  391 
Locus  perforatus  posticus,  422 
Long  ciliary  nerves,  615 

sight,  595 
Longitudinal  inferior  fasciculus,  481 

superior  fasciculus,  481 
Loudness  of  sound, 563 
Ludwir/s  Sfromuhr,  1001 

manometer,  983 
Luminosity  of  spectral  colours,  636,  642 
Lungs,  distensibility  of,  1168 

exchange  of  gases  in,  1190-1199 

vaso- motor  fibres  of,  1053 
Lutein,  1368 
Lui/s  nucleus,  425 
Lymph,  absorption  of,  1141 

movements  of,  1140 

production,  1135 

effect  of  capillary  pressure  on, 

1136 
in  small  intestine,  828 
osmotic  phenomena  in,  1137 

properties  of,  1134 

n'lle  of,  in  nutrition,  1142 

and  tissue  fluids,  1133-1142 
Lymphagogues,  1138 
Lymphatic  glands,  1134 

tissue,  structure  of,  920 
Lymphatics,  course  of,  1133 
Lymphocvte,  918 
Lysine,  92,  100 

decarboxylation  of,  173 
Lysins,  1154 

Macro-nitcletjs  of  paramoecium,  1343 
Macula  acustica,  449,  676 

lutea,  625 
Macdonald's  theory,  323 
MucdougalVs  theory,   muscular  contrac- 
tion, 264 
Macrophages,  1150 
Magnesium,  47 

excretion  in  large  intestine,  815 
Major  chord,  567 
Make  contraction.  215 

excitation,  296 

induction  shock,  211 
Mall  on  heart  musculature,  1005 
Malleus,  571 
Malpighian  follicles  of  spleen.  1335 

pyi'amids,  1264 
Maltase,  186 

of  intestinal  juice,  811 

reversibility  of  action.  187 


Malto-dextrin,  76 

Maltose,  73,  74,  75 

Mammary  gland,  structure  of,  1391 

hormones,  1363 
Mannite,  68 
Mannoso,  66,  70 
Manometer,  Hiirthles,  1010 

Ludivufs,  983 

maximum  and  minimum,  1012 
Marchi's  method,  361 
Marty's  law  of  blood  pressure,  1098 

sphygmograph,  1038 
Marginal  lobe,  473 
Mark-time  reflex,  388 
Marie's  tract,  399 
Marrow,  58 
Martinoitl  cells,  484 
Material  basis  of  body,  39,  135 
Matter,  exchanges  of,  in  body,  685-736 
Maximal  stimulus,  216,  230 
Mayer  cnxyas,  1110 
Mean  systolic  pressure,  995 
Mechanical  changes  in  muscular  contrac- 
tion, 217-229 

coagulation  of  colloids,  167 

efficiency  of  muscle,  250 

response  of  muscle,  230-236 
Mechanism,  9 
Meconium,  1379 
Media  of  artery,  981 
Medulla  oblongata,  412-417 

functions  of,  441 
Medullary  sheath,  280 
Medusa,  nervous  S3^stem  of,  326 
Meibomian  glands,  665 
Meiosis,  1350 
Meissnefs  corpuscles,  554 

plexus,  523,  529,  810 
Membrana  granulosa,  1367 

reticularis,  575 

tectoria,  575 

tympani,  569 
Membranes,     electrical     phenomena     at 
surface  of,  193 

permeabiUty  of,  24,  145 

semi-permeable,  147 
Membranous  labyi'inth,  573,  674 
Mendel's  law,  1359 
Menstruation.  1369 

relation  of  ovulation  to,  1370 
Mercurial  manometer,  983 
Mesencephalon.  409,  441,  443 
Mesial  fillet,  415,  434 
Mesotartaric  acid,  57 
Metabolism,   effect    of    foods    on,    706- 
712 

during  starvation,  698-705 

experiments,  analysis  of  excreta,  687 

general,  685-725 

influence  of  ago  on.  735 

of  carboiiydratos  on,  711 

of  fats  on.  711 

of  muscular  work  on.  713 

of  protein  on.  706 

of  temperature  on.  1306.  1311 

methods,  686-693 

of  muscle,  241 

89 


1410 


INDEX 


Metabolism,  of  nucleo-proteins,  874-883 

of  proteins,  854-S73 

relation  to  body  weight,  701 

to  surface  of  body,  702 
Metakinesis,  10 
Metal  '  sols,'  156,  178 
Metaplasm,  17 
Metaplasmic  products,  19 
Metaphase  of  mitosis,  1348 
Meta  position,  54 
Metaproteins,  109 
Metencephalon,  408,  441,  443 
Methsemoglobin,  931 
Methyl-acetate,  catalysis  of,  185 
Methylamine,  54 
Methyl  glucosides,  72 

glycine,  93 

guanidin  acetic  acid,  93 

purines,  115,  875 
MicelliB,  21 

Micro-nucleus  of  paramcecium,  1343 
Microphages,  1150 
Microsome,  17 
Microtonometer,  1193 
Micturition,  1289-1298 

nerves  of,  1295 

reflex, 1297 
Mid- brain,  421 

crusta,  421 
functions  of,  443 
pes,  421 

tegmentum,  422 
Middle  cell-lamina  of  cortex,  483 
Milk,  coagulation  by  pancreatic  j  nice,  793 

fats  of.  132,  1386 
origin  of,  1393 

human,  composition  of,  736 

properties  of,  1386 

proteins  of,  1386 

in  relation  to  growth,  735 

quantity  secreted,  1385 

salts  of,  1388 

secretion  of,  1384-1393 
Milk-sugar,  1387 
Millon's  reaction,  94,  104,  110 
Mineral  salts,  importance  of,  725 
Minimal  difference  method,  540 

effective  stimuli,  539 

gradient,  306 

stimulus,  216,  230,  538 
Mitosis,  1348 

heterotype,  1350 
Mitral  cells,'  476 

valve,  1006 
Modality  of  sensation,  535 
Molecular  layer  of  cortex,  483 
Molecules,  energy  in  solution,  136 

size  of,  155,  159 
MoliscK's  test,  69,  104 
Molybdic  acid  as  catalyser,  180,  182 
Monakotv's  bundle,  399,  438 
Mono-amino-dibasic  acids,  91 
Mono-aminx)-monobasic  acids,  89 
Mono-amino-nitrogen  in  proteins,  101 
Monochromatic  patches,  642 

vision,  646 
Monomolecular  reaction,  181 


Monophasic  variation,  257 
Monosaccharides,  67 
Moore's  test,  69 
Morphotic  proteins,  718 
Moss  fibres,  452 
Motor  aphasia,  512 

area,  lamination,  487 

cells  of  cord,  359 

centres,  ablation  of,  498 

end -plates,  204 

sensibility,  503 
'  Motor  points,'  302 

somatic  nuclei,  426 
Mountain  sickness,  1227 
Movement,  co-ordinated,  382 

and  sensation,  197-681 

sensations  of,  669-673 
Movements  of  alimentary  canal,  758,  782, 
817 

of  deglutition,  758 

of  large  intestine,  822 

of  small  intestine,  817 

of  stomach,  782 
Mucin,  action  of  gastric  juice  on,  771 
Mucins,  116 
Mucoids,  117 
Mucous  glands,  743 
Miiller's  law  of  specific  irritability,  286, 

536 
Multirotation,  71 
Murexide  test,  1249 
Muscae  volitantes,  596 
Muscarine,  action  on  heart,  1092 
Muscle,  afferent  nerves,  380 

anisotropic  substance,  203 

action  of  veratrin,  236 

arrested  contraction,  224 

break  contraction,  215 

chemical  changes  in,  237-245 

chemical  stimulation  of,  207 

clotting  of,  238 

composition,  237 

contractile  stress,  224 

contraction-remainder,  234 

demarcation  current,  189,  253,  262 

efficiency  of,  250,  715 

elasticity  of,  228 

electrical   variation,   effect   of   tem- 
perature, 257 

excitation  of,  206-216 

excitation  without  contraction,  258 

extensibility  of,  228 

heat- production  in,  246-250 

independent  excitability,  206 

injury-current,  189,  252,  262 

involuntary,  200,  271 

of  invertebrates,  277 

isotropous  substance,  203 

longitudinal  striation,  201 

make  contraction,  215 

mechanical  response  of,  230-236 

metabolism  of,  241 

production  of  carbon-dioxide,  242 

products  of  activity,  240-245 

reciprocal  innervation  of,  379 

red,  201 

reflex  tone,  448 


INDEX 


lili 


Muscle,  respiratory  quotient,  244 
source  of  energy,  24.3 
stimulation  by  constant  current,  207 

215 
thickening  of,  222 
utilisation  of  energy,  249 
voluntary  of,  197 

.structure,  199 
white,  202 
Muscle-current,  189,  252,  2.50,  258 
Muscle-curve,  correction  of,  220,  233 
Muscle  fibre,  199 

reversal  of  stripes,  203 
Muscle-fibrillae,  199 
Muscle-plasma,  237 
Muscle-sound,  2(J7 
Muscle-spindle,  U72 
Muscle-twitch.  214,  217,  222 
Muscle- wave,  225 

Musical  notes,  vibration  frequencies,  568 
Muscular  aSerents,  072 

contraction,  '  all  or    none  '    pheno- 
menon, 230 
Eiujelnuinns  theory,  263 
effect  of  drugs,  236 
of  fatigue,  234 
of  load,  231 
of  salts,  235 
of  temperature,  233 
of  tension,  2.50 
heat  production  in.  248 
latent  period  of,  222 
MacdougalVf  theory,  264 
mechanical  changes  in,  217-229 
nature  of.  263-205 
optical  method,  221 
osmotic  theory,  264 
point  of  stimulation,  218 
Schdfer's  theory,  203 
strength  of  stimulus,  230 
time-relations  of,  222 
voluntary,  266 

electrical  changes  in,  269 
record  of,  208 
contractions,  summation  of,  226 
energy,  source  of,  713 
exercise,  effect  on  circulation,  1099- 

1102 
movements,  co-ordination  of,  389 
relaxation,  222 
sense,  071 

psychology  of,  673 
sensibility,  paths,  503 
tone,  377,  .507 

relation  to  labyrinthine  sensa- 
tions, 678 
work,  energy  exchanges  in,  715 
effect  (in  metabolism,  713 
Muscularis  mucosa?  of  small  intestine,  828 
Musculi  papillares,  1006 
Musculus  vocalis.  581 
Myelencephalon.  408,  441 
Myelocytes,  920 
Myelination,  282 
method.  360 
My.-lin  sheath.  280-282 
Mylohyoid  of  frog,  20q 


Mvogen.  238 

fibrin,  238 
Myogenic  movements  of  intestine,  8l8 
Myohiomatin,  238 
My<jpia,  595 
Myosin,  108,  238 
Myosin  fibrin,  238 
Myosinogen,  237 
Myristic  acid.  .59 
Myxcedema,  1327 

Nasal  consonants,  586 
Near  point,  599,  608 
Xectocysts,  35 
Negative  after-image,  639 

polarisation  of  nerve,  317 
variation.  2.53 
ventilati«jn,  1217 
Negativity.  257 
Neopallium.  471 

evolution  of,  474 
Nerve,  core  model,  316 

double  conduction,  284 
electrotonic  current,  315 
electrotonus,  297 
endoneurium.  281 
excitability,    '  characteristic  '    of, 
295,  305 
effect  of  temperature  on,  308 
fatigue  in,  290,  320 
galvanic  excitation,  295 
human,  stimulation,  302 
law  of  forward  direction  in,  330,  3.50 
negative  polarisation,  317 
neurilemma,  281 
nodes  of  Ranriir,  281 
non-medullated,  281 
polarisation  in,  315 
positive  polarisation,  317 
primitive  sheath,  281 
unipolar  excitation,  302 
Nerve-axon,  280 
Nerve-block,  299 
Nerve-cell,  automaticity  of,  353 
functions  of,  351 
Oolgi  net,  339,  348 
NissVs  granules,  337 
pericellular  network,  348 
structure  of,  337 
Nerve-centres  in  medulla.  443 
Nerve-current,  Macdonald's  theory,  192 
Nerve-fibres,  279-323 

excitation  of,  294 
size  of,  281 
structure,  279 
Nerve- impulse,  283 

electrical  changes  accompanying, 

287 
influence  of  ilrugs  on,  292 
velocity  of.  283 
effect  of  temiH»rature  nn,  289 
cimditions  affet^ing.  280 
Nerve-injury,  effect  of,  309 
Nerve-trunk,  comp<isition  of,  369 
Nerves,  cranial.  463 

nuclei  of.  426,  463-469 
grafting  of,  285 


1412 


INDEX 


Nervi  erigentes,  functions  of,  528,  1121, 

1292,  1295,  1374 
Nervous  system,   evolution  of,  324-333 
ganglia,  329 
of  medusa,  326 
of  vertebrates,  334 
Neural  canal,  334 
Neurilemma,  281 
Neurine,  63 
Neuroblasts,  335 
Neuro-fibrillar  network,  484 
Neuro-fibrils,  333 

continuity  of,  347 
Neuroglia,  334 
Neurokeratins,  119,  281 
Neuro-muscular  junction,  204,  310 

spindles,  672 
Neuron,  definition  of,  332,  338 
Neurons,  continuity  of,  332 

structure,  333 
Neuropilem,  333 
Neutrophile  leucocytes,  918 
Nicol's  prism,  56 

Nicotine,  eifect  on  end-plates,  312 
on  heart,  1062,  1092 

method,  527 
Ninth  nerve,  nucleus  of,  426,  467 
Nissl's  granules,  337 
Nitrates,  43 

Nitrification  of  sewage,  43 
Nitrifying  organisms,  43 
Nitrogen,  42 

in  food,  686 

excretion  in  starvation,  704,  708 

estimation  of  by  KjeldoM's  method, 
1258 

endogenous,  in  urine,  856 

exogenous,  in  urine,  856 

output,  854 

requirements  of  body,  708 

source  of,  42 
Nitrogenous  constituents  of  urine,  855 

equilibrium,  688,  706,  732 
Nociceptive  stimuli,  386 
Nodal  point,  590,  593 
Noetid  vital,  1201 
Non-polarisable  electrodes,  251 
Normoblasts,  942 
Nuclear  sap,  17 
Nucleic  acid,  112,  113 
Nuclein,  107,  112 

hydrolysis  of,  874 

metabolism  of,  874-883 
Nucleins,  fate  of,  877 

formation  in  body,  877 
Nucleolus,  17 
Nucleoplasm,  17 
Nucleoprotein,  decomposition  of,  113 

digestion  of,  116 
Nucleus,  14,  29,  33 

ambiguus,  427 

of  Bechterew,  429,  454 

branched,  33 

caudatus,  410 

cuneatus,  413 

emboliformis,  420 

effect  of  removal,  31 


Nucleus,  fastigii,  420 

function  of,  29 

globosus,  420 

gracilis,  413 

lenticularis,  410 

necessity  for  growth,  33 

of  Luys,  425 

of  Rolando,  413 

relation  to  cytoplasm,  29 

structure  of,  16 
Nutrition,  mechanisms  of,  685,  914 

'Occipital  lobe,  473 
Occipito-frontal  fasciculus,  481 
Oculo-motor  nucleus,  426,  460,  463 
Oecoid,  925 
(Esophagus,  inhibition  of,  in  swallowing 

762 
(Estrus,  1371 

Ohm's  law  of  auditory  analysis.  568 
Oleic  acid,  60,  61 
Oleyl- lecithin,  63 
Olfactie,  561 
Olfactometer,  561 
Olfactory  apparatus,  475 

area.  506 

bulb.  476 

glomeruli,  476 

lobe,  473,  506 

mucous  membrane,  559 

sensations,  555.  560 

tract,  476 

tubercle,  476 
Olivary  body,  413,  415,  431 
Olive,  413,  415,  431 
Olivo-cerebellar  fibres,  438 
Olivo-spinal  tract,  399,  440' 
Oncometer,  1117 
Optic  axis,  590 

chiasma.  436,  459 

disc,  625 

nerve,  decussation,  436,  459 
efferent  fibres  in.  625 

radiation,  478,  479 

thalamus,  410,  423,  431,  444,  475 
nuclei  of,  424 

tracts,  436,  459,  504 
Optical  activity,  56 

axis  of  lens,  588 

centre  of  lens,  588 

defects  in  eye,  594 

isomers,  action  of  ferments  on,  186 
Optimum  temperature  for  ferments,  178 
Opsonic  index.  1160 
Opsonins,  1160 
Ophthalmometer,  602 
Ophthalmoscope,  617-619 
Optograms,  629 
Ora  serrata,  626 

Orcin  reaction  for  pentoses,  66,  104 
Organ  of  Corti,  574 
Organic  compounds  in  body,  49 
Organic  sensations,  669-681 
Organic  synthesis,  mechanism  of,  12l 
Organisation,  7 
Ornithine,  87,  92 

decarboxylation  of,  173 


INDEX 


1413 


Ortho  position,  54 
Onamines,  68 
Osazones,  52,  08,  1254 
Osmometer,  158,  159 
Oamotic  pressure,  137,  147 

Ii(ir(jtr\'i  method,  143         * 
Btcknmnn'ts  method,  143,  144 
and  boiling  point.  143 
i>[  colloids,  15!) 
of  electrolytes,  141 
freezing-point  method,  143 
by  hiemolysis,  141 
Hiimburgtr''s  method,  141 
measurement  of,  138-143 

by  plasmolysis,  140 
of  proteins,  83,  158 
of  serum  proteins.  158 
and  transport  of  water,  148 
and  vapour  tension.  143 
(Jssoous  labyrinth,  573.  075 
Osteoporosis,  700 
(Jtic  ganglion,  528 
Otolith  organ,  449,  676,  080 
Otoliths,  function  of,  680 
Outer  cell  lamina  of  cortex,  483 
Outer  fibre-lamina  of  cortex,  483 
Outer  line  of  BaiUarger,  486 
Overtones,  564 
Overton's  theory,  24 
Ovulation,  1366 
Ovum,  1347 

maturation  of,  1352 
(Jxahite  crystals,  1257 
Oxidases  in  tissues.  1237 
Oxidation,  174,  1186,  1233-1239 
by  indigo,  179 
mechanisms  of,  1233-1239 
seat  of,  in  body,  1186 
Oxyacids,  53 

origin  of,  860 
Oxygen,  42 

absorption  of,  in  lungs,  1185 

'  active,'  1235 

avidity  of  tissues  for,  1186 

capacity  of  blood.  1178 

effect  of  changes  in  tension  of,  1226 

lack,  in  asphyxia,  1107 

production  of  lactic  acid  in,  1210 
tension  in  alveoli,  1185,  1194 
in  blood,  1194 

in  blood  by  CO  method,  1198 
Oxyhiemoglobin,  927 

absorption  spectrum  of,  930 
crystals,  928 
dissociation  of,  1182 
influence  of  acids  on  reduction  of,  1186 
poxy  phenyl  alanine,  93 
Oxyprolino,  94,  95 

Pacinian  corpuscles,  554 

Pain  impulses,  path  of  in  cord,  404 

sense,  551 
Palmitic  acid,  59 
Pancreas,  ijiternal  secretion  of,  912 

structural     changes     accompanying 
secretion.  798 

extirpation  of,  910 


Pancreatic  diabetes,  910 
fistula,  795 
juice,  788 

action  on  carbohydrates,  793 
fats,  794 
milk,  793 
proteins,  789 
activation  of,  792 

by  calcium  salts,  793 
composition,  789 
secretion  of,  795 
variations  in,  798 
secretion,  effect  of  acids  in  duode- 
num, 796 
regulation  of,  798 
secretin,  797 
Pangene,  21 
Para  position,  54 
Parabanic  acid,  879 
Paracasein,  1387 
Paracentral  lobe,  473 
Paradox  cold,  545 
Paradoxical  contraction,  318 
Paraffins,  49 
Paraglobulin,  108 
Paramoecium,  conjugation  of,  1343 
Para  mucin,  117 
Paramyosinogen,  108,  238 
Paranuclein,  111,  772 
Paraplasm,  17 

Parathyroids,  functions  of.  1320 
Parietal  lobe,  473 
Parotid  gland,  743 

innervation  of,  740 
Parthenogenesis,  1355 
Partition  coefficient,  25 
Parturition,  1381-1383 

nervous  mechanLsm  of,  1383 
Passive  movement,  671 
Pawlow's  gastric  fLstuIa,  773 
Pelvic  visceral  nerve,  528 

action  on  bladder,  1295 
Pendular  movements  of  intestine,   817, 

818 
Pendulum  myograph,  218,  219 
Pentachromic  vision,  648 
Penta methylene  diamine,  173 
Pentosanes,  66.  118 
Pentoses,  66,  116 
Pentosuria,  06 
Pepsin,  action  of,  768 
Peptone,  food  value  of,  722 
Peptones,  111 

fractionation  of,  769 
Peptonised  blood,  948,  958 
Pericardium,  use  of,  1008,  1025 
Perilymph,  573 
Perimeter,  028 

Peripheral  ganglia,  inhibition  in,  531 
nerve  nets.  523 
reflexes,  529 
Peripolar  zone,  302 
Peristalsis.  819 

Permeability  of  membranes,  24,  140 
Peroxidases,  1237 
Pes.  421 
Pettenkojtrs  respiration  apparatus.  091 


1414 


INDEX 


Pfeffer's  cell,  138 

Pfluger's  law,  300 

Phagocytes,  1145 

Phagocytosis,  921,  1145 

Phakoseope,  600 

Phenylalanine,  94,  100 

Phenylethylaniine,  173 

Phenj'lglucosazone,  69 

Phenylhydrazme  test,  1254 

Pile nj'Uactosa  zone,  74 

Phenylmaltosazone,  74 

PMoridzin  diabetes,  905 

Phloroglucin  reaction  for  pentoses,  66 

Phonation,  pressure,  582 

Phosphates,  estimation  of,  1263 

excretion  in  large  intestine,  815 

by  kidney,  1283 
in  urine,  1243 

Phosphatides,  62 

PhospholipLnes,  62 

Phosphoprotem,  111 

Phosphoproteins,  action  of  gastric  juice 
on,  771 

Phosphorus,  47,  63 

Photochemical  substances  in  retina,  632 

Photo-hsematachometer,  1002 

Phototaxis,  29 

Phrenic  nerve,  electrical  variations  in,  269 

Phrenology,  491 

Phyllocyanin,  937 

Phylloporphyrin,  936 

Physiology,  definition  of,  1,  8 
general,  13 

Physiological  heat -values,  694 

Pick  on  fractionation  of  proteoses,  770 

Picric  acid,  55 

Pilomotor  nerves,  523 

Pineal  gland,  1334 

Pinna,  function  of,  569 

Piqure  diabetes,  904 

Pituitary  body,  extirpation  of,  1332 
structure  of,  1330 
extract,  effect  of,  1333 

Placenta,  functions  of,  1378 

Plain  muscle,  200,  271 

chemical  stimulation  of,  274 
contraction,   time -relations    of, 

271 
double  innervation  of,  276 
influence  of  temperature  on,  275 
mechanical  stimulation  of,  274 
stimulation  of,  272 

Plasma,  muscle- ,  237 
blood,  916,  975 

Plasmahaut,  23 

Plasmolysis,  23,  24,  140 

Plasmosome,  17 

Plasome,  21 

Plasteins,  188 

Plastids,  17,  35 

Plethora,  1129 

Plethysmograph  for  kidney,  1117 

Pleura,  1163 

permeability  of,  150 

Pleural  cavity,  negative  pressure  in,  llfiO 

Pneumogastric  nerve,  see  Vagus 

PofiVs  reverser,  209 


Poikilothermic  animals.  1308 
Polar  bodies,  1352 
Polar  zone,  302 
Polarimeter,  56 
Polarisation,  193,  251 
Oby  colloids,  161 

in  nerve,  315 
Polarised  light,  56 
Polarising  current,  297 
Polymorphonuclear  leiicocytes,  918 
Polvmorphous  layer  of  cortex,  484 
Polypeptides,  98,  99,  110,  790 

action  of  trypsin  on,  99 

reactions  of,  99 

synthesis  of,  97 
Polysaccharides,  67,  74 

Varolii,  418 
Pons,  antero -lateral  tract,  419 

functions  of,  443 

pedal  portion,  419 

structure,  417 

tegmentum,  419 
Portal  system  in  birds,  859 
Position,  sensations  of,  674-681 
Positive  after-images,  637 

polarisation  of  nerve,  317 

ventilation,  1217 
Posterior  columns  of  cord,  399 

crico-arytenoid  muscle,  580 

longitudinal  bundle,  415,  417,  419, 
429,  438,  461 

root-ganglion,  development,  336 
Postganglionic  fibres,  527 
Postural  reflexes,  507 

tonus,  507 
Potassium,  47 

Potential  energy  of  compounds,  1 74 
Precipitms,  1158 
Precuneus,  473 
Preganglionic  fibre,  526 
Pregnancy,  1376-1381 
Pre-pyramidal  tract,  399 
Presbyopia,  609 
Pressor  leflexes,  1126 
Pressure  impulses  in  cord,  404 

sense,  545 

slope  in  vascular  sj'stem,  990 
Primary  coil,  211 

colours,  644 
Primitive  sheath  of  nerve,  281 
Primordial  follicles,  1366 

utricle,  14,  140 
Principal  focus  of  lens,  588 

plane,  590 

point,  590,  593 
Projection  fibres  of  cerebrum,  477 
Projicient  sense  organs,  330,  432 
Proline,  94,  100 

fate  of,  872 
Pro-nuclei,  1352 
Prooestrum,  1371 
Prophase  of  mitosis,  1348 
Propionic  acid,  53,  59 
Proprioceptive  system,  447,  534,  669 
Propriospinal  fibres,  396 
Pro-secretin,  797 
Prostate,  1365 


INDEX 


U15 


Prosthetic  group,  112 
Piotamiuos,  102,  107,  112 
i'rotcctivo  colloids,  Kifi 
Protein,  absorption  of,  8:{i> 

action  of  nitrous  acid  «n,  98 

adsorpti(.n  by,  '!),  81 

alkaloidal  reactions,  10') 

amide  nitrogen  in,  101 

ammonia  nitrogen  in,  101 

amount  of  nitnim  ii  in,  088 

biuret  reaction,  102 

distribution  of  nitrogen  in  molecule, 

101 
effect  of,  on  metabolism,  700,  731 
effects  of  variation  in  diet,  708 
fractional  salting,  107 
hydrolysis  by  inzymcs,_84 
mmimum  requirement,  732 
osmotic  pressure  of,  83 
oxidation  of,  803 
salting  out,  100 
copper  compounds,  82 
hydrolysis,  83,  109 
metabolism,  854-873 
endogenous,  860 
in  starvation,  704,  708 
Folin's  theory,  721 
Pfliiger's  theory,  719-720 
Voit's  theory,  718 
molecule,   obscuio   eonstitumts    of, 
90 
structure  of,  b3,  97 
synthesis  of,  97 
precipitation  by  metallic  salts,  105 
Proteins,  49,  78 

carbohydrate  radicle  in,  104 
classification  of,  107-120 
colour  reactions  of,  102 
composition  of,  78,  100 
conjugated,  112 
constitution  of,  100 
crystallisation  of,  79 
derivatives  of,  109 
diamino-nitro.nen  in.  101 
dismtegration  products  of,  89 
halogen  derivatives,  109 
heat  coagulation  of,  79,  105 
hydrated,  109 
molecular  weight  of,  81 
monoamino-nitrogen,  101 
pliysieal  characters,  79 
putrefaction  of,  84 
salts  of,  79 
separation  of,  105 
specific  dynamic  effect  of,  711 
sulphur  in,  81 

synthesis  of  in  body,  120-132 
tests  for,  102 
as  colloids,  79,  105 
in  urine,  1253 
Proteose,  food  value  of,  722 
Proteoses,  111 

fractionation  of.  70'.> 
hydrolytic  proilucts,  70!) 
Prothrombin,  952 
Protocerebruni,  331 
Protopathic  sensibility,  652 


Protoplasm,  15,  10,  18 
AUmuniiH  theory,  18 
alveolar  theoiy,  19 
constituents  of,  39 
fibrillar  theory,  18 
gramdar  theory,  18 
hyaline.  18 

physical  condition  cf,  21 
salts  of,  47 

surface  tension  in,  22,  20 
theories  of  structure,  18 
varieties  of,  10,  18,  39 
ultra-microscopic  structure,  20 
Proximate  constituents  of  the  body,  49 
Psaherium.  482 
Pseudo-globulin,  977 
Pseudo-ions,  105-100^_ 
Pseudo-nuclein,  lU,  772 
Pseudo-reflexes,  529 
Pseudo-solution,  154 
Pseudomucin,  117 

Pseudopodia,  14  ... 

Psychical     secretion    of     gastric     juicc. 

775 
Ptyalin,  741 

Puberty,  changes  at,  1301 
Pulmonary  circulation,  1053- lOoO 

ventilation,  1170 
Pulse,  1034-1040 

anacrotic  wave,  1042 
catacrotic,  1042 
clinical  features  of,  1040 
dicrotic  wave,  1037,  1040,  1041 
Frank's  work  on,  1043 
in  veins,  1051 
percussion  wave,  1040 
peripheral,  1045 
pre-dicrotic  wave,  1040 
primary  wave,  1040 
qualities  of,  1040 
tidal  wave,  10_40 
Pulse- pressure,  987 
Pulse-rate,  in  man,  1098 

effect  of  oxygen  on,  1228 
Pulse- wave,  velocity  of,  1039 

nature  of,  1034 
Puh  inar.  424 
Pupil,  004 

contraction  of.  012 
dilatation  of,  014 
Purine  bases?,  H^     _      ' 
in  fieces,  852 
in  urine,  880 
metabolism,  874-883 
ring,  114,  875 
Piirkinjc  cells  of  cerebellum.  451 
fibres  of  heart,  1072 
figures,  027 
Purposive  reactions,  389.  444 
Putrefactive  amines,  173 

bacteria.  173 
Putrescine,  173 
Pyloric  canal,  783 
sphincter.  785 
vestibule,  783 
Pylorus,  nervous  mechanism  for  opening, 
785 


1416 


INDEX 


Pylorus,  opening  of,  783 

by  acid,  784 
Pyramidal  cells  of  cortex,  483 
decussation.  398,  412 
tracts,  397,  413,  479 
Pyrimidine,  115 
bases,  876 
nucleus,  115 
Pyrogallol,  55 
Pyrrol  ring,  94 

synthesis  of.  130 
a-pyrrolidin  carboxylic  acid,  94 
Pyruvic  acid,  53,  86 1 
origin  of,  861 

QUADRI-URATES,   1249 

Quellimg,  168 

Racemic  compounds,  57 
Radius  of  curvature,  formula  for,  601 
Rami  communicantes,  522 
Rdnvier's  nodes,  281 
Reaction,  bimolecular,  181 
monomolecular,  181 
velocity  of,  180,  181 
of  degeneration,  303 
time,  515 

methods,  517 
reduced,  516 
variation  of,  518 
for  hearing,  518 
for  sight,  518 
Reactions,  balanced,  185 

reversible,  185,  188 
Recapitulation,  Law  of,  13 
'  Receptor  '  substance,  312 

action  of  adrenalin  on,  314, 1324 
Recessive  characters,  1359 
Reciprocal  innervation  from  cortex,  494 
of  antagonistic  muscles, 
379 
Recording   instruments,  inertia  of,  220, 

1009,  1011 
Recti  muscles,  653 
Red-blindness,  646 

corpuscles,  net  Blood 
marrow,  941 
nucleus,  425,  431 
'Red  reflex'  618 
Reduced  eye,  593 
Reduction,  174 
Referred  pain,  531 
Reflex  action,  Bahnung,  344 
block  in,  343 
delay  in,  341 
facilitation  of,  344 
fatigue  of,  343,  388 
general  characters  of,  341 
inhibition  of,  344 
in  spinal  animal,  372,  374 
isolation  of,  385 
localisation,  341 
rebound,  388 
reinforcement,  385 
resistance,  343 

successive  spinal  induction,  388 
summation,  342 


Reflex  arc,  198,  333 
fatigue,  388 
inhibition,  383 
movements,  197 
scratch-,  387 
time,  342 
tone,  448 
Reflexes,  antagonistic.  387 
prepotency  of,  387 
reinforcement  of,  385 
scratch  area,  387 
Refraction  at  surfaces,  590 
in  schematic  eye,  591 
Refractive  indices  in  eye,  592 
Refractory  period,  306,  307 
Regnmdt  and  Reisefs  respiration  appa- 
ratus, 690 
Reissner's  membrane,  574 
RemaFs  ganglion,  1058,  1060 
Renal  excretion,  1240-1298 
mechanism,  1285-1288 
Rennin,  772 

Reproduction,  1341-1393 
in  man,  1361-1393 
in  metazoa,  1344 
in  protozoa,  1342 
Reproductive    organs,    development    of, 
1361 
female,  1366 
male,  1364 
Residual  air,  1170 
Resonants,  586 
Resonators,  565 
Resorcinol,  55 
Respiration,  1162-1239 

apparatus,  Benedict's,  690 
Haldane's,  689 
Pettenkofer's,  691 
Regnault  and  Reiset,  690 
Zuntz  and  Oeppert,  692 
chemistry  of,  1172-1199 
effects  of  changes  in  air  on,  1225-1232 
effect  on  circulation,  1054 
of  deghitition  on,  764 
of  division  of  vagi,  1215 
rate  of,  1164 

reflex  regulation  of,  1214-1224 
movements,  co-ordination  of,  1200 
'  Respiration  of  swallowing,'  760 
Respiratory  centre,  1201 

automaticity  of,  1202; 
chemical      excitants    of, 

1203-1205,  1213 
i  nhibitory  action  of  vagus 

on  1218 
spinal,  1202 

stimulation  of,  by  acids, 
1213 
by  oxygen  lack, 
1208 
exchange,  total,  689 
movements,  chemical  regulation  of, 
1204-1214 
Head's  method,  1215 
mechanics  of,  1162-1171 
regulation  of,  1200-1224 
muscles,  1166 


INDEX 


UlT 


Respiratoiy  quotient,  716,  1172 

^  effect  of  foods  on,  '  i ' 

in  diabetes,  9 13 
in  hibernation,  897 
in  muscular  work,  244 
sounds,  1108 
Restiform  body,  414,  4o3 

fibres  in,  41  ( 
Rete  raucosum,  1299 
Reticulin,  118 

Retina,  cliemical  changes  in,  b-' 
development  of,  622 
physical  changes  in,  629 
structure  of,  623  n^.y  n..o 

Retinal  changes  in  vision,  b22-b^d 
image,  path  of  rays,  o93 
induction,  649 
Retractor  lentis,  611 
Retractor  penis  muscle,  //o,  i^/* 
Retrograde  degeneration,  3b  1 
Reverser,  PoldS,  209,  210 
Reversibility  of  ferment  action.  ISo,  !»/ 

of  lipase,  188  _ 
Revertose,  185,  187 
Rheocord,  214 
Rheonome,  304 
Rheoscopic  frog,  262 
Rheotaxis,  1373 
Rhine ncephalon,  470 
Rhodopsin,  623,  629 
Rhombencephalon.  408 
Rhythm  of  heart,  1061 
Ribs,  movements  of,  1165 
Ricin,  1153 

Rigor  mortis,  233,  239 
Rima  glottidis,  579 
Ringer^s  fluid,  1080 
Rilttr-Valli  law,  309 
Riva  RoccVs  sphygmomanometer,  98/ 
Rod  cells,  623 

function  01,  641 
Rods  of  Corti,  574 
Rolandic  fissure,  473 
Roof  nuclei  of  cerebellum,  431,  4o3 
Rubro-spinal  tract,  399,  438 
RiiffinVs  organs,  554 


Saccharic  aciil,  68 

Saccharose,  73 

Saccule,  573  _ 

Saccus  endolymphaticuB,  690 

Sacral  autonomic  fibres,  528 

Salicylic  acid,  55 

Saliva,  composition  of,  /4U 

energy  involved  in  secretion,  too 
secretion  of.  742  ^ 

effect  of  nerves  on,  /4b 
Salivary  secretion,   energy  changes  m, 
755 
effect  of  metabolites,  7 jb 
histological  changes  in,  751 
pressure,  748 
theories  of,  748 

Salivary  digestion,  741 

in  stomacn,  i*^ 

fistula,  744 

glands,  innervation  of,  /4;) 


Salivary  glands,  changes  accompanying 
secretion,  748- /o4 
double  nerve-supply,  7o4 
electrical  changesl.in,  dunng 
secretion,  753 
Salmin,  coinpjsition  of,  100 
Salt  hunger,  725 

solutions,  absorbability  of,  832 
Salts,  absorption  of,  82(5 
Saponification.  51,  61 

number,  61 
Sarcolactic  acid,  240 
Sarcolemma,  199 
Sarcomere,  199 

structure  of,  203 
Sarcoplasm,  199 
Sarcosine,  93 
Sarcostyles,  199,  201 
Sarcous  elements,  201 
Sartorius  of  frog,  204,  207 
Scala  media,  573 

Scatol,  fats  of,  870  ,       ,•  „      oa"} 

Schdfers    theory    of    contraction,     203. 

265 
Scheiner's  experiment,  Go9 
Schematic  eye,  591 
Schlemm,  canal  of,  604 

functions,  666 
Schwann's  sheath,  280 
Sehleroproteins,  118 
Sclerotic  coat  of  eye,  603 
Scratch  reflex,  375 
Sebaceous  glands,  iciui 
Sebum,  13U1 
Second  focal  plane,  o90 
principal  focus,  o90 
wmd,  1101 
Secondary  coil,  211 
contraction,  262 
focus,  588 
tetanus,  262 
Secretin,  797,  1318 

action  on  intestmal  secretion,  810 

liver,  805 
extracted  by  soap,  797 
energy  changes  in,  /55 
stability  of,  797  _ 

Secretion,  energy  changes  _in,  ,oo 
Semicircular  canals,  4o0,  oi6 

destruction  of,  6/  < 
functions,  676 
SemUunar  ganglion,  522 

valves,  structure  of,  lOUb 
Semi-permeable  cell,  139 

membranes,  13»,  i*' 
Sensation,  extent  of  stimulus,  o38 
localisation  of,  536 
modality  of,  535 
phvsiology  of,  .>33-b81 
projection  of,  536  _ 

quantitative  study  of.. >3/-^.41 

relation  to  stimulus,  o^;i-^^ 
Sensations,  organic.  6_69-b81 
Sensori-motor  areas.  oOO 
Sensory  adaptation.  o38 

aphasia.  512 

areas  of  cortex,  501 


U18 


INDEX 


Sensory,  association,  509 

functions,  localisation  in  cortex,  501 

paralysis,  390 

path,  403 
Septo-marginal  bundle,  399 
Serine,  90,  100 
Serous  salivary  glands,  743 
Sertoli,  cells  of,  1365 
Serum-albumin,  108,  976 

composition  of,  100 
crystallisation  of,  80 
Serum-globulin,  108,  977 
Serum-proteins,  osmotic  pressure  of,  158 
Seventh  nerve,  nucleus  of,  427,  429,  467 

visceral  fibres,  527 
Sexual     organs,     relation     to     ductless 
glands,  1363 

process,  essential  features  of,  1341- 
1355 
Sham  feeding,  773 
Shock,  345 

spinal,  372 
Shooter  myograph,  219 
Short  ciliary  nerves,  615 

circuiting  key,  209 

sight,  594 
Sibilant  consonants,  586 
Side-chain  theory,  1156 
Side  wire,  Helmhollz,  211 
Silicon,  47 

Simultaneous  contrast,  651 
Sino-auricular  node,  1072 
Sino-spiral  fibres  of  heart,  1005 
Sinus  venosus,  in  eye,  604 
Sixth  nerve,  nucleus  of,  426,  464 
Size,  illusions  of,  661 

judgment  of,  659 
Skin,  absorption  bj',  1304 

corium,  1299 

functions  of,  1299-1304 

gaseous  exchanges  in,  1304 

papillae,  1300 

structure  of,  1299 
Small  intestine,  absorption  from,  826 
innervation  of,  820 
lymph  production  in,  828 
movemiuts  in,  817-825 
segmenting  movements  of,  818 
Smell,  sense  of,  559 

sensations,  555,  560 
Smooth  muscle,  see  Plain  muscle 
Snellen'. s  test  type,  596 
Soaps,  51,  61 

in  digestion,  836 
Sodium,  47 
Solar  I  lexus,  522 
Solar  spectrum,  635 
Sole  plate,  204 
Solidity,  judgment  of,  662 
Sols,  154 

Soluble  casein,  772 
Soluble  starch,  75 

Solubility  of  gas,  effect  of  pressure  on,  11 79 
Solute,  145 
Somatic  cells,  1345 
Somatic  nervous  system,  520 
Sorbite,  68 


Sound,  nature  of,  562 
pitch  of,  563 
timbre,  563 

Soimd-waves,  amplitude  of,  563 
compound,  565 

Spaces  of  For.tana,  604 

Spastic  gait,  379,  508 
paraplegia,  379,  508 

Specific  dynamic  action  of  proteins,  711, 
863,  907 
irritability,  law  of,  286 

Spectacles,  use  of,  595 

Speech,  511,  578-586 

intellectual  basis  of,  513 
mechanism  of,  584 

Spermaceti,  61 

Spermatids,  1350 

Spermatocytes,  1350 

Spermatozoa,  development  of,  1350 

Spermatozoon,  1347,  1351 

Spherical  aberration,  597 

Sphincter  pupUlse,  612 
trigoni,  1290 
urogenitalis,  1291 

Sphingomyeline,  62 

Sphvgmographs,  1038 

'  Spike  '  tracing,  analysis  of,  258,  260 

Spinal  animal,  372,  442 

Spinal  cord,  afferent  path,  370 

anterior  cerebellar  tract,  401 

columns,  401 
ascending  tracts,  397,  399 
Burdaclis  column,  366 
cells  in,  359 

of  columns,  359 
central  canal,  337 
Clarke's  columns,  359 
collaterals  in,  366,  396,  403 
comma  tract,  399 
commissural  cells,  359 
conduction  in,  396-406 
crossed  pyramidal  tract,  398 
descending  tracts,  397 
development,  336 
direct  cerebellar  tract,  401 

pyramidal  tract,  398 
dorsal  cerebellar  tract,  401 
effect  of  poisons,  392 
efferent  path,  369 
endogenous  fibres,  398 
Golgi  cells,  359 
Golls'  column,  367 
Gower's  tract,  401 
Helweg's  bundle,  399 
-""^    hemisection,  404 

lateral  basis  bundle,  417 
lateral  columns,  401 
Lissauer's  tract,  366,  398,  403 
Marie's  tract,  399 
Monakow's  bundle,  399 
motor-cells,  359 
olivo-spinal  tract,  399 
pain  impulses,  404 
path  of  impulses,  402 
posterior  columns,  399 
postero-external  column,  366 
pre-pyramidal  tract,  399 


INDEX 


lil9 


Spinal  cord,  pyramidal  tracts,  397 
as  reflex  centre,  304 
lubro-spinal  tract.  3!K) 
serisori-inotor  pith,  403 
scpto-jnarjjiiial  bundle,  399 
structure,  35") 
thalamico-spinal  tract,  399 
tracts,  methods  of  traciiig,  3r)9 
ventral  cerebellar  tract,  401 
vestibulo-sjjinal  tract,  399 
W'allerian  degeneration,  397 
wliite  matter,  arrangement,  397 
Spinal  dog,  374 
shock,  372 
Spino-tectal  tract,  401 
Spuio-thalamic  tract,  401 
Spiral  ganglion,  575 

lamina,  575 
Spireme  stage  of  mitosis,  1348 
Splanclinic  motor  nuclei,  427 
nerve,  1120 
sensory  nuclei,  426 
system,  520 
Spleen,  function  of,  1336 

rhythmic  ccmtractions  of,  1335 
structure  of,  1335 
Spangin,  120 
Spongioblasts,  281,  335 
Spongio  plasm,  18 
Spring  myograph,  219 
Staining,  intravitam,  25 
Staircase  phenomenon,  274 

in  heart  muscle,  1075 
Stannius"  ligature,  1058 
Stapedius  muscle,  572 
Stapes,  571 
Starches,  75 

Starch,  digestion  by  saliva,  741 
hydrolysis  of,  75,  110 
inhibition  by,  169 
molecular  weight,  76 
soluble,  75 
structure  of,  76 
Starvation,  carbohydrate  metabolism  in, 
702 
fat  metabolism  iia,  705 
loss  in  various  organs,  700 
metabolism  in,  698-705 
protein  metabolism  in,  704,  708 
Static  ataxy,  391 
Stearic  acid,  59 
Stearjd-lecithin,  63 
Stellate  ganglion,  522 

layer  of  cortex,  483 
Stepping  reflex,  376 
Stereo  bilin,  origin  of,  804 
Stereoisomerism,  57,  65,  80 
Stereosomers,  action  of  ferments  on,  186 
Stereoscope,  663 
Stereoscopic  vision,  662 
Slernzdkn,  922 
Stimulation,  electrical,  nature  of.  304 

of  h\iman  nerve.  302 
Stimuli,  summation  of,  274 
Stimulus,  liminal,  538 

intensity  of,  538 
locus  of,  383 


Stimulus,  maximal  ,216,  230 
minimal,  216,  230 
subniiniinal,  216 
tlireshold,  338 
Stokes- Adums  disease,  1072 
Stomach,  digestion  in,  766-781 
innervation,  786 
movements  of,  782 
secretory  nerves  of,  775 
sphincters,  785 
Storage  battery,  208 
Stratum  granuiosum,  1299 

lucidum,  1299 
Stria  terminalis,  424 
Striaj  acousticse,  427,  428 
Striated  muscle,  structure  of,  109 

of  invertebrates,  277 
String  galvanometer,  255 
Stroma  iche,  1026 
StroMuhr,  Ludwig's,  1001 

Starling -s,  1001 
Structural  basis  of  body,  13 
Strychnine,  effect  on  cord,  392 

spasm,  electrical  variation,  209 
Sturin,  composition  of,  100 
Sublingual  gland,  743 
Submaxillary  ganglion,  527,  746 

gland,  743 
Subniaximal  stimulus,  216 
Subminimal  stimulus,  216 
Substantia  gclatinosa  of  Rolando,  358 

nigra,  421,  425,  431 
Substrate,  183 

effect  of  ferments  on,  186 
Subthalamic  region,  425 
Successive  contrast,  650 

spinal  induction,  388 
Succus  cntericus,  see  Intestinal  juice 
Sugar  in  urine,  1253 

formation  of,  from  fat,  896 

from  protein,  1253 
in  plants,  123 
utilisation  of,  in  body.  002 
Sugars,  chemistry  of,  67-74 

oxidisability  of,  in  body,  1234 
Sulphocyanate  in  saliva,  741 
Sulphocyanates,  orighi  of,  741 
Sulphur,  45 

excretion  of,  869 
test  for  proteins,  95,  104 
Summation,  273 

of  muscular  contractions,  226 
of  sensation.  538 
of  stimuli.  274,  306 

in  heart  muscle,  1075 
tones,  508 
Superior   cerebellar  ix'duneles.   decuBsa* 
tion  of,  422 
cervical  ganglion,  520 
uoriX)ra  quailrigemina,  funolione  of, 

401 
nusenteric  ganglion,  522 
oblique  muscle.  053 
olive.  413,  415.  431 
]H'dvnieles  of   cerebellum,   418,    422, 
438. 454,  478 
Supplemental  air,  117U 


1420 


IM)EX 


Suprarenal  bodies,  1320-1325 

development  of,  1321 
Surface  tension,  22,  26 

in  colloids,  157 
theory,  265 
Suspensory  ligament,  604 
Swallowing — see  Deglutition 
Sweat,  amount  and  properties,  1302 

glands,  1302 

loss  of  heat  by,  1314 

nerves,  1303 

secretion,  1303 
Swim-bladder  of  fish,  1198 

tension  of  oxygen  in.  149 
Sylvian  aqueduct,  409,  421 

fissure,  473 
Symbiosis,  1143 
Sympathetic  ganglia,  520 

functions,  529 
Sympathic  nerves  of  heart,  1087 

Tabes  dorsalis,  391 
Tach\-pnoea,  1204 
Tactile  localisation.  548 

sensation,  local  sign  of,  549 

sensations,  545 

sense  area,  503 
paths,  503 
Takadiastase,  187 
Talbot's  law,  638 
Tartaric  acid,  57 
Taste,  555 

area,  506 

buds,  556 

nerves  of,  558 

sensation,  classification,  556 
Tears,  composition  of,  664 
Tecto-spinal  tract,  440 
Tendril  fibres,  452 
Tenon,  capsule  of,  653 
Tension,  effect  of  on  bladder,  1294 
on  heart,  1077 
on  muscle,  232 
Tensions  of  gases  in  liquids,  1180 
Tensor  tympani  muscle,  572 
Tenth  nerve,  nucleus  of,  467 
Test  type,  596 
Testis,  structure  of,  1364 
Tetanus,  228 

toxin,  action  on  cord,  393 
Tetrachromic  vision,  648 
Tetrahedron  theory,  56 
Tetramethylene  diamine,  173 
Tetrapeptides,  99 
Tegmentum  of  pons,  419 

of  mid-brain,  422 
Teichmann's  crystals,  932 
Telencephalon,  409 
Telophase  of  mitosis,  1348 
Temperature,  action  of,  on  heart,  1079 
on  muscle,  233 

effect  of,  on  metabolism,  1306,  1311 
on  electrical    variations  in 
muscle,  257 

limits  of,  for  life,  6 

sense,  542 

adaptation  of,  544 


Temporal  lobe,  473 
Tempore- pontine  fibres,  480 
Tendon  phenomena,  377 
use  of,  380 

reflexes,  232,  377 
Thalamencephalon,  441,  444 
Thalamico-spiual  tract,  399 
Thalamo-cortical  tract,  477 
Thala mo-frontal  fibres,  478 
Thala mo- spinal  tract,  440 
Theca  externa,  1367 
Theobromine,  115,  875 
Thermo-electric  couple,  247 

junctions,  246 
Thermogenic  centres,  1316 
Thermopile,  246 
Thermotaxic  system,  1316 
Thigmotaxis,  28 
Thiophene  test,  241 
Third  nerve,  functions  of,  615 

nucleus  of,  426,  430,  460,  463 
visceral  fibres  in,  527 
Thiry-  Vdla  fistula,  808 
Threshold  stimulus,  539 

value,  538 
Thrombin,  950 
Thrombogen,  952 
Thrombokinase,  952 
Thymine,  llo,  876 

Thymus,  structinre  and  functions  of.  1334 
Thyroid  cartilage,  578 

extirpation  of,  1327 

extract,  effects  of,  1329 

structure  of,  1325 
ThjTO-arj'tenoid  ligaments,  579 

muscle,  581 
ThjTo-epiglottidean  muscle,  581 
Tidal  air,  1170 
Time-record,  217 
Tissue-fibrinogen,  113,  955 
Time-marker,  217,  220 
Tissue -proteins,  718 
Tone  in  muscle,  377 
Tonus,  postural,  507 
Tortoise  heart,  1058 
Touch  discrimination,  548 

impulses  in  cord,  404 

projection  of,  550 

sense,  545 

spots,  545 
Toxins,  adsorption  of,  1156 

bacterial,  1153 

mode  of  action,  1153 
Toxoids,  1157 
Toxones,  1155 
Toxophore  group,  1157 
Traube-Hering  curves,  1109 
Transformations  of  energy,  136 
Transudations,  coagulation  of,  958 
Trapezium  of  pons,  419,  428,  436 
Treppe  phenomenon,  see  Staircase 
Trichromats,  anomalous,  648 
Trichromatic  vision,  646 
Tricuspid  valve,  1006 
Trigeminal  nerve,  nucleus  of,  427 
Trigemino-thalamic  tract,  436 
Trigger  myograph,  219 


INDEX 


1421 


Trigonum  habenulae,  423 

Trimethylamine,  54 

Triolein,  00 

Tripalmitin,  00 

Tripeptides,  99  ,    infi? 

Triphasic  variation  of  heart,  10b7 

Triple  phosphate,  1244,  12o8 

Tristcarin,  00 

Tritocerebrum,  331 

Trommer's  test,  08 

Trophoblast,  1377 

Trvpsin»  ^^^  . ,       nni 

action  on  polypeptides,  791 

on  proteins,  /  89 
destruction  of,  791      _ 
velocity  of  action,  18jj 
of  reaction,  791 

TrvptopS,  94.  100,  104 

fate  of,  862 
Tuber  cinereum.  422 
Tuning-fork,  217,  220 
Turacin,  938  __ 

Tympanic  membrane^  o/O 

movements  of,  571 
Tympanum,  570 
Tyrosinase,  1237 
Tyrosine,  55,  93,  100,  101 

crystals.  93 

reactions.  94 

in  urine.  1257 

VffelmanvLS  reagent,  241 
Ultra-microscope,  61  _ 

U  tra-red  rays,  insensitivity  of  eye  to,  63o 
Ultra-violet  rays,  absorption  m  eye,  63o 
Umbilical  cord,  13 '8 
Uncinate  fasciculus,  481 

Uncus,  473  +i,  ^f  j. 

Unicellular  organisms,  growth  of,  4 
Unimolecular  reaction.  181 
Unipolar  excitation,  302 

law  of,  303 
Unstriated  muscle,  271 

propagation  of  wave  in,  2  /  •- 

UracU,  115,  876 
Urate  deposit,  1257 
Urates,  1249 
Urea,  1245 

estimation,  1259 

iTohn'*  method.  1260 

hypobromite  method,  U>>J 
fermentation  of,  1240 
origin  of,  857  ^ 

output  in  starvation,  /  04 

on  protein  diet,  8ob 
oxalate.  1246  . 

preparation  from  urine,  1-21/ 
Ureter,  contractions  of,  1289 
Uric  acid.  114,  124_8_ 
crvstals.  1257 
da"ily  amount.  1250 
endogenous,  880 
estimation.  1261 
excretion.  879 
in  gout.  882 
origin  of,  878 


Uric  acid,  oxidation  of,  879 
preparation,  1248 
production  in  birds,  8-59 
structure  of.  875 
synthesis.  114 
tests,  1249 
Uricolytic  ferment,  879 
Urinary     constituents,     estimation     of, 
1 258-1 263_ 
deposits,  12.57  i.i-.o 

Urine,  abnormal  constituents  m.    12..3- 
12.58 
acetone  in,  12.55  _ 
ammonia  in,  124.5 
average  composition,  Vl*^ 
bases  of,  1244 

on  various  diets,  8»0 
conditions  of  glomerular   filtration, 

1272 
freezing-point,  1241 

inorganic  constituents  of,  124/ 

lactose  in,  1253 

neutral  sulphur  in,  124-3 

organic  constituents  of,  V^AO 

oxyacidsin,  12.5.5 

specific  gravity  of,  1^41 

sugar  in,  12.53 

phosphates  of.  1243 

pigments  of,  12.52 

pressure  of,  in  ureter,  iJ.il 

reaction  of,  1241 

secretion  of,  1264-1288 
in  glomerulus.  126.) 
influenceof  colloids,  12// 

kidney  volume,  1274 

sulphates  of,  1243 
Uriniferous  tubule,  course  of,  1265 

tubule,  functions  of,  l/bS 
Urobilin,  1252  _ 
Uro  chrome,  12.52 
Uroerythrin,  1252 
Urorosein,  1253 

■       liCfohanS"  in,  .luring   pregnancy. 
1376 
nerve-supply,  1374 
Utricle,  573 

primordial,  14,  140 

Uvea,  626 

Vacuole,  contractile,  15 
food,  15  _ 

Vago'^guTssopharyngeal  nucleus,  426,  467 

Vagus.  528 

action  on  auricles,  1091 

on  bronchioles,  468 

on  heart.  1089 

on  intestines.  819 

on  oesophagus.  7l>4_ 

on  respiration.  1215 

on  stomach.  785 
distribution  in  abdomen,  <8b 
excitation.  Kngdmannii  views,  1091 
expiratory  fibres,  121o 


1422 


INDEX 


Vagus,  inspiratory  fibres,  1215 
nucleus  of,  467 

proof  of  inspiratory  fibres  in,  1219 
tonic  action  on  heart,  1094 
Valerianic  acid,  59 
Valine,  90 

Valve  of  Vieusscns,  409,  418 
Valves  of  heart,  see  Heart 
Variation,  monophasic,  257 
Vasa  afferentia.  1267 
etferentia.  1267 
recta,  1267 
Vascular  area  of  chick,  939 

system,  influence  of  capacity  of,  on 

circulation,  993 
tone,     effect     of     central     nervous 
system  on,  1103 
peripheral,  1113 
Vaso- constrictor  fibres,  course  of,  1119 
Vaso-dilatation,  criteria  of,  1116 

by  metabolites,  1128 
Vaso-dilator      fibres     in      nerve-trunks, 
1122 
nerves,  1121 
Vaso-motor  centre,   action  of  acids  on, 
1100.  1112 

location  of,  1104 
variations  in  activity  of,  1105 
centres  in  cord,  1111 
impulses,  path  of,  in  cord,  406 
nerves,  course  of,  1114 

experimental  methods 
influence  on  blood-pressure 
reflexes,  1126 
Vegetable  food,  utilisation  of,  726 
Vegetarian  diet,  726,  734 
Veins,  blood-flow  in,  1050-1052 
capacity  of,  996 
distensibility  of,  982 
structure  of,  982 
valves  in,  1051 
Velocity  of  reaction,  181 

in  vascular  system,  991 
Venous  pressure  in  man,  989 

outflow,  determination  of,  1119 
pulse,  1051 

in  heart  block,  1073 
Ventilation,  1231 
Ventral  cerebellar  tract,  401,  417 
Ventricle  of  Morgagni,  579 
Ventricles,  capacity  of,  1004 

pressure  in,  1009 
Ventricular  diastole,  1008,  1024 

systole,  1008 
Veratrine,  action  of,  on  muscle,  236 
Vesicle,  germinal,  1368 
Vesicular  murmur,  1169 
Vestibular  nerve,  Deiters'  nucleus,  429, 
454 
functions  of,  449 
median  nucleus  of,  429 
nucleus  of,  428,  466 
Vestibule,  573,  675 
Vestibulo-cerebellar  fibres,  417,  438 
Vcstibulo-spinal  tract,  399,  440 
Vibrative  consonants,  586 
Vicq  d'Azyr's  bundle,  437,  477 


Villus,    changes    in.    during    protein   ab- 
sorption, 840 
Villus,  structure  of,  827 
Viscera,  afferent  fibres  of,  531 

innervation  of.  528 

sensibility  of,  551 
Visceral  nervous  system,  520-532 
Vision,  587-668 

direct,  627 

indirect,  627 

single.  656 
Visual  adaptation,  639 

angle,  593,  659 

axis,  625 

centre,  504 

fatigue.  639 

judgments,  658-663 

localisation,  659 

path,  436,  459.  504 

purple.  623,  629 

reflexes,  459-462 

sensation,  Weher's  law,  637 

sensations,  634-652 

stimuli,  time  relations,  637 
Visuo-psychic  area,  lamination,  487 
Visuo-sensory  area,  lamination,  487 
Vital  capacity,  1170 
Vitalism,  9 
Vitellins,  111 
Vitreous  humoiir,  592 
Vocal  cords.  579 
Voice,  578-586 

in  singing,  583 

pitch  of,  584 

production  of,  581 

range  of,  582 
Volatile  fatty  acids,  61 
Volhard's  method  for  chlorides,  1262 
Voluntary  contraction,  266 

electrical  changes  in,  269 
record,  268 

muscle,  197 
Vowel  sounds,  584 

percussion  method,  585 

Wallerian  degeneration,  397 

method,  361 
Wagner's  hammer,  211,  212,  213 
Wandering  phagocytes,  922 
Warm  points,  543 
Water,  absorption  of,  826 

estimation  in  food,  686 

necessity  for,  7 

and   dissolved    substances,    passage 
across  membranes,  145-153 

rigor,  259,  1064 

vacuole,  15 
Weber's  law,  539,  548 

in  vision,  637 
Wernicke's  aphasia,  512 
Weyl's  test,  1247 
Wheatstone  bridge,  248 
White  rami,  522 

sensation  of,  ('43 
Whispering,  581 
Word- blindness,  514 
Work,  relation  to  stimulus,  28 


INDEX  1423 


Xanthine,  114,  878  Zincative,  2>7 

Xanthoproteic  reaction,  103  Zona  fasciculata.  1321 

Xylose,  66,  116  Zollner' s  VmcH,  661 

Zona  glomerulosa,  1321 
Yeasts,  action  on  amines,  84  pellucida,  1367 

on  carbohj'drates,  69,  70,  71,  74  reticulata,  1321 

Yellow  spot,  625  Zonula  cili  irin,  604 

Young-Helmholtz  theory,  645  Zonule  of  Zinn,  604 

Zooi.l,  925 
Zein,  109  Zymins,  753 

food-value  of,  723  Zymogen  granules,  753 


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